WO2004018497A2 - Modified nucleotides for polynucleotide sequencing - Google Patents
Modified nucleotides for polynucleotide sequencing Download PDFInfo
- Publication number
- WO2004018497A2 WO2004018497A2 PCT/GB2003/003686 GB0303686W WO2004018497A2 WO 2004018497 A2 WO2004018497 A2 WO 2004018497A2 GB 0303686 W GB0303686 W GB 0303686W WO 2004018497 A2 WO2004018497 A2 WO 2004018497A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- nucleotide
- group
- nucleotides
- allyl
- label
- Prior art date
Links
- 0 *CC(C(C1)O)OC1N(C=C(C(N)=N1)C#CCNC(C(F)(F)F)=O)C1=O Chemical compound *CC(C(C1)O)OC1N(C=C(C(N)=N1)C#CCNC(C(F)(F)F)=O)C1=O 0.000 description 4
- SUACIFPWPDVAEY-UHFFFAOYSA-N C=CCOC(C1)C(COP(O)(OP(O)(OP(O)(O)=O)=O)=O)OC1[n](cc1C#CCN)c2c1c(N)ncn2 Chemical compound C=CCOC(C1)C(COP(O)(OP(O)(OP(O)(O)=O)=O)=O)OC1[n](cc1C#CCN)c2c1c(N)ncn2 SUACIFPWPDVAEY-UHFFFAOYSA-N 0.000 description 1
- GCTLMRFFOCJNEQ-UHFFFAOYSA-N CC(C)(C)[Si](c1ccccc1)(c1ccccc1)OCC(C(C1)O)OC1[n](cc1C#CCNC(C(F)(F)F)=O)c(N=C(N)N2)c1C2=O Chemical compound CC(C)(C)[Si](c1ccccc1)(c1ccccc1)OCC(C(C1)O)OC1[n](cc1C#CCNC(C(F)(F)F)=O)c(N=C(N)N2)c1C2=O GCTLMRFFOCJNEQ-UHFFFAOYSA-N 0.000 description 1
- RDNQXASRTWMHCY-UHFFFAOYSA-N NC(N1)=Nc([n](C(C2)OC(CO)C2O)cc2C#CCNC(C(F)(F)F)=O)c2C1=O Chemical compound NC(N1)=Nc([n](C(C2)OC(CO)C2O)cc2C#CCNC(C(F)(F)F)=O)c2C1=O RDNQXASRTWMHCY-UHFFFAOYSA-N 0.000 description 1
- ULRPISSMEBPJLN-UHFFFAOYSA-N Nc1nnn[nH]1 Chemical compound Nc1nnn[nH]1 ULRPISSMEBPJLN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6869—Methods for sequencing
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2525/00—Reactions involving modified oligonucleotides, nucleic acids, or nucleotides
- C12Q2525/10—Modifications characterised by
- C12Q2525/186—Modifications characterised by incorporating a non-extendable or blocking moiety
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2535/00—Reactions characterised by the assay type for determining the identity of a nucleotide base or a sequence of oligonucleotides
- C12Q2535/113—Cycle sequencing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- the invention relates to modified nucleotides.
- this invention discloses nucleotides having a removable protecting group, their use in polynucleotide sequencing methods and a method for chemical deprotection of the protecting group.
- nucleic acids DNA and RNA has benefited from developing technologies used for sequence analysis and the study of hybridisation events.
- An example of the technologies that have improved the study of nucleic acids is the development of fabricated arrays of immobilised nucleic acids. These arrays consist typically of a high-density matrix of polynucleotides immobilised onto a solid support material. See, e.g., Fodor et al . , Trends Biotech .
- Fabricated arrays can also be manufactured by the technique of "spotting" known polynucleotides onto a solid support at predetermined positions (e.g., Stimpson et al . , Proc . Natl . Acad. Sci . USA 92:6379-6383, 1995).
- Sequencing by synthesis of DNA ideally requires the controlled (i.e. one at a time) incorporation of the correct complementary nucleotide opposite the oligonucleotide being sequenced. This allows for accurate sequencing by adding nucleotides in multiple cycles as each nucleotide residue is sequenced one at a time, thus preventing an uncontrolled series of incorporations occurring.
- the incorporated nucleotide is read using an appropriate label attached thereto before removal of the label moiety and the subsequent next round of sequencing.
- blocking group In order to ensure only a single incorporation occurs, a structural modification ("blocking group") of the sequencing nucleotides is required to ensure a single nucleotide incorporation but which then prevents any further nucleotide incorporation into the polynucleotide chain.
- the blocking group must then be removable, under reaction conditions which do not interfere with the integrity of the DNA being sequenced.
- the sequencing cycle can then continue with the incorporation of the next blocked, labelled nucleotide.
- the entire process should consist of high yielding, highly specific chemical and enzymatic steps to facilitate multiple cycles of sequencing.
- nucleotide and more usually nucleotide triphosphates, generally require a 3 OH-blocking group so as to prevent the polymerase used to incorporate it into a polynucleotide chain from continuing to replicate once the base on the nucleotide is added.
- a 3 OH-blocking group There are many limitations on the suitability of a molecule as a blocking group. It must be such that it prevents additional nucleotide molecules from being added to the polynucleotide chain whilst simultaneously being easily removable from the sugar moiety without causing damage to the polynucleotide chain.
- the modified nucleotide must be tolerated by the polymerase or other appropriate enzyme used to incorporate it into the polynucleotide chain.
- the ideal blocking group- will therefore exhibit long term stability, be efficiently incorporated by the polymerase enzyme, cause total blocking of secondary or further incorporation and have the ability to be removed under mild conditions that do not cause damage to the polynucleotide structure, preferably under aqueous conditions.
- These stringent requirements are daunting obstacles to the design and synthesis of the requisite modified nucleotides.
- Reversible blocking groups for this purpose have been described previously but none of them generally meet the above criteria for polynucleotide, e.g. DNA- compatible, chemistry.
- Metzker et al . ⁇ Nucleic Acids Research, 22(20): 4259-4267, 1994 discloses the synthesis and use of eight 3 '-modified 2-deoxyribonucleoside 5 ' -triphosphates (3 ' - modified dNTPs) and testing in two DNA template assays for incorporation activity.
- the 3 ' -modified dNTPs included 3'allyl deoxyriboadenosine 5 ' -triphosphate (3 ' - allyl dATP) .
- the Kamal deprotection methodology employs sodium iodide and chlorotrimethylsilane so as to generate in si tu iodotrimethylsilane, in acetonitrile solvent, quenching with sodium thiosulfate. After extraction into ethyl acetate and drying (sodium sulfate) , then concentration under reduced pressure and column chromatography (ethyl acetate :hexane; 2:3 as eluant) , free alcohols were obtained in 90-98% yield.
- the present invention is based on the surprising development of a number of reversible blocking groups and methods of deprotecting them under DNA compatible conditions. Some of these blocking groups are novel per se; others have been disclosed in the prior art but, as noted above, it has not proved possible to utilised these blocking groups in DNA sequencing.
- One feature of the invention derives from the development of a completely new method of allyl deprotection. Our procedure is of broad applicability to the deprotection of virtually all allyl-protected hydroxyl functionality and may be effected in aqueous solution, in contrast to the methodology of Kamal et al . (which is effected in acetonitrile) and to the other methods known generally in the prior art which are highly oxygen-and moisture-sensitive.
- a further feature of the invention derives from the development of a new class of protecting groups. These are based upon acetals and related protecting groups but do not suffer from some of the disadvantages of acetal deprotection known in the prior art .
- allyl deprotection methodology makes use of a water-soluble transition metal catalyst formed from a transition metal and at least partially water-soluble ligands. In aqueous solution these form at least partially water-soluble transition metal complexes.
- aqueous solution herein is meant a liquid comprising at least 20 vol%, preferably at least 50%, for example at least 75 vol%, particularly at least 95 vol% and especially greater than above 98 vol%, ideally 100 v ⁇ l% of water as the continuous phase.
- the allyl group may be used to protect not only the hydroxyl group but also thiol and amine functionalities.
- allylic esters may be formed from the reaction between carboxylic acids and allyl halides, for example.
- Primary or secondary amides may also be protected using methods known in the art.
- the novel deprotection methodology described herein may be used in the deprotection of all these allylated compounds, e.g. allyl esters and mono- or bisallylated primary amines or allylated amides, or in the deprotection of allylated secondary amines.
- the method is also suitable in the deprotection of allyl esters and thioethers .
- Protecting groups which comprise the acetal functionality have been used previously as blocking groups. However, removal of such groups and ethers requires strongly acidic deprotections detrimental to DNA molecules. The hydrolysis of an acetal however, results in the formation of an unstable hemiacetal intermediate which hydrolyses under aqueous conditions to the natural hydroxyl group.
- the inventors have utilised this concept and applied it further such that this feature of the invention resides in utilising blocking groups that include protecting groups to protect intermediate molecules that would normally hydrolyse under aqueous conditions. These protecting groups comprise a second functional group that stabilises the structure of the intermediate but which can be removed at a later stage following incorporation into the polynucleotide.
- a modified nucleotide or nucleoside molecule comprising a purine or pyrimidine base and a ribose or deoxyribose sugar moiety having a removable 3 ' -OH blocking group covalently attached thereto, such that the 3' carbon atom has attached a group of the structure
- the invention provides a 3'-0-allyl nucleotide or nucleoside which nucleotide or nucleoside comprises a detectable label linked to the base of the nucleoside or nucleotide, preferably by a cleavable linker.
- the invention provides a polynucleotide comprising a 3 ' -O-allyl nucleotide or nucleoside which nucleotide or nucleoside comprises a detectable label linked to the base of the nucleoside or nucleotide, preferably by a cleavable linker.
- the invention provides a method of converting a compound of formula R- 0-allyl, R 2 (allyl), RNH(allyl), RN (allyl) 2 or R-S-allyl to a corresponding compound in which the allyl group is removed and replaced by hydrogen, said method comprising the steps of reacting a compound of formula R-O-allyl, R 2 N(allyl), RNH(allyl), RN (allyl) 2 or R-S-allyl in aqueous solution with a transition metal comprising a transition metal and one or more ligands selected from the group comprising water-soluble phosphine and water- soluble nitrogen-containing phosphine ligands, wherein the or each R is a water-soluble biological molecule.
- the invention provides a method of controlling the incorporation of a nucleotide molecule complementary to the nucleotide in a target single- stranded polynucleotide in a synthesis or sequencing reaction comprising incorporating into the growing complementary polynucleotide a molecule according to the invention, the incorporation of said molecule preventing or blocking introduction of subsequent nucleoside or nucleotide molecules into said growing complementary polynucleotide.
- the invention provides a method for determining the sequence of a target single-stranded polynucleotide, comprising monitoring the sequential incorporation of complementary nucleotides, wherein at least one incorporation, and preferably all of the incorporations is of a nucleotide according to the invention as hereinbefore described which preferably comprises a detectable label linked to the base of the nucleoside or nucleotide by a cleavable linker and wherein the identity of the nucleotide incorporated is determined by detecting the label, said blocking group and said label being removed prior to introduction of the next complementary nucleotide.
- the invention provides a method for determining the sequence of a target single- stranded polynucleotide, comprising:
- nucleotides are preferably linked from the base to a detectable label by a cleavable linker and wherein the detectable label linked to each type of nucleotide can be distinguished upon detection from the detectable label used for other types of nucleotides;
- steps (e) optionally repeating steps (b) - (d) one or more times; thereby determining the sequence of a target single- stranded polynucleotide.
- the invention provides a kit, comprising: (a) a plurality of different individual nucleotides of the invention.
- the nucleosides or nucleotides according to or used - lo in the methods of the present invention comprise a purine or pyrimidine base and a ribose or deoxyribose sugar moiety which has a blocking group covalently attached thereto, preferably at the 3'0 position, which renders the molecules useful in techniques requiring blocking of the 3 ' -OH group to prevent incorporation of additional nucleotides, such as for example in sequencing reactions, polynucleotide synthesis, nucleic acid amplification, nucleic acid hybridisation assays, single nucleotide polymorphism studies, and other such techniques.
- blocking group is used herein in the context of the invention, this embraces both the allyl and “Z” blocking groups described herein.
- each "Z" group will generally be the same group, except in those cases where the detectable label forms part of the "Z" group, i.e. is not attached to the base.
- the molecule can be linked via the base to a detectable label by a desirable linker, which label may be a fluorophore, for example.
- the detectable label may instead, if desirable, be incorporated into the blocking groups of formula "Z" .
- the linker can be acid labile, photolabile or contain. a disulfide linkage.
- Other linkages, in particular phosphine-cleavable azide- containing linkers, may be employed in the invention as described in greater detail. Preferred labels and linkages included those disclosed in WO 03/048387.
- the incorporation of the molecule may be accomplished via a terminal transferase, a polymerase or a reverse transcriptase .
- the molecule is incorporated by a polymerase and particularly from Thermococcus sp . , such as 9°N.
- the polymerase is a mutant 9°N A485L and even more preferably is a double mutant Y409V and A485L.
- the blocking group and the label may be removed in a single chemical treatment step.
- the blocking group is cleaved simultaneously with the label. This will of course be a feature inherent to those blocking groups of formula Z which incorporate a detectable label .
- the blocked and labelled modified nucleotide constructs of the nucleotide bases A, T, C and G are recognised as substrates by the same polymerase enzyme.
- each of the nucleotides can be brought into contact with the target sequentially, with removal of non-incorporated nucleotides prior to addition of the next nucleotide, ' where detection and removal of the label and the blocking group is carried out either after addition of each nucleotide, or after addition of all four nucleotides.
- all of the nucleotides can be brought into contact with the target simultaneously, i.e., a composition comprising all of the different nucleotides is brought into contact with the target, and non-incorporated nucleotides are removed prior to detection and subsequent to removal of the label and the blocking group.
- the methods can comprise a first step and a second step, where in the first step, a first composition comprising two of the four types of modified nucleotides is brought into contact with the target, and non- incorporated nucleotides are removed prior to detection and subsequent to removal of the label and the blocking group, and where in the second step, a second composition comprising the two nucleotides not included in the first composition is brought into contact with the target, and non-incorporated nucleotides are removed prior to detection and subsequent to removal of the label and blocking group, and where the first steps and the second step can be optionally repeated one or more times.
- the methods described herein can also comprise a first step and a second step, where in the first step, a composition comprising one of the four nucleotides is brought into contact with the target, and non- incorporated nucleotides are removed prior to detection and subsequent to removal of the label and blocking group, and where in the second step, a second composition comprising the three nucleotides not included in the first composition is brought into contact with the target, and non- incorporated nucleotides are removed prior to detection and subsequent to removal of the label and blocking group, and where the first steps and the second step can be optionally repeated one or more times.
- the methods described herein can also comprise a first step and a second step, where in the first step, a first composition comprising three of the four nucleotides is brought into contact with the target, and non-incorporated nucleotides are removed prior to detection and subsequent to removal of the label and blocking group and where in the second step, a composition comprising the nucleotide not included in the first composition is brought into contact with the target, and non-incorporated nucleotides are removed prior to detection and subsequent to removal of the label and blocking group, and where the first steps and the second step can be optionally repeated one or more times.
- the incorporating step in the methods of the invention can be accomplished via a terminal transferase, a polymerase or a reverse transcriptase as hereinbefore defined.
- the detectable label and/or the cleavable linker can be of a size sufficient to prevent the incorporation of a second nucleotide or nucleoside into the nucleic acid molecule.
- each of the four nucleotides in certain methods described herein for determining the sequence of a target single-stranded polynucleotide, each of the four nucleotides, one of which will be complementary to the first unpaired base in the target polynucleotide, can be brought into contact with the target sequentially, optionally with removal of non- incorporated nucleotides prior to addition of the next nucleotide. Determination of the success of the incorporation may be carried out either after provision of each nucleotide, or after the addition of all of the nucleotides added.
- nucleotides complementary to the incorporated nucleotide can be brought into contact with the target simultaneously, i.e., a composition comprising all of the different nucleotide (i.e. A, T, C and G or A, U, C and G) is brought into contact with the target, and non-incorporated nucleotides removed prior to detection and removal of the label (s) .
- the methods involving sequential addition of nucleotides may comprise a first substep and optionally one or more subsequent substeps.
- a composition comprising one, two or three of the four possible nucleotides is provided, i.e. brought into contact with, the target . Thereafter any unincorporated nucleotides may be removed and a detecting step may be conducted to determine whether one of the nucleotides has been incorporated. If one has been incorporated, the cleavage of the linker may be effected. In this way the identity of a nucleotide in the target polynucleotide may be determined. The nascent polynucleotide may then be extended to determine the identity of the next unpaired nucleotide in the target oligonucleotide .
- first substep above does not lead to incorporation of a nucleotide, or if this is not known, since the presence of incorporated nucleotides is not sought immediately after the first substep, one or more subsequent substeps may be conducted in which some or all of those nucleotides not provided in the first substep are provided either, as appropriate, simultaneously or subsequently. Thereafter any unincorporated nucleotides may be removed and a detecting step conducted to determine whether one of the classes of nucleotide has been incorporated. If one has been incorporated, cleavage of the linker may be effected. In this way the identity of a nucleotide in the target polynucleotide may be determined.
- the nascent polynucleotide may then be extended to determine the identity of the next unpaired nucleotide in the target oligonucleotide. If necessary, a third and optionally a fourth substep may be effected in a similar manner to the second substep. Obviously, once four substeps have been effected, all four possible nucleotides will have been provided and one will have been incorporated.
- nucleotide It is desirable to determine whether a type or class of nucleotide has been incorporated after any particular combination comprising one, two or three nucleotides has been provided. In this way the unnecessary cost and time expended in providing the other nucleotide (s) is obviated. This is not a required feature of the invention, however. It is also desirable, where the method for sequencing comprises one or more substeps, to remove any unincorporated nucleotides before further nucleotide are provided. Again, this is not a required feature of the invention. Obviously, it is necessary that at least some and preferably as many as practicable of the unincorporated nucleotides are removed prior to the detection of the incorporated nucleotide.
- kits of the invention include: (a) individual nucleotides according to the hereinbefore described invention, where each nucleotide has a base that is linked to a detectable label via a cleavable linker, or a detectable label linked via an optionally cleavable liner to a blocking group of formula Z, and where the detectable label linked to each nucleotide can be distinguished upon detection from the detectable label used for other three nucleotides; and (b) packaging materials therefor.
- the kit can further include an enzyme for incorporating the nucleotide into the complementary nucleotide chain and buffers appropriate for the action of the enzyme in addition to appropriate chemicals for removal of the blocking group and the detectable label, which can preferably be removed by the same chemical treatment step.
- the nucleotides/nucleosides are suitable for use in many different DNA-based methodologies, including DNA synthesis and DNA sequencing protocols.
- Fig. 1 shows exemplary nucleotide structures useful in the invention.
- X can be H, phosphate, diphosphate or triphosphate .
- R x and R 2 can be the same or different, and can be selected from H, OH, or any group which can be transformed into an OH, including, but not limited to, a carbonyl .
- Some suitable functional groups for Ri and R 2 include the structures shown in Fig. 3 and Fig . 4.
- Fig. 2 shows structures of linkers useful in certain aspects of the invention , including (1) disulfide linkers and acid labile linkers, (2) dialkoxybenzyl linkers, (3) Sieber linkers, (4) indole linkers and (5) t-butyl Sieber linkers.
- Fig. 3 shows some functional molecules useful , in the invention, including some cleavable linkers and some suitable hydroxyl protecting groups.
- Rx and R 2 may be the same of different, and can be H, OH, or any group which can be transformed into an OH group, including a carbonyl .
- R 3 represents one or more substituents independently selected from alkyl, alkoxyl , amino or halogen groups .
- R 4 and R 5 can be H or alkyl
- R 6 can be alkyl, cycloalkyl, alkenyl, cycloalkenyl or benzyl.
- X can be H, phosphate, diphosphate or triphosphate.
- Fig. 4 is a schematic illustration of some of the Z blocking groups that can be used according to the invention.
- Fig. 5 shows two cycles of incorporation of labelled and blocked DGTP, DCTP and dATP respectively (compounds
- Fig. 6 shows six cycles of incorporation of labelled and blocked DTTP (compound 6) .
- Fig.7 shows the effective blocking by compound 38 (a
- the present invention relates to nucleotide or nucleoside molecules that are modified by the reversible covalent attachment of a 3 ' -OH blocking groups thereto, and which molecules may be used in reactions where blocked nucleotide or nucleoside molecules are required, such as in sequencing reactions, polynucleotide synthesis and the like.
- the blocking group is an allyl group
- it may be introduced into the 3 '-position using standard literature procedures such as that used by Metzker
- the allyl groups are removed by reacting in aqueous solution a compound of formula R-O-allyl, R 2 N (allyl), RNH(allyl), RN (allyl) 2 or R-S-allyl (wherein R is a water-soluble biological molecule) with a transition metal, wherein said transition metal is capable of forming a metal allyl complex, in the presence of one or more ligands selected from the group comprising water- soluble phosphine and water-soluble mixed nitrogen- phosphine ligands.
- the water-soluble biological molecule is not particularly restricted provided, of course, it contains one or more hydroxyl, acid, amino, amide or thiol functionalities protected with an allyl group. Allyl esters are examples of compounds of formula R-O-allyl. Preferred functionalities are hydroxyl and amino.
- biological molecule is used to embrace any molecules or class of molecule which performs a biological role. Such molecules include for example, polynucleotides such as DNA and RNA, oligonucleotides and single nucleotides. In addition, peptides and peptide mimetics, such as enzymes and hormones etc., are embraced by the invention.
- Compounds which comprise a secondary amide linkage, such as peptides, or a secondary amine, where such compounds are allylated on the nitrogen atom of the secondary amine or amide are examples of compounds of formula R 2 N (allyl) in which both R groups belong to the same biological molecule.
- Particularly preferred compounds are polynucleotides, (including oligonucleotides) and nucleotides and nucleosides, preferably those which contain one base to which is attached a detectable label linked through a cleavable linker. Such compounds are useful in the determination of sequences of oligonucleotides as described herein.
- Transition metals of use in the invention are any which may form metal allyl complexes, for example platinum, palladium, rhodium, ruthenium, osmium and iridium. Palladium is preferred.
- the transition metal e.g. palladium
- a salt e.g. as a halide.
- Mixed salts such as Na 2 PdCl 4 may also be used.
- Other appropriate salts and compounds will be readily determined by the skilled person and are commercially available, e.g. from Aldrich Chemical Company.
- Suitable ligands are any phosphine or mixed nitrogen-phosphine ligands known to those skilled in the art, characterised in that the ligands are derivatised so as to render them water-soluble, e.g. by introducing one or more sulfonate, amine, hydroxyl (preferably a plurality of hydroxyl) or carboxylate residues. Where amine residues are present, formation of amine salts may assist the solublisation of the ligand and thus the metal -allyl complex.
- appropriate ligands are triaryl phosphines, e.g. triphenyl phosphine, derivatised so as to make them water-soluble.
- trialkyl phosphines e.g. tri-C ⁇ - 6 -alkyl phosphines such as triethyl phosphines; such trialkyl phosphines are likewise derivatised so as to make them water-soluble.
- Sulfonate-containing and carboxylate-containing phosphines are particularly preferred; an example of the former 3 , 3 ' , 3 " -phosphinidynetris (benzenesulfonic acid) which is commercially available from Aldrich Chemical Company as the trisodium salt; and a preferred example of the latter is tris (2 -carboxyethyl) phosphine which is available from Aldrich as the hydrochloride salt.
- the derivatised water-soluble phosphines and nitrogen-containing phosphines described herein may be used as their salts (e.g.
- ligands which may be used to include the following:
- the atoms chelated to the transition metal in the water soluble complex may be part of mono- or polydentate ligands.
- polydentate ligands Some such polydentate ligands are shown above. Whilst monodentate ligands are preferred, the invention thus also embraces methods which use water-soluble bi-, tri-, tetra-, penta- and hexadentate water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands
- allyl blocking groups are of particular utility in sequencing polynucleotides wherein the 3 ' -OH is allylated. However, when present, the 2 ' -OH is equally amenable to allylation, and to deprotection according to the method of the invention if necessary. In fact any allylated alcohol may be deprotected according to the method of the invention.
- allylated alcohols are those derived from primary and secondary alcohols. Particularly preferred are allylated nucleosides and nucleotides as described herein. It is possible to deprotect tertiary allylated alcohols - the reaction is simply slower (although deprotection may be in such, and other deprotections of this invention, accelerated if necessary by heating the solution, e.g. to 40 °C, preferably 50 °C or higher such as approximately 60 °C or even up to 80 °C) .
- the aqueous solution in which allyl deprotection is effected need not be 100% (as the continuous phase) .
- substantially pure water e.g. at least 98 vol% preferably about 100 vol%) is preferred.
- Cosolvents are generally not required although they can assist in the solublisation of the allylated substrate for the deallylation.
- biomolecules are readily soluble in water (e.g. pure water) in which the deprotection reaction described herein may be effected.
- one or more water- miscible cosolvents may be employed.
- Appropriate solvents include acetonitrile or dimethylsulfoxide, methanol , ethanol and acetone, methanol being preferred. Less preferred solvents include tetrahydrofuran (THF) and dioxane .
- a soluble metal complex comprising a transition metal and one or more water-soluble phosphine and water-soluble nitrogen-containing phosphine ligands. More than one type of water-soluble phosphine/nitrogen- containing phosphine ligand may be used in a deallylation reaction although generally only one type of these classes of ligand will be used in a given reaction. We believe the deallylation reaction to be catalytic. Accordingly, the quantity of transition metal, e.g. palladium, may be less than 1 mol% (calculated relative to the allyl -protected compound to be deprotected) .
- the amount of catalyst may be much less than 1 mol%, e.g. ⁇ 0.50 mol%, preferably ⁇ 0.10 mol%, particularly ⁇ 0.05mol%. Even lower quantities of metal may be used, for example ⁇ 0.03 or even ⁇ 0.01 mol%. As those skilled in the art will be aware, however, as quantity of catalyst is reduced, so too is the speed of the reaction. The skilled person will be able to judge, in any instance, the precise quantity of transition metal and thus catalyst most optimally suited to any particular deallylation reaction.
- the quantity of water- soluble phosphorus-containing ligand (s) used must be greater than 1 molar equivalent (again calculated relative to the allyl-protected compound to be deprotected) .
- Even higher quantities of ligand e.g. >20 mole equivalents may be used if desired.
- the skilled person will be able to determine the quantity of ligand best suited to any individual reaction.
- each R' may be independently H or an alkyl
- Z is of formula -C (R' ) 2 -0-R" , - C(R' ) 2 -N(R") 2 , -C(R' ) 2 -N(H)R" and -C(R') 2 -SR".
- Z is of the formula -C(R') 2 - O-R", -C(R' ) 2 -N(R") 2 , and -C(R') 2 -SR".
- R" may be a benzyl group or a substituted benzyl group.
- groups of structure -O-Z wherein Z is -C(R' ) 2 -N(R" ) 2 are those in which -N(R") 2 is azido (-N 3 ) .
- One preferred such example is azidomethyl wherein each R' is H.
- R' in Z groups of formula -C(R') 2 -N 3 and other Z groups may be any of the other groups discussed herein.
- R' groups include C ⁇ - 6 alkyl, particularly methyl and ethyl, and the following (in which each structure shows the bond which connects the R' moiety to the carbon atom to which it is attached in the Z groups; the asterisks (*) indicate the points of attachment) :
- each R is an optionally substituted C ⁇ - ⁇ 0 alkyl group, an optionally substituted alkoxy group, a halogen atom or functional group such as hydroxyl, amino, cyano, nitro, carboxyl and the like
- Het is a heterocyclic (which may for example be a heteroaryl group) .
- R' groups shown above are preferred where the other R' group is the same as the first or is hydrogen.
- the azido group may be converted to amino by contacting such molecules with the phosphine or nitrogen-containing phosphines ligands described in detail in connection with the transition metal complexes which serve to cleave the allyl groups from compounds of formula PN-O-allyl, formula R-O-allyl, R 2 N (allyl), RNH(allyl), RN (allyl) 2 and R-S-allyl.
- the transition metal complexes which serve to cleave the allyl groups from compounds of formula PN-O-allyl, formula R-O-allyl, R 2 N (allyl), RNH(allyl), RN (allyl) 2 and R-S-allyl.
- the azido group in Z groups of formula C(R') 2 N3 may be converted to amino by contacting such molecules with the thiols, in particular water-soluble thiols such as dithiothreitol (DTT) .
- DTT dithiothreitol
- R' group represents a detectable label attached through a linking group
- the other R' group or any other part of "Z" will generally not contain a detectable label, nor will the base of the nucleoside or nucleotide contain a detectable label.
- Appropriate linking groups for connecting the detectable label to the 3' blocking group will be known to the skilled person and examples of such groups are described in greater detail hereinafter.
- linkages in R' groups containing detectable labels are those which contain one or more amide bonds.
- Such linkers may also contain an arylene, e.g. phenylene, group in the chain (i.e. a linking moiety -Ar- where the phenyl ring is part of • the linker by way of its 1,4-disposed carbon atoms) .
- the phenyl ring may be substituted at its non-bonded position with one or more substituents such as alkyl, hydroxyl, alkyloxy, halide, nitro, carboxyl or cyano and the like, particularly electron-withdrawing groups, which electron-withdrawing is either by induction or resonance.
- the linkage in the R' group may also include moieties such a -0-, -S(0) q , wherein q is 0, 1 or 2 or NH or Nalkyl . Examples of such Z groups are as follows:
- EWG electron-withdrawing group
- n is an integer of from 1 to 50, preferably 2-20, e.g. 3 to 10; and fluor indicates a fluorophore
- An example of an electron-withdrawing group by resonance is nitro; a group which acts through induction is fluoro.
- fluorophore is indicated as being the detectable label present, other detectable groups as discussed in greater detail hereinafter may be included instead.
- each R" is or is part of a removable protecting group.
- R" may be a benzyl group or is substituted benzyl group is an alternative embodiment.
- R is a benzyl group
- the phenyl ring may bear a linker group to which is attached a fluorophore or other detectable group. Introduction of such groups does not prevent the ability to remove such R"s and they do not prevent the generation of the desired unstable intermediates during deprotection of blocking groups of formula Z.
- a "nucleotide” consists of a nitrogenous base, a sugar, and one or more phosphate groups. They are monomeric units of a nucleic acid sequence.
- the sugar is a ribose, and in DNA a deoxyribose, i.e. a sugar lacking a hydroxyl group that is present in ribose.
- the nitrogenous base is a derivative of purine or pyrimidine .
- the purines are adenine (A) and guanine (G)
- the pyrimidines are cytosine (C) and thymine (T) (or in the context of RNA, uracil (U) ) .
- a nucleotide is also a phosphate ester or a nucleoside, with esterification occurring on the hydroxyl group attached to C-5 of the sugar. Nucleotides are usually mono, di- or triphosphates .
- a "nucleoside" is structurally similar to a nucleotide, but is missing the phosphate moieties.
- An example of a nucleoside analogue would be one in which the label is linked to the base and there is no phosphate group attached to the sugar molecule.
- the base is usually referred to as a purine or pyrimidine, the skilled person will appreciate that derivatives and analogues are available which do not alter the capability of the nucleotide or nucleoside to undergo Watson-Crick base pairing.
- “Derivative” or “analogue” means a compound or molecule whose core structure is the same as, or closely resembles that of, a parent compound, but which has a chemical or physical modification, such as a different or additional side group, or 2' and or 3' blocking groups, which allows the derivative nucleotide or nucleoside to be linked to another molecule.
- the base can be a deazapurine.
- the derivatives should be capable of undergoing Watson-Crick pairing.
- “Derivative” and “analogue” also mean a synthetic nucleotide or nucleoside derivative having modified base moieties and/or modified sugar moieties. Such derivatives and analogs are discussed in, e.g., Scheit, Nucleotide Analogs (John Wiley & Son, 1980) and Uhlman et al . , Chemical Reviews 90:543-584, 1990. Nucleotide analogs can also comprise modified phosphodiester linkages, including phosphorothioate, phosphorodithioate, alkyl- phosphonate, phosphoranilidate and phosphoramidate linkages. The analogs should be capable of undergoing Watson-Crick base pairing. "Derivative”, “analog” and “modified” as used herein, may be used interchangeably, and are encompassed by the terms “nucleotide” and “nucleoside” defined herein.
- incorporating means becoming part of a nucleic acid (eg DNA) molecule or oligonucleotide or primer.
- An oligonucleotide refers to a synthetic or natural molecule comprising a covalently linked sequence of nucleotides which are formed by a phosphodiester or modified phosphodiester bond between the 3 ' position of the pentose on one nucleotide and the 5 ' position of the pentose on an adjacent nucleotide.
- alkyl covers straight chain, branched chain and cycloalkyl groups.
- alkyl refers to groups having 1 to 10 carbon atoms, for example 1 to 8 carbon atoms, and typically from 1 to 6 carbon atoms, for example from 1 to 4 carbon atoms .
- alkyl groups include methyl, ethyl, propyl , isopropyl, n- butyl, isobutyl, tert-butyl, n-pentyl, 2-pentyl, 3- pentyl, 2 -methyl butyl, 3 -methyl butyl, and n-hexyl and its isomers.
- cycloalkyl groups are those having from 3 to 10 ring atoms, particular examples including those derived from cyclopropane, cyclobutane, cyclopentane, cyclohexane and cycloheptane, bicycloheptane and decalin.
- alkyl (including cycloalkyl) groups are substituted, particularly where these form either both of the R' groups of the molecules of the invention
- substituents include halogen substituents or functional groups such as hydroxyl, amino, cyano, nitro, carboxyl and the like. Such groups may also be substituents, where appropriate, of the other R' groups in the molecules of the invention.
- the term amino refers to groups of type NR * R ** , wherein R * and R ** are independently selected from hydrogen, a C - 6 alkyl group (also referred to as C!- 6 alkylamino or di-C ⁇ - 6 alkylamino) .
- halogen as used herein includes fluorine, chlorine, bromine and iodine.
- nucleotide molecules of the present invention are suitable for use in many different methods where the detection of nucleotides is required.
- DNA sequencing methods such as those outlined in U.S. Pat. No. 5,302,509 can be carried out using the nucleotides .
- the present invention can make use of conventional detectable labels. Detection can be carried out by any suitable method, including fluorescence spectroscopy or by other optical means .
- the preferred label is a fluorophore, which, after absorption of energy, emits radiation at a defined wavelength.
- Many suitable fluorescent labels are known. For example, Welch et al . (Chem. Eur. J. 5 (3) :951-960, 1999) discloses dansyl-functionalised fluorescent moieties that can be used in the present invention. Zhu et al . ( Cyto etry 28:206-211, 1997) describes the use of the fluorescent labels Cy3 and Cy5, which can also be used in the present invention. Labels suitable for use are also disclosed in Prober et al .
- fluorescent labels include, but are not limited to, fluorescein, rhodamine (including TMR, texas red and Rox) , alexa, bodipy, acridine, coumarin, pyrene, benzanthracene and the cyanins .
- bi-fluorophore FRET cassettes (Tet. Let. 46:8867-8871, 2000) are well known in the art and can be utilised in the present invention.
- Multi-fluor dendrimeric systems (J. Amer. Chem. Soc . 123:8101-8108, 2001) can also be used.
- fluorescent labels are preferred, other forms of detectable labels will be apparent as useful to those of ordinary skill.
- microparticles including quantum dots (Empodocles et al . , Nature 399:126-130, 1999), gold nanoparticles (Reichert et al . , Anal . Chem . 72:6025-6029, 2000) and microbeads (Lacoste et al . , Proc . Natl . Acad . Sci USA 97(17) :9461-9466, 2000) can all be used.
- Multi-component labels can also be used in the invention.
- a multi-component label is one which is dependent on the interaction with a further compound for detection.
- Biotin-streptavidin The most common multi-component label used in biology is the biotin-streptavidin system. Biotin is used as the label attached to the nucleotide base. Streptavidin is then added separately to enable detection to occur. Other multi-component systems are available. For example, dinitrophenol has a commercially available fluorescent antibody that can be used for detection.
- nucleotides The invention has been and will be further described with reference to nucleotides. However, unless indicated otherwise, the reference to nucleotides is also intended to be applicable to nucleosides. The invention will also be further described with reference to DNA, although the description will also be applicable to RNA, PNA, and other nucleic acids, unless otherwise indicated.
- the modified nucleotides of the invention may use a cleavable linker to attach the label to the nucleotide.
- a cleavable linker ensures that the label can, if required, be removed after detection, avoiding any interfering signal with any labelled nucleotide incorporated subsequently.
- cleavable linkers is preferable, particularly in the methods of the invention hereinbefore described except where the detectable label is attached to the nucleotide by forming part of the "Z" group.
- Sanger sequencing methods and related protocols (Sanger-type) , which rely upon randomised chain-termination at a particular type of nucleotide.
- An example of a Sanger-type sequencing protocol is the BASS method described by Metzker (infra) .
- Other Sanger-type sequencing methods will be known to those skilled in the art.
- Sanger and Sanger-type methods generally operate by the conducting of an experiment in which ⁇ eight types of nucleotides are provided, four of which contain a 3'OH group; and four of which omit the OH group and which are labeled differently from each other.
- the nucleotides used which omit the 3 ' OH group - dideoxy nucleotides - are conventially abbreviated to ddNTPs.
- ddNTPs are conventially abbreviated to ddNTPs.
- the sequence of the target oligonucleotide may be determined.
- nucleotides of the present invention may be of utility in Sanger methods and related protocols since the same effect achieved by using ddNTPs may be achieved by using the novel 3 ' -OH blocking groups described herein: both prevent incorporation of subsequent nucleotides.
- the invention provides the use of such nucleotides in a Sanger or a Sanger-type sequencing method.
- monitoring of the incorporation of 3 ' OH blocked nucleotides may be determined by use of radioactive 32 P in the phosphate groups attached. These may be present -in either the ddNTPs themselves or in the primers used for extension. Where the blocking groups are of formula "Z" , this represents a further aspect of the invention.
- the invention provides the use of a nucleotide having a 3 OH group blocked with a "Z" group in a Sanger or a Sanger-type sequencing method.
- a 32 P detectable label may be present in either the ddNTPs used in the primer used for extension.
- Cleavable linkers are known in the art, and conventional chemistry can be applied to attach a linker to a nucleotide base and a label.
- the linker can be cleaved by any suitable method, including exposure to acids, bases, nucleophiles, electrophiles, radicals, metals, reducing or oxidising agents, light, temperature, enzymes etc.
- the linker as discussed herein may also be cleaved with the same catalyst used to cleave the 3'0-blocking group bond.
- Suitable linkers can be adapted from standard chemical blocking groups, as disclosed in Greene & Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons. Further suitable cleavable linkers used in solid-phase synthesis are disclosed in Guillier et al . (Chem. Rev. 100:2092-2157, 2000) .
- nucleoside cleavage site can be located at a position on the linker that ensures that part of the linker remains attached to the nucleotide base after cleavage .
- the linker can be attached at any position on the nucleotide base provided that Watson-Crick base pairing can still be carried out.
- the linker is attached via the 7-position of the purine or the preferred deazapurine analogue, via an 8 -modified purine, via an N-6 modified adenosine or an N-2 modified guanine.
- attachment is preferably via the 5-position on cytosine, thymidine or uracil and the N-4 position on cytosine.
- Suitable nucleotide structures are shown in Fig. 1. For each structure in Fig.
- Ri and R 2 can be the same or different, and are selected from H, OH, O-allyl, or formula Z as described herein or any other group which can be transformed into an OH, including, but not limited to, a carbonyl , provided that at least one of Ri and R 2 is O-allyl or formula Z as described herein.
- Some suitable functional groups for R x and R 2 include the structures shown in Figs. 3 and 4.
- Suitable linkers include, but are not limited to, disulfide linkers (1) , acid labile linkers (2, 3, 4 and 5; including dialkoxybenzyl linkers (e.g., 2), Sieber linkers (e.g., 3), indole linkers (e.g., 4), t-butyl Sieber linkers (e.g., 5)), electrophilically cleavable linkers, nucleophilically cleavable linkers, photocleavable linkers , , cleavage under reductive conditions, oxidative conditions, cleavage via use of safety-catch linkers, and cleavage by elimination mechanisms .
- A. Electrophilically cleaved linkers include, but are not limited to, disulfide linkers (1) , acid labile linkers (2, 3, 4 and 5; including dialkoxybenzyl linkers (e.g., 2), Sieber linkers (e.g., 3), indole linkers (e.g.,
- Electrophilically cleaved linkers are typically cleaved by protons and include cleavages sensitive to acids.
- Suitable linkers include the modified benzylic systems such as trityl, p-alkoxybenzyl esters and p- alkoxybenzyl amides.
- Other suitable linkers include tert-butyloxycarbonyl (Boc) groups and the acetal system.
- thiophilic metals such as nickel, silver or mercury
- thioacetal or other sulfur-containing protecting groups can also be considered for the preparation of suitable linker molecules .
- Nucleophilic cleavage is also a well recognised method in the preparation of linker molecules.
- Groups such as esters that are labile in water (i.e., can be cleaved simply at basic pH) and groups that are labile to non-aqueous nucleophiles, can be used.
- Fluoride ions can be used to cleave silicon-oxygen bonds in groups such as triisopropyl silane (TIPS) or t-butyldimethyl silane (TBDMS) .
- Photocleavable linkers have been used widely in carbohydrate chemistry. It is preferable that the light required to activate cleavage does not affect the other components of the modified nucleotides. For example, if a fluorophore is used as the label, it is preferable if this absorbs light of a different wavelength to that required to cleave the linker molecule.
- Suitable linkers include those based on 0- nitrobenzyl compounds and nitroveratryl compounds. Linkers based on benzoin chemistry can also be used (Lee et al . , J. Org. Chem. 64:3454-3460, 1999).
- linkers There are many linkers known that are susceptible to reductive cleavage. Catalytic hydrogenation using palladium-based catalysts has been used to cleave benzyl and benzyloxycarbonyl groups. Disulfide bond reduction is also known in the art.
- Oxidation-based approaches are well known in the art. These include oxidation of p-alkoxybenzyl groups and the oxidation of sulfur and selenium linkers.
- aqueous iodine to cleave disulfides and other sulfur or selenium-based linkers is also within the scope of the invention.
- Safety-catch linkers are those that cleave in two steps.
- the first step is the generation of a reactive nucleophilic center followed by a second step involving an intra-molecular cyclization that results in cleavage.
- levulinic ester linkages can be treated with hydrazine or photochemistry to release an active amine, which can then be cyclised to cleave an ester elsewhere in the molecule (Burgess et al . , J. Org. Chem. 62:5165- 5168, 1997) .
- Elimination reactions can also be used.
- the base-catalysed elimination of groups such as Fmoc and cyanoethyl can be used.
- groups such as Fmoc and cyanoethyl
- palladium-catalysed reductive elimination of allylic systems can be used.
- the linker can comprise a spacer unit.
- the spacer distances e.g., the nucleotide base from the cleavage site or label.
- the length of the linker is unimportant provided that the label is held a sufficient distance from the nucleotide so as not to interfere with any interaction between the nucleotide and an enzyme.
- the linker may consist of the same functionality as the block. This will make the deprotection and deblocking process more efficient, as only a single treatment will be required to remove both the label and the block.
- linkers are phosphine- cleavable azide containing linkers.
- a method for determining the sequence of a target polynucleotide can be carried out by contacting the target polynucleotide separately with the different nucleotides to form the complement to that of the target polynucleotide, and detecting the incorporation of the nucleotides.
- Such a method makes use of polymerisation, whereby a polymerase enzyme extends the complementary strand by incorporating the correct nucleotide complementary to that on the target.
- the polymerisation reaction also requires a specific primer to initiate polymerisation. For each cycle, the incorporation of the modified nucleotide is carried out by the polymerase enzyme, and the incorporation event is then determined.
- polymerase enzymes include DNA polymerase I, the Klenow fragment, DNA polymerase III, T4 or T7 DNA polymerase, Taq polymerase or Vent polymerase.
- Polymerases engineered to have specific properties can also be used.
- the molecule is preferably incorporated by a polymerase and particularly from Thermococcus sp. , such as 9°N. Even more preferably, the polymerase is a mutant 9°N A485L and even more preferably is a double mutant Y409V and A485L.
- An example of one such preferred enzyme is Thermococcus sp.
- the sequencing methods are preferably carried out with the target polynucleotide arrayed on a solid support.
- Multiple target polynucleotides can be immobilised on the solid support through linker molecules, or can be attached to particles, e.g., microspheres, which can also be attached to a solid support material.
- the polynucleotides can be attached to the solid support by a number of means, including the use of biotin-avidin interactions.
- Methods for immobilizing polynucleotides on a solid support are well known in the art, and include lithographic techniques and "spotting" individual polynucleotides in defined positions on a solid support. Suitable solid supports are known in the art, and include glass slides and beads, ceramic and silicon surfaces and plastic materials.
- the support is usually a flat surface although microscopic beads (microspheres) can also be used and can in turn be attached to another solid support by known means.
- the microspheres can be of any suitable size, typically in the range of from 10 nm to 100 nm in diameter.
- the polynucleotides are attached directly onto a planar surface, preferably a planar glass surface. Attachment will preferably be by means of a covalent linkage.
- the arrays that are used are single molecule arrays that comprise polynucleotides in distinct optically resolvable areas, e.g., as disclosed in International Application No. WO00/06770.
- the sequencing method can be carried out on both single polynucleotide molecule and multi- polynucleotide molecule arrays, i.e., arrays of distinct individual polynucleotide molecules and arrays of distinct regions comprising multiple copies of one individual polynucleotide molecule.
- Single molecule arrays allow each individual polynucleotide to be resolved separately. The use of single molecule arrays is preferred. Sequencing single molecule arrays non-destructively allows a spatially addressable array to be formed.
- the method makes use of the polymerisation reaction to generate the complementary sequence of the target.
- Conditions compatible with polymerization reactions will be apparent to the skilled person.
- To carry out the polymerase reaction it will usually be necessary to first anneal a primer sequence to the target polynucleotide, the primer sequence being recognised by the polymerase enzyme and acting as an initiation site for the subsequent extension of the complementary strand.
- the primer sequence may be added as a separate component with respect to the target polynucleotide.
- the primer and the target polynucleotide may each be part of one single stranded molecule, with the primer portion forming an intramolecular duplex with a part of the target, i.e., a hairpin loop structure. This structure may be immobilised to the solid support at any point on the molecule.
- Other conditions necessary for carrying out the polymerase reaction including temperature, pH, buffer compositions etc., will be apparent to those skilled in the art. '
- the modified nucleotides of the invention are then brought into contact with the target polynucleotide, to allow polymerisation to occur.
- the nucleotides may be added sequentially, i.e., separate addition of each nucleotide type (A, T, G or C) , or added together. If they are added together, it is preferable for each nucleotide type to be labelled with a different label. This polymerisation step is allowed to proceed for a time sufficient to allow incorporation of a nucleotide .
- Nucleotides that are not incorporated are then removed, for example, by subjecting the array to a washing step, and detection of the incorporated labels may then be carried out .
- Detection may be by conventional means, for example if the label is a fluorescent moiety, detection of an incorporated base may be carried out by using a confocal scanning microscope to scan the surface of the array with a laser, to image a fluorophore bound directly to the incorporated base. " Alternatively, a sensitive 2-D detector, such as a charge-coupled detector (CCD) , can be used to visualise the individual signals generated. However, other techniques such as scanning near- field optical microscopy (SNOM) are available and may be used when imaging dense arrays. For example, using SNOM, individual polynucleotides may be distinguished when separated by a distance of less than 100 nm, e.g., 10 nm to 10 ⁇ m.
- CCD charge-coupled detector
- the label may be removed using suitable conditions that cleave the linker and the 3' OH block to allow for incorporation of further modified nucleotides of the invention.
- Appropriate conditions may be those described herein for allyl group and for "Z" group deprotections. These conditions can serve to deprotect both the linker (if cleavable) and the blocking group.
- the linker may be deprotected separately from the allyl group by employing methods of cleaving the linker known in the art (which do not sever the 0-blocking group bond) followed by deprotection.
- Nucleotides bearing this blocking group at the 3 'position have been synthesised, shown to be successfully incorporated by DNA polymerases, block efficiently and may be subsequently removed under neutral, aqueous conditions using water soluble phosphines or thiols allowing further extension:
- Tetrasodium diphosphate decahydrate (1.5 g, 3.4 mmol) was dissolved in water (34 ml) and the solution was applied to a column of dowex in the H + form. The column was eluted with water. The eluent dropped directly into a cooled (ice bath) and stirred solution of tri-n-butylamine (1.6 ml, 6.8 mmol) in EtOH (14 ml) . The column was washed until the pH of the eluent increased to 6. The aq. ethanol solution was evaporated to dryness and then co-evaporated twice with ethanol and twice with anhydrous DMF. The residue was dissolved in DMF (6.7 ml) .
- the nucleoside (4) and proton sponge was dried over
- the starting disulfide (4.0 mg, 13.1 ⁇ mol) was dissolved in DMF (300 ⁇ L) and diisopropylethylamine (4 ⁇ L) was slowly added. The mixture was stirred at room temperature and a solution of Cy-3 dye (5 mg, 6.53 ⁇ mol) in DMF (300 ⁇ L) was added over 10 min.
- the starting material (8) (lOg, 20.43 mmol) was azeotroped in dry pyridine (2 x 100 ml) then dissolved in dry pyridine (160 ml) under ⁇ 2 atmosphere. Chlorotrimethylsilane (10 ml, 79.07 mmol) added drop wise to the solution and stirred for 2 hours at room temperature. Benzoyl chloride (2.6 ml, 22.40 mmol) was then added to solution and stirred for one further hour. The reaction mixture was cooled to 0°C, distilled water (50 ml) added slowly to the solution and stirred for 30 minutes.
- the starting material (14) (1.65 g, 2.99 mmol was dissolved in DCM (18 ml) and cooled to 0°C. Cyclohexene (1.5 ml, 14.95 mmol) and S0 2 C1 2 (0.72 ml, 8.97 mmol) were added and stirred 1 h in ice bath. TLC indicated starting material still to be present whereupon a further aliquot of S0 2 C1 2 (0.24 ml) was added and the mixture stirred for 1 h at 0°C. Volatiles were removed by evaporation to yield a light brown solid that was redissolved in 18 ml of dry DMF (18 ml) under N 2 .
- the starting material (140 mg, 0.22 mmol) was dissolved in THF (7.5 ml).
- TBAF IM soln. in THF, 0.25 ml
- Volatile material removed under reduced pressure to yield a brown gel that was purified by flash chromatography (EtOAc:DCM 7:3) to yield the desired product (16) as a light coloured crystalline solid (0.9 g, 76%).
- the expected triphosphate was eluted from the column at approx. 0.60 M TEAB.
- a second purification was done by HPLC in a Zorbax SB-C18 column (21.2 mm i.d. x 25 cm) eluted with 0.1M TEAB (pump A) and 30% CH 3 CN in 0.1M TEAB (pump B) using a gradient as follows: 0-5 min 5% B, ⁇ .2 ml; 5-25 min 80% B, ⁇ .8 ml; 25-27 min 95 %B, ⁇ .8 ml; 27-30 min 95 %B, ⁇ .8 ml; 30-32 min 5 %B, ⁇ .8 ml; 32-35 min 95 %B, ⁇ .2 ml, affording the product described above with a r t (17) : 20.8 (14.5 ⁇ mols, 2.5% yield); 31 P NMR (D 2 0, 162 MHz) ⁇ -5.59 (d, J "
- Alexa Fluor 488-NHS 35 mg, 54 ⁇ mol was dissolved in DMF (700 ⁇ L) and, to ensure full activation, 4-DMAP (7 mg, 59 ⁇ mol) and N, N ' - disuccinimidyl carbonate (15 mg, 59 ⁇ mol) were sequentially added. After 15 min on complete activation, a solution of the starting disulfide (32.0 mg, 108 ⁇ mol) in DMF (300 ⁇ L) containing diisopropylethylamine (4 ⁇ L) was added over the solution of the activated dye.
- Alexa Fluor 488 disulfide linker (3.4 ⁇ mol, 2.37mg) in DMF (200 ⁇ L) was added 4-DMAP (0.75 mg, 5.1 ⁇ mol) and N, N-disuccinimidyl carbonate (1.70 mg, 5.1 ⁇ mol) .
- the mixture was stirred for 15 to full activation of the acid, then it was added into the solution of the nucleotide (17) (3.45 mg, 6.0 ⁇ mol) in DMF (0.3 ml) containing ⁇ Bu 3 N (40 ⁇ L) at 0 °C .
- the mixture was sonicated for 3 min and then continuously stirred for 16 h in the absence of light.
- Tetrasodium diphosphate decahydrate (1.5 g, 3.4 mmol) was dissolved in water (34 ml) and the solution was applied to a column of dowex 50 in the H + form. The column was washed with water. The eluent dropped directly into a cooled (ice bath) and stirred solution of tri-n-butyl amine (1.6 ml, 6.8 mmol) in EtOH (14 ml) . The column was washed until the pH of the eluent increased to 6. The aqueous ethanol solution was evaporated to dryness and then co-evaporated twice with ethanol and twice with anhydrous DMF. The residue was dissolved in DMF (6.7 ml) .
- the pale yellow solution was stored over 4A molecular sieves.
- the nucleoside (22) and proton sponge was dried over P 2 0 5 under vacuum overnight.
- a solution of (22) (104 mg, 0.22 mmol) and proton sponge (71 mg, 0.33 mmol) in trimethylphosphate (0.4 ml) was stirred with 4A molecular sieves for 1 h.
- Freshly distilled P0C1 3 (25 ⁇ l, 0.26 mmol) was added and the solution was stirred at 4°C for 2h.
- the mixture was slowly warmed up to room temperature and bis (tri-n-butyl ammonium) pyrophosphate (1.76 ml, 0.88 mmol) and anhydrous tri- n-butyl amine (0.42 ml, 1.76 mmol) were added. After 5 min, the reaction was quenched with 0.1 M TEAB (triethylammonium bicarbonate) buffer (15 ml) and stirred for 3 h. The water was removed under reduced pressure and the resulting residue dissolved in concentrated ammonia (p 0.88, 10 ml) and stirred at room temperature for 16 h. The reaction mixture was then evaporated to dryness.
- TEAB triethylammonium bicarbonate
- the reaction was quenched with TEAB buffer (0.1M, 10 ml) and loaded on a DEAE Sephadex column (2 x 5 cm) .
- the column was first eluted with 0.1 M TEAB buffer (100 ml) and then 1 M TEAB buffer (100 ml) .
- the desired triphosphate product was eluted out with 1 M TEAB buffer.
- t r (24) 23.8 min (Zorbax C18 preparative column, gradient: 5% to 55% B in 30 min, buffer A 0.1M TEAB, buffer B MeCN) .
- the nucleoside (25) (1.13 g, 2.82 mmol) was coevaporated twice in dry pyridine (2 x 10ml) and dissolved in dry pyridine (18 ml) .
- t-butyldiphenylsilylchloride (748 ⁇ l, 2.87 mmol) in small portions at 0°C.
- the reaction mixture was let to warm up at room temperature and left stirring overnight. The reaction was quenched with sat. aq. NaCl solution.
- EtOAc 25 ml was added to reaction mixture and the aqueous layer was extracted with EtOAc three times. After drying the combined organic extracts (MgS0 4 ) the solvent was removed under vacuum. Purification by chromatography. on silica (DCM then EtOAc to EtOAc : MeOH 85:15) gave
- nucleoside (30) and proton sponge was dried over P 2 0 5 under vacuum overnight.
- a solution of (30) (150 mg, 0.294 mmol) and proton sponge (126 mg, 0.588 mmol) in trimethylphosphate (980 ⁇ l) was stirred with 4A molecular sieves for 1 h.
- Freshly distilled POCI- 3 (36 ⁇ l, 0.388 mmol) was added and the solution was stirred at 4°C for 2h.
- the mixture was slowly warmed up to room temperature and bis (tri-n-butyl ammonium) pyrophosphate 0.5 M solution in DMF (2.35 ml, 1.17 mmol) and anhydrous tri-n-butyl amine (560 ⁇ l, 2.35 mmol) was added. After 5 min, the reaction was quenched with 0.1 M TEAB (triethylammonium bicarbonate) buffer (15 ml) and stirred for 3h. The water was removed unde-r reduced pressure and the resulting residue dissolved in concentrated ammonia (p 0.88, 15 ml) and stirred at room temperature for 16 h. The reaction mixture was then evaporated to dryness.
- TEAB triethylammonium bicarbonate
- Tris-HCl pH 8.8 50 mM, Tween-20 0.01%, and MgS0 4 4 mM add 2 ⁇ M compound 6 and 100 nM polymerase ( Thermococcus sp . 9°N exo " Y409V A485L supplied by New England Biolabs) .
- the template consists of a run of 10 adenine bases to show the effect of the block. The reaction is heated to 65 C for 10 mins . To show complete blocking, a chase is performed with the four native, unblocked nucleoside triphosphates . Quantitative incorporation of a single azidomethyl blocked dTTP can be observed and thus the azidomethyl group can be seen to act as an effective block to further incorporation.
- TE buffer Tris-HCl pH 8 , 10 mM and EDTA, 1 mM
- B & W buffer 10 mM Tris-HCl pH 7.5 , 1 mM EDTA and 2.0 M NaCl
- biotinylated 32 P labelled hairpin DNA with appropriate overhanging template sequence. Allow to stand at room temperature for 15 minutes. Remove buffer and wash beads 3 times TE buffer.
- Tris- (2 -carboxyethyl) phosphines trisodium salt (TCEP) (O.IM) is added to the beads and mixed thoroughly. The mixture was then incubated at 65°C for 15 minutes. The deblocking solution is removed and the beads washed 3 times with TE buffer.
- Iodoacetamide (431 mM) in 0.1 mM phosphate pH 6.5 is added to the beads and mixed thoroughly, this is then left at room temperature for 5 minutes. The capping solution is removed and the beads washed 3 times with TE buffer.
- the reaction products can be analysed by placing the bead solution in the well of a standard 12% polyacrylamide DNA sequencing gel in 40% formamide loading buffer. Running the gel under denaturing conditions causes the DNA to be released from the beads and onto the gel.
- the DNA band shifts are affected by both the presence of dye and the addition of extra nucleotides and thus the cleavage of the dye (and block) with the phosphine cause a mobility shift on the gel .
- I efficiently and may be subsequently removed under neutral, aqueous conditions using water soluble phosphines or thiols allowing further extension.
- nucleoside (42) (170 mg, 0.41 mmol) and proton sponge (105 mg, 0.50 mmol) (both previously dried under P 2 0 5 for at least 24 h) in
- the nucleoside (47) and proton sponge was dried over P0 5 under vacuum overnight.
- a solution of (47) (73 mg, 0.16 mmol) and proton sponge (69 mg, 0.32 mmol) trimethylphosphate (0.5 ml) was stirred with 4A molecular sieves for 1 h.
- Freshly distilled P0C1 3 (18 ⁇ l, 0.19 mmol) was added and the solution was stirred at 4°C for 2h.
- the mixture was slowly warmed up to room temperature and bis (tri-n-butyl ammonium) pyrophosphate (1.3 ml, 0.88 mmol) and anhydrous tri-n- butyl amine (0.3 ml, 1.28 mmol) was added.
- reaction was quenched with 0.1 M TEAB (triethylammonium bicarbonate) buffer (10 ml) and stirred for 3h.
- TEAB triethylammonium bicarbonate
- the water was removed under reduced pressure and the resulting residue dissolved in concentrated ammonia (p 0.88, 10 ml) and stirred at room temperature for 16 h.
- the reaction mixture was then evaporated to dryness.
- the residue was dissolved in water and the solution applied to a DEAE-Sephadex A-25 column.
- MPLC was performed with a linear gradient of 2 L each of 0.05 M and 1 M TEAB.
- the triphosphate was eluted between 0.7 M and 0.8 M buffer. Fractions containing the product were combined and evaporated to dryness.
- TBDPSC1 (0.87 g, 2.78 mmol) was added to a stirred solution of 7-deaza-7-iodo-2 ' -deoxyadenosine (1.05 g, 2.78 mmol) in dry pyridine (19 ml) at 5°C under N 2 . After 10 min the solution was allowed to rise to room temperature and stirred for 18h. The solution was evaporated under reduced pressure and the residue purified by flash chromatography on silica (DCM to DCM:MeOH 19:1). This gave the desired product (49) (1.6 g, 83%).
- the nucleoside (54) and proton sponge was dried over P 2 0 5 under vacuum overnight.
- a solution of (54) (84 mg, 0.191 mmol) and proton sponge (49 mg, 0.382 mmol) in trimethylphosphate (600 ⁇ l) was stirred with 4A molecular sieves for 1 h.
- Freshly distilled POCl 3 (36 ⁇ l, 0.388 mmol) was added and the solution was stirred at 4°C for 2h.
- the mixture was slowly warmed up to room temperature and bis (tri-n-butyl ammonium) pyrophosphate 0.5 M in solution in DMF (1.52 ml, 0.764 mmol) and anhydrous tri-n-butyl amine (364 ⁇ l, 1.52 mmol) was added. After 5 min, the reaction was quenched with 0.1 M TEAB (triethylammonium bicarbonate) buffer (5 ml) and stirred for 3h. The water was removed under reduced pressure and the resulting residue dissolved in concentrated ammonia (p 0.88, 5 ml) and stirred at room temperature for 16 h. The reaction mixture was then evaporated to dryness.
- TEAB triethylammonium bicarbonate
- Nucleotides bearing this blocking group have similar properties to the allyl example, though incorporate less rapidly. Deblocking can be achieved efficiently by the use of aqueous buffered cerium ammonium nitrate or DDQ, both conditions initially liberating the hemiacetal (1) which decomposes to the required (2) prior to further extension:
- the 3 ' -OH may also be protected with benzyl groups where the phenyl group is unsubstituted, e.g. with benzyloxymethyl , as well as benzyl groups where the phenyl group bears electron-donating substituents; an example of such an electron-rich benzylic protecting group is 3 , 4-dimethoxybenzyloxymethyl .
- electron-poor benzylic protecting groups such as those in which the phenyl ring is substituted with one or more nitro groups, are less preferred since the conditions required to form the intermediate groups of formulae -C(R') 2 -OH, -C(R') 2 - NH 2 , and -C(R') 2 -SH are sufficiently harsh that the integrity of the polynucleotide can be affected by the conditions needed to deprotect such electron-poor benzylic protecting groups.
- Nucleotides bearing this blocking group may be converted to the intermediate hemiacetal using catalytic reactions known to those skilled in the art such as, for example, those using heavy metal ions such as silver.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
Description
Claims
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03792519A EP1530578B1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing |
EP18157128.2A EP3363809B1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing |
EP19164666.0A EP3587433B1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
JP2005501219A JP2006509040A (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
EP20168283.8A EP3795577A1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
US10/525,401 US7541444B2 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
ES03792519T ES2407681T3 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing. |
AU2003259350A AU2003259350A1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing |
GB0405884A GB2395954A (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
US12/455,397 US7771973B2 (en) | 2002-12-23 | 2009-06-01 | Modified nucleotides |
US12/804,352 US8071739B2 (en) | 2002-08-23 | 2010-07-20 | Modified nucleotides |
US13/281,275 US8597881B2 (en) | 2002-12-23 | 2011-10-25 | Modified nucleotides |
US13/791,575 US9121060B2 (en) | 2002-08-23 | 2013-03-08 | Modified nucleotides |
US14/821,548 US9388464B2 (en) | 2002-08-23 | 2015-08-07 | Modified nucleotides |
US15/179,813 US10513731B2 (en) | 2002-08-23 | 2016-06-10 | Modified nucleotides |
US16/523,810 US20200017908A1 (en) | 2002-08-23 | 2019-07-26 | Modified nucleotides |
CY20201100377T CY1123506T1 (en) | 2002-08-23 | 2020-04-27 | MODIFIED NUCLEOTIDES FOR POLYNUCLEOTIDE SEQUENCES |
CY20201100431T CY1122950T1 (en) | 2002-08-23 | 2020-05-11 | MODIFIED NUCLEOTIDES |
US16/877,442 US20200399692A1 (en) | 2002-08-23 | 2020-05-18 | Modified nucleotides |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/227,131 US7057026B2 (en) | 2001-12-04 | 2002-08-23 | Labelled nucleotides |
US10/227,131 | 2002-08-23 | ||
GB0230037A GB0230037D0 (en) | 2002-12-23 | 2002-12-23 | Modified nucleotides |
GB0230037.4 | 2002-12-23 | ||
GB0303924A GB0303924D0 (en) | 2003-02-20 | 2003-02-20 | Modified nucleotides |
GB0303924.5 | 2003-02-20 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/227,131 Continuation-In-Part US7057026B2 (en) | 2001-12-04 | 2002-08-23 | Labelled nucleotides |
Related Child Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP18157128.2A Previously-Filed-Application EP3363809B1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing |
EP19164666.0A Previously-Filed-Application EP3587433B1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
EP20168283.8A Previously-Filed-Application EP3795577A1 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
US10/525,401 A-371-Of-International US7541444B2 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides |
US12/455,397 Division US7771973B2 (en) | 2002-08-23 | 2009-06-01 | Modified nucleotides |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2004018497A2 true WO2004018497A2 (en) | 2004-03-04 |
WO2004018497A3 WO2004018497A3 (en) | 2004-06-17 |
Family
ID=46324959
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2003/003686 WO2004018497A2 (en) | 2002-08-23 | 2003-08-22 | Modified nucleotides for polynucleotide sequencing |
Country Status (10)
Country | Link |
---|---|
US (9) | US7541444B2 (en) |
EP (6) | EP3002289B1 (en) |
JP (3) | JP2006509040A (en) |
AU (1) | AU2003259350A1 (en) |
CY (1) | CY1120186T1 (en) |
DK (3) | DK3363809T3 (en) |
ES (2) | ES2550513T3 (en) |
GB (1) | GB2395954A (en) |
SI (3) | SI3002289T1 (en) |
WO (1) | WO2004018497A2 (en) |
Cited By (523)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005044836A2 (en) | 2003-11-05 | 2005-05-19 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
JP2005255604A (en) * | 2004-03-11 | 2005-09-22 | Mitsui Chemicals Inc | Method for producing n-acetylcytidine |
WO2007002204A2 (en) * | 2005-06-21 | 2007-01-04 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compostions |
JP2007504817A (en) * | 2003-09-11 | 2007-03-08 | ソレックサ リミテッド | Modified polymerases for improved incorporation of nucleotide analogs |
JP2007056001A (en) * | 2005-07-27 | 2007-03-08 | Gunma Univ | New nucleic acid derivative and method for producing polynucleotide using the same |
WO2007135368A2 (en) * | 2006-05-18 | 2007-11-29 | Solexa Limited | Dye compounds and the use of their labelled conjugates |
US7345159B2 (en) | 2000-10-06 | 2008-03-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
WO2008037568A2 (en) * | 2006-09-04 | 2008-04-03 | Quiatech Ab | Reversible terminators for efficient sequencing by synthesis |
WO2008101024A3 (en) * | 2007-02-13 | 2008-10-09 | Invitrogen Corp | Labeling and detection of nucleic acids |
EP2003214A2 (en) | 2005-02-01 | 2008-12-17 | AB Advanced Genetic Analysis Corporation | Reagents, methods, and libraries for bead-based sequencing |
WO2009116863A2 (en) | 2008-03-17 | 2009-09-24 | Expressive Research B.V. | Expression-linked gene discovery |
US7622279B2 (en) | 2004-03-03 | 2009-11-24 | The Trustees Of Columbia University In The City Of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
WO2010048337A2 (en) | 2008-10-22 | 2010-04-29 | Illumina, Inc. | Preservation of information related to genomic dna methylation |
EP2182079A1 (en) | 2006-07-12 | 2010-05-05 | Keygene N.V. | High throughput physical mapping using AFLP |
WO2010082815A1 (en) | 2009-01-13 | 2010-07-22 | Keygene N.V. | Novel genome sequencing strategies |
EP2233582A1 (en) | 2005-02-01 | 2010-09-29 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
US7893227B2 (en) * | 2006-12-05 | 2011-02-22 | Lasergen, Inc. | 3′-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing |
US7897737B2 (en) * | 2006-12-05 | 2011-03-01 | Lasergen, Inc. | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
US7910335B2 (en) | 2005-10-27 | 2011-03-22 | President And Fellows Of Harvard College | Methods and compositions for labeling nucleic acids |
WO2011050938A1 (en) | 2009-10-26 | 2011-05-05 | Genovoxx Gmbh | Conjugates of nucleotides and method for the application thereof |
WO2011093939A1 (en) | 2010-02-01 | 2011-08-04 | Illumina, Inc. | Focusing methods and optical systems and assemblies using the same |
WO2011112465A1 (en) | 2010-03-06 | 2011-09-15 | Illumina, Inc. | Systems, methods, and apparatuses for detecting optical signals from a sample |
WO2012025250A1 (en) | 2010-08-27 | 2012-03-01 | Illumina Cambridge Ltd. | Methods for paired - end sequencing of polynucleotides |
US8133515B2 (en) | 2007-11-21 | 2012-03-13 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
WO2012034007A2 (en) | 2010-09-10 | 2012-03-15 | Bio-Rad Laboratories, Inc. | Size selection of dna for chromatin analysis |
US8148503B2 (en) | 2008-06-11 | 2012-04-03 | Lasergen, Inc. | Nucleotides and nucleosides and methods for their use in DNA sequencing |
WO2012061036A1 (en) | 2010-11-03 | 2012-05-10 | Illumina, Inc. | Reducing adapter dimer formation |
US8198028B2 (en) | 2008-07-02 | 2012-06-12 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
WO2012096703A1 (en) | 2011-01-10 | 2012-07-19 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US8236532B2 (en) | 2008-12-23 | 2012-08-07 | Illumina, Inc. | Multibase delivery for long reads in sequencing by synthesis protocols |
WO2012106081A2 (en) | 2011-01-31 | 2012-08-09 | Illumina, Inc. | Methods for reducing nucleic acid damage |
DE102012008375A1 (en) | 2011-04-27 | 2012-10-31 | Genovoxx Gmbh | Methods and components for the detection of nucleic acid chains |
WO2012150035A1 (en) | 2011-05-04 | 2012-11-08 | Genovoxx Gmbh | Nucleoside-triphosphate conjugate and methods for the use thereof |
WO2013009175A1 (en) | 2011-07-08 | 2013-01-17 | Keygene N.V. | Sequence based genotyping based on oligonucleotide ligation assays |
EP1530578B1 (en) | 2002-08-23 | 2013-03-13 | Illumina Cambridge Limited | Modified nucleotides for polynucleotide sequencing |
WO2013070627A2 (en) | 2011-11-07 | 2013-05-16 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
WO2013117595A2 (en) | 2012-02-07 | 2013-08-15 | Illumina Cambridge Limited | Targeted enrichment and amplification of nucleic acids on a support |
WO2013126741A1 (en) | 2012-02-24 | 2013-08-29 | Raindance Technologies, Inc. | Labeling and sample preparation for sequencing |
WO2013131962A1 (en) | 2012-03-06 | 2013-09-12 | Illumina Cambridge Limited | Improved methods of nucleic acid sequencing |
EP2644710A1 (en) * | 2008-04-30 | 2013-10-02 | Integrated Dna Technologies, Inc. | RNase-H-based assays utilizing modified RNA monomers |
WO2013148970A1 (en) | 2012-03-30 | 2013-10-03 | Illumina, Inc. | Methods and systems for determining fetal chromosomal abnormalities |
WO2013151622A1 (en) | 2012-04-03 | 2013-10-10 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
US8568979B2 (en) | 2006-10-10 | 2013-10-29 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
EP2669387A1 (en) | 2009-08-25 | 2013-12-04 | Illumina, Inc. | Methods for selecting and amplifying polynucleotides |
WO2013184796A1 (en) | 2012-06-08 | 2013-12-12 | Illumina, Inc. | Polymer coatings |
WO2013188582A1 (en) | 2012-06-15 | 2013-12-19 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US8623628B2 (en) | 2005-05-10 | 2014-01-07 | Illumina, Inc. | Polymerases |
US20140045175A1 (en) * | 2009-04-23 | 2014-02-13 | Intelligent Biosystems, Inc. | Hydroxymethyl Linkers For Labeling Nucleotides |
WO2014066217A1 (en) | 2012-10-23 | 2014-05-01 | Illumina, Inc. | Hla typing using selective amplification and sequencing |
US8759037B2 (en) | 2010-02-23 | 2014-06-24 | Illumina Cambridge Limited | Amplification methods to minimise sequence specific bias |
WO2014108810A2 (en) | 2013-01-09 | 2014-07-17 | Lumina Cambridge Limited | Sample preparation on a solid support |
US8785212B2 (en) | 2006-02-10 | 2014-07-22 | Life Technologies Corporation | Oligosaccharide modification and labeling of proteins |
WO2014116851A2 (en) | 2013-01-25 | 2014-07-31 | Illumina, Inc. | Methods and systems for using a cloud computing environment to share biological related data |
EP2761026A1 (en) * | 2011-09-29 | 2014-08-06 | Illumina, Inc. | Continuous extension and deblocking in reactions for nucleic acid synthesis and sequencing |
WO2014133905A1 (en) | 2013-02-26 | 2014-09-04 | Illumina, Inc. | Gel patterned surfaces |
WO2014135221A1 (en) | 2013-03-08 | 2014-09-12 | Illumina Cambridge Ltd | Polymethine compounds and their use as fluorescent labels |
WO2014135669A1 (en) | 2013-03-08 | 2014-09-12 | Roche Diagnostics Gmbh | Egfr mutation blood testing |
WO2014135223A1 (en) | 2013-03-08 | 2014-09-12 | Illumina Cambridge Ltd | Rhodamine compounds and their use as fluorescent labels |
WO2014142841A1 (en) | 2013-03-13 | 2014-09-18 | Illumina, Inc. | Multilayer fluidic devices and methods for their fabrication |
WO2014142921A1 (en) | 2013-03-14 | 2014-09-18 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
WO2014139596A1 (en) * | 2013-03-15 | 2014-09-18 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
WO2014144569A1 (en) | 2013-03-15 | 2014-09-18 | Illumina, Inc. | Super resolution imaging |
US8889860B2 (en) | 2011-09-13 | 2014-11-18 | Lasergen, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
DE202014006405U1 (en) | 2013-08-08 | 2014-12-08 | Illumina, Inc. | Fluid system for reagent delivery to a flow cell |
US8911948B2 (en) | 2008-04-30 | 2014-12-16 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
US8921073B2 (en) | 2006-06-23 | 2014-12-30 | Illumina, Inc. | Devices and systems for creation of DNA cluster arrays |
WO2015002789A1 (en) | 2013-07-03 | 2015-01-08 | Illumina, Inc. | Sequencing by orthogonal synthesis |
WO2015002813A1 (en) | 2013-07-01 | 2015-01-08 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
US9017623B2 (en) | 2007-02-06 | 2015-04-28 | Raindance Technologies, Inc. | Manipulation of fluids and reactions in microfluidic systems |
US9029083B2 (en) | 2004-10-08 | 2015-05-12 | Medical Research Council | Vitro evolution in microfluidic systems |
US9051612B2 (en) | 2006-09-28 | 2015-06-09 | Illumina, Inc. | Compositions and methods for nucleotide sequencing |
WO2015084985A2 (en) | 2013-12-03 | 2015-06-11 | Illumina, Inc. | Methods and systems for analyzing image data |
WO2015095226A2 (en) | 2013-12-20 | 2015-06-25 | Illumina, Inc. | Preserving genomic connectivity information in fragmented genomic dna samples |
US9068699B2 (en) | 2007-04-19 | 2015-06-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
WO2015100373A2 (en) | 2013-12-23 | 2015-07-02 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
US9074242B2 (en) | 2010-02-12 | 2015-07-07 | Raindance Technologies, Inc. | Digital analyte analysis |
WO2015103225A1 (en) | 2013-12-31 | 2015-07-09 | Illumina, Inc. | Addressable flow cell using patterned electrodes |
WO2015108663A1 (en) | 2014-01-16 | 2015-07-23 | Illumina, Inc. | Amplicon preparation and sequencing on solid supports |
WO2015106941A1 (en) | 2014-01-16 | 2015-07-23 | Illumina Cambridge Limited | Polynucleotide modification on solid support |
US9092401B2 (en) | 2012-10-31 | 2015-07-28 | Counsyl, Inc. | System and methods for detecting genetic variation |
US9115387B2 (en) | 2013-03-14 | 2015-08-25 | Good Start Genetics, Inc. | Methods for analyzing nucleic acids |
EP2918686A1 (en) | 2005-11-25 | 2015-09-16 | Illumina Cambridge Limited | Preparation of nucleic acid templates for solid phase amplification |
WO2015175832A1 (en) | 2014-05-16 | 2015-11-19 | Illumina, Inc. | Nucleic acid synthesis techniques |
WO2015183871A1 (en) | 2014-05-27 | 2015-12-03 | Illumina, Inc. | Systems and methods for biochemical analysis including a base instrument and a removable cartridge |
WO2015200609A1 (en) | 2014-06-26 | 2015-12-30 | Illumina, Inc. | Library preparation of tagged nucleic acid using single tube add-on protocol |
WO2015200693A1 (en) | 2014-06-27 | 2015-12-30 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US9228233B2 (en) | 2011-10-17 | 2016-01-05 | Good Start Genetics, Inc. | Analysis methods |
EP2963127A1 (en) | 2006-04-04 | 2016-01-06 | Keygene N.V. | High throughput detection of molecular markers based on restriction fragments |
WO2016003814A1 (en) | 2014-06-30 | 2016-01-07 | Illumina, Inc. | Methods and compositions using one-sided transposition |
WO2016014409A1 (en) | 2014-07-21 | 2016-01-28 | Illumina, Inc. | Polynucleotide enrichment using crispr-cas systems |
WO2016026924A1 (en) | 2014-08-21 | 2016-02-25 | Illumina Cambridge Limited | Reversible surface functionalization |
WO2016040602A1 (en) | 2014-09-11 | 2016-03-17 | Epicentre Technologies Corporation | Reduced representation bisulfite sequencing using uracil n-glycosylase (ung) and endonuclease iv |
WO2016040607A1 (en) | 2014-09-12 | 2016-03-17 | Illumina, Inc. | Compositions, systems, and methods for detecting the presence of polymer subunits using chemiluminescence |
WO2016044233A1 (en) | 2014-09-18 | 2016-03-24 | Illumina, Inc. | Methods and systems for analyzing nucleic acid sequencing data |
US9298804B2 (en) | 2012-04-09 | 2016-03-29 | Good Start Genetics, Inc. | Variant database |
WO2016054096A1 (en) | 2014-09-30 | 2016-04-07 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
WO2016061484A2 (en) | 2014-10-16 | 2016-04-21 | Illumina, Inc. | Optical scanning systems for in situ genetic analysis |
WO2016073237A1 (en) | 2014-11-05 | 2016-05-12 | Illumina Cambridge Limited | Reducing dna damage during sample preparation and sequencing using siderophore chelators |
US9434988B2 (en) | 2008-04-30 | 2016-09-06 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
WO2016139477A1 (en) * | 2015-03-03 | 2016-09-09 | Nuclera Nucleics Ltd | A process for the preparation of nucleic acid by means of 3'-o-azidomethyl nucleotide triphosphate |
US9453258B2 (en) | 2011-09-23 | 2016-09-27 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
EP1907583B1 (en) | 2005-06-15 | 2016-10-05 | Complete Genomics Inc. | Single molecule arrays for genetic and chemical analysis |
WO2016162309A1 (en) | 2015-04-10 | 2016-10-13 | Spatial Transcriptomics Ab | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
WO2016168386A1 (en) | 2015-04-14 | 2016-10-20 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
WO2016183029A1 (en) | 2015-05-11 | 2016-11-17 | Illumina, Inc. | Platform for discovery and analysis of therapeutic agents |
WO2016196210A2 (en) | 2015-05-29 | 2016-12-08 | Illumina, Inc. | Sample carrier and assay system for conducting designated reactions |
WO2016196358A1 (en) | 2015-05-29 | 2016-12-08 | Epicentre Technologies Corporation | Methods of analyzing nucleic acids |
US9535920B2 (en) | 2013-06-03 | 2017-01-03 | Good Start Genetics, Inc. | Methods and systems for storing sequence read data |
WO2017009663A1 (en) * | 2015-07-15 | 2017-01-19 | Nuclera Nucleics Ltd | Azidomethyl ether deprotection method |
WO2017015018A1 (en) | 2015-07-17 | 2017-01-26 | Illumina, Inc. | Polymer sheets for sequencing applications |
WO2017019456A2 (en) | 2015-07-27 | 2017-02-02 | Illumina, Inc. | Spatial mapping of nucleic acid sequence information |
WO2017019278A1 (en) | 2015-07-30 | 2017-02-02 | Illumina, Inc. | Orthogonal deblocking of nucleotides |
DE202017100081U1 (en) | 2016-01-11 | 2017-03-19 | Illumina, Inc. | Detection device with a microfluorometer, a fluidic system and a flow cell detent module |
US9605310B2 (en) | 2001-12-04 | 2017-03-28 | Illumina Cambridge Limited | Labelled nucleotides |
US9624539B2 (en) | 2011-05-23 | 2017-04-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using Raman and infrared spectroscopy detection |
US9670535B2 (en) | 2011-10-28 | 2017-06-06 | Illumina, Inc. | Microarray fabrication system and method |
US9670539B2 (en) | 2007-10-19 | 2017-06-06 | The Trustees Of Columbia University In The City Of New York | Synthesis of cleavable fluorescent nucleotides as reversible terminators for DNA sequencing by synthesis |
US9708358B2 (en) | 2000-10-06 | 2017-07-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9708655B2 (en) | 2014-06-03 | 2017-07-18 | Illumina, Inc. | Compositions, systems, and methods for detecting events using tethers anchored to or adjacent to nanopores |
US9765391B2 (en) | 2005-07-20 | 2017-09-19 | Illumina Cambridge Limited | Methods for sequencing a polynucleotide template |
WO2017165703A1 (en) | 2016-03-24 | 2017-09-28 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
WO2017168332A1 (en) | 2016-03-28 | 2017-10-05 | Boreal Genomics, Inc. | Linked duplex target capture |
WO2017177017A1 (en) | 2016-04-07 | 2017-10-12 | Omniome, Inc. | Methods of quantifying target nucleic acids and identifying sequence variants |
WO2017184997A1 (en) | 2016-04-22 | 2017-10-26 | Illumina, Inc. | Photonic stucture-based devices and compositions for use in luminescent imaging of multiple sites within a pixel, and methods of using the same |
WO2017185026A1 (en) * | 2016-04-22 | 2017-10-26 | Complete Genomics, Inc. | Reversibly blocked nucleoside analogues and their use |
US9815916B2 (en) | 2014-10-31 | 2017-11-14 | Illumina Cambridge Limited | Polymers and DNA copolymer coatings |
EP3243937A1 (en) | 2012-07-17 | 2017-11-15 | Counsyl, Inc. | System and methods for detecting genetic variation |
WO2017197027A1 (en) | 2016-05-11 | 2017-11-16 | Illumina, Inc. | Polynucleotide enrichment and amplification using argonaute systems |
WO2017201198A1 (en) | 2016-05-18 | 2017-11-23 | Illumina, Inc. | Self assembled patterning using patterned hydrophobic surfaces |
US9839890B2 (en) | 2004-03-31 | 2017-12-12 | National Science Foundation | Compartmentalised combinatorial chemistry by microfluidic control |
US9857303B2 (en) | 2003-03-31 | 2018-01-02 | Medical Research Council | Selection by compartmentalised screening |
US9868947B2 (en) | 2015-05-04 | 2018-01-16 | Washington University | Compositions and methods for the construction of a random allelic series |
WO2018018008A1 (en) | 2016-07-22 | 2018-01-25 | Oregon Health & Science University | Single cell whole genome libraries and combinatorial indexing methods of making thereof |
WO2018060482A1 (en) | 2016-09-30 | 2018-04-05 | Illumina Cambridge Limited | New fluorescent dyes and their uses as biomarkers |
WO2018064116A1 (en) | 2016-09-28 | 2018-04-05 | Illumina, Inc. | Methods and systems for data compression |
EP3308860A1 (en) | 2016-10-14 | 2018-04-18 | Illumina, Inc. | Cartridge assembly |
WO2018075785A1 (en) | 2016-10-19 | 2018-04-26 | Illumina, Inc. | Methods for chemical ligation of nucleic acids |
US9976174B2 (en) | 2015-03-24 | 2018-05-22 | Illumina Cambridge Limited | Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis |
WO2018093780A1 (en) | 2016-11-16 | 2018-05-24 | Illumina, Inc. | Validation methods and systems for sequence variant calls |
US10000799B2 (en) | 2014-11-04 | 2018-06-19 | Boreal Genomics, Inc. | Methods of sequencing with linked fragments |
WO2018119063A1 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Arrays with quality control tracers |
WO2018119053A1 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Arrays including a resin film and a patterned polymer layer |
WO2018114710A1 (en) | 2016-12-22 | 2018-06-28 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
WO2018119057A2 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Array including sequencing primer and non-sequencing entity |
WO2018125759A1 (en) | 2016-12-30 | 2018-07-05 | Omniome, Inc. | Method and system employing distinguishable polymerases for detecting ternary complexes and identifying cognate nucleotides |
WO2018128544A1 (en) | 2017-01-06 | 2018-07-12 | Agendia N.V. | Biomarkers for selecting patient groups, and uses thereof. |
WO2018129314A1 (en) | 2017-01-06 | 2018-07-12 | Illumina, Inc. | Phasing correction |
WO2018128777A1 (en) | 2017-01-05 | 2018-07-12 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
WO2018132389A1 (en) | 2017-01-10 | 2018-07-19 | Omniome, Inc. | Polymerases engineered to reduce nucleotide-independent dna binding |
WO2018136117A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Allele-specific capture of nucleic acids |
WO2018136416A1 (en) | 2017-01-17 | 2018-07-26 | Illumina, Inc. | Oncogenic splice variant determination |
WO2018136487A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Process for cognate nucleotide detection in a nucleic acid sequencing workflow |
WO2018136118A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Genotyping by polymerase binding |
US10036063B2 (en) | 2009-07-24 | 2018-07-31 | Illumina, Inc. | Method for sequencing a polynucleotide template |
WO2018144567A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials in non-rectilinear layouts |
WO2018144574A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials having offset layouts |
WO2018144563A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials of non-closed shapes |
WO2018148727A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from 9°n |
WO2018148723A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from pyrococcus abyssi |
WO2018148724A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from pyrococcus furiosus |
WO2018148726A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from phage t4 |
US10052605B2 (en) | 2003-03-31 | 2018-08-21 | Medical Research Council | Method of synthesis and testing of combinatorial libraries using microcapsules |
WO2018151601A1 (en) | 2017-02-17 | 2018-08-23 | Stichting Vumc | Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets |
WO2018152162A1 (en) | 2017-02-15 | 2018-08-23 | Omniome, Inc. | Distinguishing sequences by detecting polymerase dissociation |
WO2018156519A1 (en) | 2017-02-21 | 2018-08-30 | Illumina Inc. | Tagmentation using immobilized transposomes with linkers |
US10066259B2 (en) | 2015-01-06 | 2018-09-04 | Good Start Genetics, Inc. | Screening for structural variants |
EP3373174A1 (en) | 2006-03-31 | 2018-09-12 | Illumina, Inc. | Systems and devices for sequence by synthesis analysis |
WO2018170340A1 (en) | 2017-03-15 | 2018-09-20 | The Broad Institute, Inc. | Crispr effector system based diagnostics for virus detection |
WO2018175258A1 (en) | 2017-03-20 | 2018-09-27 | Illumina, Inc. | Methods and compositions for preparing nuclelic acid libraries |
WO2018175798A1 (en) | 2017-03-24 | 2018-09-27 | Life Technologies Corporation | Polynucleotide adapters and methods of use thereof |
WO2018197945A1 (en) | 2017-04-23 | 2018-11-01 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200709A1 (en) | 2017-04-25 | 2018-11-01 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
WO2018197950A1 (en) | 2017-04-23 | 2018-11-01 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200386A1 (en) | 2017-04-23 | 2018-11-01 | Illumina, Inc. | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200380A1 (en) | 2017-04-23 | 2018-11-01 | Illumina, Inc. | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018204423A1 (en) | 2017-05-01 | 2018-11-08 | Illumina, Inc. | Optimal index sequences for multiplex massively parallel sequencing |
WO2018208699A1 (en) | 2017-05-08 | 2018-11-15 | Illumina, Inc. | Universal short adapters for indexing of polynucleotide samples |
US10138510B2 (en) | 2008-05-16 | 2018-11-27 | Life Technologies Corporation | Dual labeling methods for measuring cellular proliferation |
WO2018226708A1 (en) | 2017-06-07 | 2018-12-13 | Oregon Health & Science University | Single cell whole genome libraries for methylation sequencing |
WO2018236631A1 (en) | 2017-06-20 | 2018-12-27 | Illumina, Inc. | Methods and compositions for addressing inefficiencies in amplification reactions |
WO2019018366A1 (en) | 2017-07-18 | 2019-01-24 | Omniome, Inc. | Method of chemically modifying plastic surfaces |
US10190162B2 (en) | 2014-10-23 | 2019-01-29 | Complete Genomics, Inc. | Signal confinement sequencing (SCS) and nucleotide analogues for signal confinement sequencing |
GB201820341D0 (en) | 2018-12-13 | 2019-01-30 | 10X Genomics Inc | Method for transposase-mediated spatial tagging and analysing genomic DNA in a biological specimen |
GB201820300D0 (en) | 2018-12-13 | 2019-01-30 | 10X Genomics Inc | Method for spatial tagging and analysing genomic DNA in a biological specimen |
EP3438286A1 (en) | 2012-05-02 | 2019-02-06 | Ibis Biosciences, Inc. | Dna sequencing |
EP3438285A1 (en) | 2012-05-02 | 2019-02-06 | Ibis Biosciences, Inc. | Dna sequencing |
WO2019027767A1 (en) | 2017-07-31 | 2019-02-07 | Illumina Inc. | Sequencing system with multiplexed biological sample aggregation |
WO2019028166A1 (en) | 2017-08-01 | 2019-02-07 | Illumina, Inc. | Hydrogel beads for nucleotide sequencing |
WO2019023951A1 (en) | 2017-08-01 | 2019-02-07 | 深圳华大智造科技有限公司 | Nucleic acid sequencing method |
WO2019028047A1 (en) | 2017-08-01 | 2019-02-07 | Illumina, Inc | Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells |
US10202642B2 (en) | 2012-05-02 | 2019-02-12 | Ibis Biosciences, Inc. | DNA sequencing |
WO2019035897A1 (en) | 2017-08-15 | 2019-02-21 | Omniome, Inc. | Scanning apparatus and methods useful for detection of chemical and biological analytes |
US10227585B2 (en) | 2008-09-12 | 2019-03-12 | University Of Washington | Sequence tag directed subassembly of short sequencing reads into long sequencing reads |
US10227635B2 (en) | 2012-04-16 | 2019-03-12 | Molecular Loop Biosolutions, Llc | Capture reactions |
WO2019055715A1 (en) | 2017-09-15 | 2019-03-21 | Illumina, Inc. | Universal short adapters with variable length non-random unique molecular identifiers |
US10239909B2 (en) | 2015-05-22 | 2019-03-26 | Illumina Cambridge Limited | Polymethine compounds with long stokes shifts and their use as fluorescent labels |
EP3460075A1 (en) | 2014-07-15 | 2019-03-27 | Illumina, Inc. | Biochemically activated electronic device |
US10246705B2 (en) | 2011-02-10 | 2019-04-02 | Ilumina, Inc. | Linking sequence reads using paired code tags |
US10249038B2 (en) | 2013-03-15 | 2019-04-02 | Qiagen Sciences, Llc | Flow cell alignment methods and systems |
US10253352B2 (en) | 2015-11-17 | 2019-04-09 | Omniome, Inc. | Methods for determining sequence profiles |
US10260094B2 (en) | 2007-10-19 | 2019-04-16 | The Trustees Of Columbia University In The City Of New York | DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified nucleotide terminators |
WO2019079182A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Semi-supervised learning for training an ensemble of deep convolutional neural networks |
WO2019079198A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Deep learning-based splice site classification |
WO2019136388A1 (en) | 2018-01-08 | 2019-07-11 | Illumina, Inc. | Systems and devices for high-throughput sequencing with semiconductor-based detection |
US10350570B2 (en) | 2014-12-15 | 2019-07-16 | Illumina, Inc. | Compositions and methods for single molecular placement on a substrate |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
WO2019140402A1 (en) | 2018-01-15 | 2019-07-18 | Illumina, Inc. | Deep learning-based variant classifier |
WO2019148206A1 (en) | 2018-01-29 | 2019-08-01 | The Broad Institute, Inc. | Crispr effector system based diagnostics |
WO2019160820A1 (en) | 2018-02-13 | 2019-08-22 | Illumina, Inc. | Dna sequencing using hydrogel beads |
US10400272B1 (en) | 2018-04-26 | 2019-09-03 | Omniome, Inc. | Methods and compositions for stabilizing nucleic acid-nucleotide-polymerase complexes |
US10428367B2 (en) | 2012-04-11 | 2019-10-01 | Illumina, Inc. | Portable genetic detection and analysis system and method |
US10429399B2 (en) | 2014-09-24 | 2019-10-01 | Good Start Genetics, Inc. | Process control for increased robustness of genetic assays |
WO2019195225A1 (en) | 2018-04-02 | 2019-10-10 | Illumina, Inc. | Compositions and methods for making controls for sequence-based genetic testing |
US10443087B2 (en) | 2014-06-13 | 2019-10-15 | Illumina Cambridge Limited | Methods and compositions for preparing sequencing libraries |
WO2019200338A1 (en) | 2018-04-12 | 2019-10-17 | Illumina, Inc. | Variant classifier based on deep neural networks |
US10450598B2 (en) | 2015-09-11 | 2019-10-22 | Illumina, Inc. | Systems and methods for obtaining a droplet having a designated concentration of a substance-of-interest |
WO2019204229A1 (en) | 2018-04-20 | 2019-10-24 | Illumina, Inc. | Methods of encapsulating single cells, the encapsulated cells and uses thereof |
WO2019203986A1 (en) | 2018-04-19 | 2019-10-24 | Omniome, Inc. | Improving accuracy of base calls in nucleic acid sequencing methods |
US10457936B2 (en) | 2011-02-02 | 2019-10-29 | University Of Washington Through Its Center For Commercialization | Massively parallel contiguity mapping |
US10465232B1 (en) | 2015-10-08 | 2019-11-05 | Trace Genomics, Inc. | Methods for quantifying efficiency of nucleic acid extraction and detection |
EP3564252A1 (en) | 2014-08-08 | 2019-11-06 | Illumina Cambridge Limited | Modified nucleotide linkers |
US10480022B2 (en) | 2010-04-05 | 2019-11-19 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
WO2019222264A1 (en) | 2018-05-15 | 2019-11-21 | Illumina, Inc. | Compositions and methods for chemical cleavage and deprotection of surface-bound oligonucleotides |
US10487102B2 (en) | 2002-08-23 | 2019-11-26 | Illumina Cambridge Limited | Labelled nucleotides |
WO2019227015A1 (en) | 2018-05-25 | 2019-11-28 | Illumina, Inc. | Circulating rna signatures specific to preeclampsia |
WO2019231568A1 (en) | 2018-05-31 | 2019-12-05 | Omniome, Inc. | Increased signal to noise in nucleic acid sequencing |
US10520500B2 (en) | 2009-10-09 | 2019-12-31 | Abdeslam El Harrak | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
US10526648B2 (en) | 2017-07-12 | 2020-01-07 | Illumina Cambridge Limited | Short pendant arm linkers for nucleotides in sequencing applications |
US10533998B2 (en) | 2008-07-18 | 2020-01-14 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
WO2020014280A1 (en) | 2018-07-11 | 2020-01-16 | Illumina, Inc. | DEEP LEARNING-BASED FRAMEWORK FOR IDENTIFYING SEQUENCE PATTERNS THAT CAUSE SEQUENCE-SPECIFIC ERRORS (SSEs) |
US10540783B2 (en) | 2013-11-01 | 2020-01-21 | Illumina, Inc. | Image analysis useful for patterned objects |
WO2020023362A1 (en) | 2018-07-24 | 2020-01-30 | Omniome, Inc. | Serial formation of ternary complex species |
WO2020022891A2 (en) | 2018-07-26 | 2020-01-30 | Stichting Vumc | Biomarkers for atrial fibrillation |
US10557133B2 (en) | 2013-03-13 | 2020-02-11 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
WO2020036991A1 (en) | 2018-08-15 | 2020-02-20 | Illumina, Inc. | Compositions and methods for improving library enrichment |
US10576471B2 (en) | 2015-03-20 | 2020-03-03 | Illumina, Inc. | Fluidics cartridge for use in the vertical or substantially vertical position |
US10577649B2 (en) | 2014-11-11 | 2020-03-03 | Illumina, Inc. | Polynucleotide amplification using CRISPR-Cas systems |
US10590464B2 (en) | 2015-05-29 | 2020-03-17 | Illumina Cambridge Limited | Enhanced utilization of surface primers in clusters |
DE202019106695U1 (en) | 2019-12-02 | 2020-03-19 | Omniome, Inc. | System for sequencing nucleic acids in fluid foam |
DE202019106694U1 (en) | 2019-12-02 | 2020-03-19 | Omniome, Inc. | System for sequencing nucleic acids in fluid foam |
WO2020060811A1 (en) | 2018-09-17 | 2020-03-26 | Omniome, Inc. | Engineered polymerases for improved sequencing |
US10604799B2 (en) | 2012-04-04 | 2020-03-31 | Molecular Loop Biosolutions, Llc | Sequence assembly |
US10619204B2 (en) | 2014-11-11 | 2020-04-14 | Illumina Cambridge Limited | Methods and arrays for producing and sequencing monoclonal clusters of nucleic acid |
WO2020081122A1 (en) | 2018-10-15 | 2020-04-23 | Illumina, Inc. | Deep learning-based techniques for pre-training deep convolutional neural networks |
WO2020086843A1 (en) | 2018-10-26 | 2020-04-30 | Illumina, Inc. | Modulating polymer beads for dna processing |
WO2020092830A1 (en) | 2018-10-31 | 2020-05-07 | Illumina, Inc. | Polymerases, compositions, and methods of use |
US10648026B2 (en) | 2013-03-15 | 2020-05-12 | The Trustees Of Columbia University In The City Of New York | Raman cluster tagged molecules for biological imaging |
US10648022B2 (en) | 2015-06-03 | 2020-05-12 | Illumina, Inc. | Compositions, systems, and methods for sequencing polynucleotides using tethers anchored to polymerases adjacent to nanopores |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
WO2020093261A1 (en) | 2018-11-07 | 2020-05-14 | 深圳华大智造极创科技有限公司 | Method for sequencing polynucleotides |
US10656368B1 (en) | 2019-07-24 | 2020-05-19 | Omniome, Inc. | Method and system for biological imaging using a wide field objective lens |
WO2020112604A2 (en) | 2018-11-30 | 2020-06-04 | Illumina, Inc. | Analysis of multiple analytes using a single assay |
EP3663290A1 (en) | 2015-09-25 | 2020-06-10 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
WO2020117968A2 (en) | 2018-12-05 | 2020-06-11 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2020114918A1 (en) | 2018-12-05 | 2020-06-11 | Illumina Cambridge Limited | Methods and compositions for cluster generation by bridge amplification |
WO2020117653A1 (en) | 2018-12-04 | 2020-06-11 | Omniome, Inc. | Mixed-phase fluids for nucleic acid sequencing and other analytical assays |
WO2020120179A1 (en) | 2018-12-14 | 2020-06-18 | Illumina Cambridge Limited | Decreasing phasing with unlabeled nucleotides during sequencing |
EP3670672A1 (en) | 2006-10-06 | 2020-06-24 | Illumina Cambridge Limited | Method for sequencing a polynucleotide template |
WO2020132350A2 (en) | 2018-12-20 | 2020-06-25 | Omniome, Inc. | Temperature control for analysis of nucleic acids and other analytes |
WO2020126602A1 (en) | 2018-12-18 | 2020-06-25 | Illumina Cambridge Limited | Methods and compositions for paired end sequencing using a single surface primer |
WO2020132103A1 (en) | 2018-12-19 | 2020-06-25 | Illumina, Inc. | Methods for improving polynucleotide cluster clonality priority |
WO2020126595A1 (en) | 2018-12-17 | 2020-06-25 | Illumina Cambridge Limited | Primer oligonucleotide for sequencing |
WO2020131759A1 (en) | 2018-12-19 | 2020-06-25 | Roche Diagnostics Gmbh | 3' protected nucleotides |
WO2020126593A1 (en) | 2018-12-17 | 2020-06-25 | Illumina Cambridge Limited | Compositions for use in polyunucleotide sequencing |
WO2020136170A2 (en) | 2018-12-26 | 2020-07-02 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3'-hydroxy blocking groups |
WO2020141464A1 (en) | 2019-01-03 | 2020-07-09 | Boreal Genomics, Inc. | Linked target capture |
EP3680333A1 (en) | 2014-04-29 | 2020-07-15 | Illumina, Inc. | Multiplexed single cell expression analysis using template switch and tagmentation |
WO2020144373A1 (en) | 2019-01-11 | 2020-07-16 | Illumina Cambridge Limited | Complex surface-bound transposome complexes |
US10737267B2 (en) | 2017-04-04 | 2020-08-11 | Omniome, Inc. | Fluidic apparatus and methods useful for chemical and biological reactions |
WO2020167574A1 (en) | 2019-02-14 | 2020-08-20 | Omniome, Inc. | Mitigating adverse impacts of detection systems on nucleic acids and other biological analytes |
EP3699577A2 (en) | 2012-08-20 | 2020-08-26 | Illumina, Inc. | System for fluorescence lifetime based sequencing |
EP3699289A1 (en) | 2014-06-09 | 2020-08-26 | Illumina Cambridge Limited | Sample preparation for nucleic acid amplification |
EP3698874A1 (en) | 2014-03-11 | 2020-08-26 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making the same |
EP3699283A1 (en) | 2014-10-20 | 2020-08-26 | Molecular Assemblies Inc. | Modified template-independent enzymes for polydeoxynucleotide systhesis |
WO2020178231A1 (en) | 2019-03-01 | 2020-09-10 | Illumina, Inc. | Multiplexed fluorescent detection of analytes |
WO2020178162A1 (en) | 2019-03-01 | 2020-09-10 | Illumina Cambridge Limited | Exocyclic amine-substituted coumarin compounds and their uses as fluorescent labels |
WO2020180778A1 (en) | 2019-03-01 | 2020-09-10 | Illumina, Inc. | High-throughput single-nuclei and single-cell libraries and methods of making and of using |
WO2020178165A1 (en) | 2019-03-01 | 2020-09-10 | Illumina Cambridge Limited | Tertiary amine substituted coumarin compounds and their uses as fluorescent labels |
NL2023327B1 (en) | 2019-03-01 | 2020-09-17 | Illumina Inc | Multiplexed fluorescent detection of analytes |
WO2020191391A2 (en) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Artificial intelligence-based sequencing |
NL2023314B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based quality scoring |
NL2023312B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based base calling |
NL2023311B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based generation of sequencing metadata |
NL2023316B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based sequencing |
NL2023310B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Training data generation for artificial intelligence-based sequencing |
US10787698B2 (en) | 2011-06-09 | 2020-09-29 | Illumina, Inc. | Patterned flow-cells useful for nucleic acid analysis |
WO2020193765A1 (en) | 2019-03-28 | 2020-10-01 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing using photoswitchable labels |
US10808282B2 (en) | 2015-07-07 | 2020-10-20 | Illumina, Inc. | Selective surface patterning via nanoimprinting |
EP3725893A1 (en) | 2015-02-10 | 2020-10-21 | Illumina, Inc. | Compositions for analyzing cellular components |
EP3736281A1 (en) | 2011-02-18 | 2020-11-11 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US10837040B2 (en) | 2014-04-17 | 2020-11-17 | Dna Script | Method for synthesizing nucleic acids, in particular long nucleic acids, use of said method and kit for implementing said method |
US10837883B2 (en) | 2009-12-23 | 2020-11-17 | Bio-Rad Laboratories, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
WO2020232410A1 (en) | 2019-05-16 | 2020-11-19 | Illumina, Inc. | Base calling using convolutions |
WO2020227953A1 (en) | 2019-05-15 | 2020-11-19 | 深圳华大智造极创科技有限公司 | Single-channel sequencing method based on self-luminescence |
US10844428B2 (en) | 2015-04-28 | 2020-11-24 | Illumina, Inc. | Error suppression in sequenced DNA fragments using redundant reads with unique molecular indices (UMIS) |
US10844429B2 (en) | 2017-01-18 | 2020-11-24 | Illumina, Inc. | Methods and systems for generation and error-correction of unique molecular index sets with heterogeneous molecular lengths |
US10851414B2 (en) | 2013-10-18 | 2020-12-01 | Good Start Genetics, Inc. | Methods for determining carrier status |
WO2020252186A1 (en) | 2019-06-11 | 2020-12-17 | Omniome, Inc. | Calibrated focus sensing |
US10894981B2 (en) | 2015-10-13 | 2021-01-19 | Japan Agency For Marine-Earth Science And Technology | Method for fragmenting double-stranded RNA and use of the same |
WO2021009494A1 (en) | 2019-07-12 | 2021-01-21 | Illumina Cambridge Limited | Nucleic acid library preparation using electrophoresis |
WO2021008805A1 (en) | 2019-07-12 | 2021-01-21 | Illumina Cambridge Limited | Compositions and methods for preparing nucleic acid sequencing libraries using crispr/cas9 immobilized on a solid support |
US10906044B2 (en) | 2015-09-02 | 2021-02-02 | Illumina Cambridge Limited | Methods of improving droplet operations in fluidic systems with a filler fluid including a surface regenerative silane |
EP3438116B1 (en) | 2002-08-23 | 2021-02-17 | Illumina Cambridge Limited | Labelled nucleotides |
EP3783109A1 (en) | 2015-03-31 | 2021-02-24 | Illumina Cambridge Limited | Surface concatamerization of templates |
WO2021031109A1 (en) | 2019-08-20 | 2021-02-25 | 深圳华大智造极创科技有限公司 | Method for sequencing polynucleotides on basis of optical signal dynamics of luminescent label and secondary luminescent signal |
WO2021050962A1 (en) | 2019-09-11 | 2021-03-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cancer detection and classification |
WO2021050681A1 (en) | 2019-09-10 | 2021-03-18 | Omniome, Inc. | Reversible modification of nucleotides |
US10961573B2 (en) | 2016-03-28 | 2021-03-30 | Boreal Genomics, Inc. | Linked duplex target capture |
EP3798321A1 (en) | 2015-12-17 | 2021-03-31 | Illumina, Inc. | Distinguishing methylation levels in complex biological samples |
US10976334B2 (en) | 2015-08-24 | 2021-04-13 | Illumina, Inc. | In-line pressure accumulator and flow-control system for biological or chemical assays |
WO2021076152A1 (en) | 2019-10-18 | 2021-04-22 | Omniome, Inc. | Methods and compositions for capping nucleic acids |
US10995111B2 (en) | 2003-08-22 | 2021-05-04 | Illumina Cambridge Limited | Labelled nucleotides |
WO2021092431A1 (en) | 2019-11-08 | 2021-05-14 | Omniome, Inc. | Engineered polymerases for improved sequencing by binding |
WO2021102236A1 (en) | 2019-11-22 | 2021-05-27 | Illumina, Inc. | Circulating rna signatures specific to preeclampsia |
US11021740B2 (en) | 2017-03-15 | 2021-06-01 | The Broad Institute, Inc. | Devices for CRISPR effector system based diagnostics |
EP3828167A1 (en) | 2014-05-07 | 2021-06-02 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
WO2021104845A1 (en) | 2019-11-27 | 2021-06-03 | Illumina Cambridge Limited | Cyclooctatetraene containing dyes and compositions |
EP3831484A1 (en) | 2016-03-28 | 2021-06-09 | Illumina, Inc. | Multi-plane microarrays |
WO2021113287A1 (en) | 2019-12-04 | 2021-06-10 | Illumina, Inc. | Preparation of dna sequencing libraries for detection of dna pathogens in plasma |
US11034942B1 (en) | 2020-02-27 | 2021-06-15 | Singular Genomics Systems, Inc. | Modified pyrococcus polymerases and uses thereof |
WO2021118349A1 (en) | 2019-12-10 | 2021-06-17 | Prinses Máxima Centrum Voor Kinderoncologie B.V. | Methods of typing germ cell tumors |
US11041852B2 (en) | 2010-12-23 | 2021-06-22 | Molecular Loop Biosciences, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
US11041203B2 (en) | 2013-10-18 | 2021-06-22 | Molecular Loop Biosolutions, Inc. | Methods for assessing a genomic region of a subject |
WO2021127436A2 (en) | 2019-12-19 | 2021-06-24 | Illumina, Inc. | High-throughput single-cell libraries and methods of making and of using |
WO2021123074A1 (en) | 2019-12-18 | 2021-06-24 | F. Hoffmann-La Roche Ag | Methods of sequencing by synthesis using a consecutive labeling scheme |
WO2021133685A1 (en) | 2019-12-23 | 2021-07-01 | Singular Genomics Systems, Inc. | Methods for long read sequencing |
US11053548B2 (en) | 2014-05-12 | 2021-07-06 | Good Start Genetics, Inc. | Methods for detecting aneuploidy |
WO2021138094A1 (en) | 2019-12-31 | 2021-07-08 | Singular Genomics Systems, Inc. | Polynucleotide barcodes for long read sequencing |
US11059849B2 (en) | 2014-09-02 | 2021-07-13 | Dna Script | Modified nucleotides for synthesis of nucleic acids, a kit containing such nucleotides and their use for the production of synthetic nucleic acid sequences or genes |
EP3854884A1 (en) | 2015-08-14 | 2021-07-28 | Illumina, Inc. | Systems and methods using magnetically-responsive sensors for determining a genetic characteristic |
US11077415B2 (en) | 2011-02-11 | 2021-08-03 | Bio-Rad Laboratories, Inc. | Methods for forming mixed droplets |
WO2021158511A1 (en) | 2020-02-04 | 2021-08-12 | Omniome, Inc. | Flow cells and methods for their manufacture and use |
US11098356B2 (en) | 2008-01-28 | 2021-08-24 | Complete Genomics, Inc. | Methods and compositions for nucleic acid sequencing |
US11098353B2 (en) | 2006-12-01 | 2021-08-24 | The Trustees Of Columbia University In The City Of New York | Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators |
WO2021168018A1 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Hardware execution and acceleration of artificial intelligence-based base caller |
WO2021168353A2 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Artificial intelligence-based many-to-many base calling |
WO2021168014A1 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Knowledge distillation and gradient pruning-based compression of artificial intelligence-based base caller |
US11104937B2 (en) | 2017-03-15 | 2021-08-31 | The Broad Institute, Inc. | CRISPR effector system based diagnostics |
WO2021178467A1 (en) | 2020-03-03 | 2021-09-10 | Omniome, Inc. | Methods and compositions for sequencing double stranded nucleic acids |
EP3878974A1 (en) | 2015-07-06 | 2021-09-15 | Illumina Cambridge Limited | Sample preparation for nucleic acid amplification |
WO2021180733A1 (en) | 2020-03-09 | 2021-09-16 | Illumina, Inc. | Methods for sequencing polynucleotides |
US11136565B2 (en) | 2018-09-11 | 2021-10-05 | Singular Genomics Systems, Inc. | Modified archaeal family B polymerases |
WO2021202403A1 (en) | 2020-03-30 | 2021-10-07 | Illumina, Inc. | Methods and compositions for preparing nucleic acid libraries |
WO2021221500A1 (en) | 2020-04-27 | 2021-11-04 | Agendia N.V. | Treatment of her2 negative, mammaprint high risk 2 breast cancer. |
WO2021225886A1 (en) | 2020-05-05 | 2021-11-11 | Omniome, Inc. | Compositions and methods for modifying polymerase-nucleic acid complexes |
WO2021226285A1 (en) | 2020-05-05 | 2021-11-11 | Illumina, Inc. | Equalization-based image processing and spatial crosstalk attenuator |
US11174515B2 (en) | 2017-03-15 | 2021-11-16 | The Broad Institute, Inc. | CRISPR effector system based diagnostics |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
EP3910069A1 (en) | 2014-02-18 | 2021-11-17 | Illumina, Inc. | Methods and composition for dna profiling |
WO2021231477A2 (en) | 2020-05-12 | 2021-11-18 | Illumina, Inc. | Generating nucleic acids with modified bases using recombinant terminal deoxynucleotidyl transferase |
US11180794B2 (en) | 2018-05-31 | 2021-11-23 | Omniome, Inc. | Methods and compositions for capping nucleic acids |
US11181478B2 (en) | 2013-12-10 | 2021-11-23 | Illumina, Inc. | Biosensors for biological or chemical analysis and methods of manufacturing the same |
EP3913358A1 (en) | 2018-01-08 | 2021-11-24 | Illumina Inc | High-throughput sequencing with semiconductor-based detection |
EP3916108A1 (en) | 2016-11-17 | 2021-12-01 | Spatial Transcriptomics AB | Method for spatial tagging and analysing nucleic acids in a biological specimen |
US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
WO2021252800A1 (en) | 2020-06-11 | 2021-12-16 | Nautilus Biotechnology, Inc. | Methods and systems for computational decoding of biological, chemical, and physical entities |
WO2021252617A1 (en) | 2020-06-09 | 2021-12-16 | Illumina, Inc. | Methods for increasing yield of sequencing libraries |
WO2021259881A1 (en) | 2020-06-22 | 2021-12-30 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3' acetal blocking group |
WO2022006081A1 (en) | 2020-06-30 | 2022-01-06 | Illumina, Inc. | Catalytically controlled sequencing by synthesis to produce scarless dna |
WO2022006495A1 (en) | 2020-07-02 | 2022-01-06 | Illumina, Inc. | A method to calibrate nucleic acid library seeding efficiency in flowcells |
WO2022010965A1 (en) | 2020-07-08 | 2022-01-13 | Illumina, Inc. | Beads as transposome carriers |
WO2022023353A1 (en) | 2020-07-28 | 2022-02-03 | Illumina Cambridge Limited | Substituted coumarin dyes and uses as fluorescent labels |
WO2022031955A1 (en) | 2020-08-06 | 2022-02-10 | Illumina, Inc. | Preparation of rna and dna sequencing libraries using bead-linked transposomes |
WO2022040176A1 (en) | 2020-08-18 | 2022-02-24 | Illumina, Inc. | Sequence-specific targeted transposition and selection and sorting of nucleic acids |
US11268137B2 (en) | 2016-12-09 | 2022-03-08 | Boreal Genomics, Inc. | Linked ligation |
US11268091B2 (en) | 2018-12-13 | 2022-03-08 | Dna Script Sas | Direct oligonucleotide synthesis on cells and biomolecules |
US11268887B2 (en) | 2009-03-23 | 2022-03-08 | Bio-Rad Laboratories, Inc. | Manipulation of microfluidic droplets |
WO2022053610A1 (en) | 2020-09-11 | 2022-03-17 | Illumina Cambridge Limited | Methods of enriching a target sequence from a sequencing library using hairpin adaptors |
EP3974538A1 (en) | 2014-11-05 | 2022-03-30 | Illumina Cambridge Limited | Sequencing from multiple primers to increase data rate and density |
WO2022087150A2 (en) | 2020-10-21 | 2022-04-28 | Illumina, Inc. | Sequencing templates comprising multiple inserts and compositions and methods for improving sequencing throughput |
WO2022103499A1 (en) | 2020-11-11 | 2022-05-19 | Microsoft Technology Licensing, Llc | Spatial control of polynucleotide synthesis by strand capping |
EP4006150A1 (en) | 2015-09-09 | 2022-06-01 | QIAGEN GmbH | Polymerase enzyme |
US11352659B2 (en) | 2011-04-13 | 2022-06-07 | Spatial Transcriptomics Ab | Methods of detecting analytes |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
US11359238B2 (en) | 2020-03-06 | 2022-06-14 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
US11359221B2 (en) | 2019-02-12 | 2022-06-14 | Dna Script Sas | Efficient product cleavage in template-free enzymatic synthesis of polynucleotides |
WO2022129930A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Alkylpyridinium coumarin dyes and uses in sequencing applications |
WO2022129439A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Methods, systems and compositions for nucleic acid sequencing |
WO2022129437A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Long stokes shift chromenoquinoline dyes and uses in sequencing applications |
WO2022109269A3 (en) * | 2020-11-20 | 2022-06-30 | The General Hospital Corporation | Methods for dna methylation analysis |
WO2022140291A1 (en) | 2020-12-21 | 2022-06-30 | Singular Genomics Systems, Inc. | Systems and methods for multicolor imaging |
WO2022136402A1 (en) | 2020-12-22 | 2022-06-30 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing |
US11377655B2 (en) | 2019-07-16 | 2022-07-05 | Pacific Biosciences Of California, Inc. | Synthetic nucleic acids having non-natural structures |
US11390619B2 (en) | 2017-10-16 | 2022-07-19 | Illumina Cambridge Limited | Secondary amine-substituted coumarin compounds and their uses as fluorescent labels |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
WO2022155331A1 (en) | 2021-01-13 | 2022-07-21 | Pacific Biosciences Of California, Inc. | Surface structuring with colloidal assembly |
WO2022165188A1 (en) | 2021-01-29 | 2022-08-04 | Illumina, Inc. | Methods, compositions and kits to improve seeding efficiency of flow cells with polynucleotides |
US11408024B2 (en) | 2014-09-10 | 2022-08-09 | Molecular Loop Biosciences, Inc. | Methods for selectively suppressing non-target sequences |
WO2022169972A1 (en) | 2021-02-04 | 2022-08-11 | Illumina, Inc. | Long indexed-linked read generation on transposome bound beads |
WO2022174054A1 (en) | 2021-02-13 | 2022-08-18 | The General Hospital Corporation | Methods and compositions for in situ macromolecule detection and uses thereof |
WO2022197752A1 (en) | 2021-03-16 | 2022-09-22 | Illumina, Inc. | Tile location and/or cycle based weight set selection for base calling |
US11455487B1 (en) | 2021-10-26 | 2022-09-27 | Illumina Software, Inc. | Intensity extraction and crosstalk attenuation using interpolation and adaptation for base calling |
WO2022204032A1 (en) | 2021-03-22 | 2022-09-29 | Illumina Cambridge Limited | Methods for improving nucleic acid cluster clonality |
US11458469B2 (en) | 2016-10-14 | 2022-10-04 | Illumina, Inc. | Cartridge assembly |
WO2022212402A1 (en) | 2021-03-31 | 2022-10-06 | Illumina, Inc. | Methods of preparing directional tagmentation sequencing libraries using transposon-based technology with unique molecular identifiers for error correction |
WO2022212330A1 (en) | 2021-03-30 | 2022-10-06 | Illumina, Inc. | Improved methods of isothermal complementary dna and library preparation |
WO2022212280A1 (en) | 2021-03-29 | 2022-10-06 | Illumina, Inc. | Compositions and methods for assessing dna damage in a library and normalizing amplicon size bias |
WO2022213027A1 (en) | 2021-04-02 | 2022-10-06 | Illumina, Inc. | Machine-learning model for detecting a bubble within a nucleotide-sample slide for sequencing |
WO2022212269A1 (en) | 2021-03-29 | 2022-10-06 | Illumina, Inc. | Improved methods of library preparation |
CN115260262A (en) * | 2022-08-09 | 2022-11-01 | 深圳赛陆医疗科技有限公司 | Preparation method of cytosine azide |
US11486004B2 (en) | 2020-07-13 | 2022-11-01 | Singular Genomics Systems, Inc. | Methods of sequencing circular template polynucleotides |
US11486001B2 (en) | 2021-02-08 | 2022-11-01 | Singular Genomics Systems, Inc. | Methods and compositions for sequencing complementary polynucleotides |
EP4086357A1 (en) | 2015-08-28 | 2022-11-09 | Illumina, Inc. | Nucleic acid sequence analysis from single cells |
WO2022235163A1 (en) | 2021-05-07 | 2022-11-10 | Agendia N.V. | Endocrine treatment of hormone receptor positive breast cancer typed as having a low risk of recurrence |
WO2022233795A1 (en) | 2021-05-05 | 2022-11-10 | Illumina Cambridge Limited | Fluorescent dyes containing bis-boron fused heterocycles and uses in sequencing |
US11498078B2 (en) | 2019-12-23 | 2022-11-15 | Singular Genomics Systems, Inc. | Flow cell receiver and methods of use |
WO2022240766A1 (en) | 2021-05-10 | 2022-11-17 | Pacific Biosciences Of California, Inc. | Dna amplification buffer replenishment during rolling circle amplification |
WO2022240764A1 (en) | 2021-05-10 | 2022-11-17 | Pacific Biosciences Of California, Inc. | Single-molecule seeding and amplification on a surface |
WO2022243480A1 (en) | 2021-05-20 | 2022-11-24 | Illumina, Inc. | Compositions and methods for sequencing by synthesis |
US11512295B2 (en) | 2019-09-12 | 2022-11-29 | Singular Genomics Systems, Inc. | Modified thermoccocus polymerases |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11515010B2 (en) | 2021-04-15 | 2022-11-29 | Illumina, Inc. | Deep convolutional neural networks to predict variant pathogenicity using three-dimensional (3D) protein structures |
WO2022265994A1 (en) | 2021-06-15 | 2022-12-22 | Illumina, Inc. | Hydrogel-free surface functionalization for sequencing |
WO2023278608A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Self-learned base caller, trained using oligo sequences |
WO2023278927A1 (en) | 2021-06-29 | 2023-01-05 | Illumina Software, Inc. | Signal-to-noise-ratio metric for determining nucleotide-base calls and base-call quality |
WO2023278966A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Machine-learning model for generating confidence classifications for genomic coordinates |
WO2023278184A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Methods and systems to correct crosstalk in illumination emitted from reaction sites |
EP4119663A1 (en) | 2016-12-09 | 2023-01-18 | The Broad Institute, Inc. | Crispr effector system based diagnostics |
WO2023287617A1 (en) | 2021-07-13 | 2023-01-19 | Illumina, Inc. | Methods and systems for real time extraction of crosstalk in illumination emitted from reaction sites |
WO2023004323A1 (en) | 2021-07-23 | 2023-01-26 | Illumina Software, Inc. | Machine-learning model for recalibrating nucleotide-base calls |
WO2023004357A1 (en) | 2021-07-23 | 2023-01-26 | Illumina, Inc. | Methods for preparing substrate surface for dna sequencing |
WO2023003757A1 (en) | 2021-07-19 | 2023-01-26 | Illumina Software, Inc. | Intensity extraction with interpolation and adaptation for base calling |
WO2023009758A1 (en) | 2021-07-28 | 2023-02-02 | Illumina, Inc. | Quality score calibration of basecalling systems |
WO2023014741A1 (en) | 2021-08-03 | 2023-02-09 | Illumina Software, Inc. | Base calling using multiple base caller models |
US11578320B2 (en) | 2021-04-27 | 2023-02-14 | Singular Genomics Systems, Inc. | High density sequencing and multiplexed priming |
WO2023020728A1 (en) | 2021-08-14 | 2023-02-23 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2023023500A1 (en) | 2021-08-17 | 2023-02-23 | Illumina, Inc. | Methods and compositions for identifying methylated cytosines |
WO2023035108A1 (en) | 2021-09-07 | 2023-03-16 | 深圳华大智造科技股份有限公司 | Method for analyzing sequence of target polynucleotide |
WO2023035110A1 (en) | 2021-09-07 | 2023-03-16 | 深圳华大智造科技股份有限公司 | Method for analyzing sequence of target polynucleotide |
WO2023044229A1 (en) | 2021-09-17 | 2023-03-23 | Illumina, Inc. | Automatically identifying failure sources in nucleotide sequencing from base-call-error patterns |
WO2023049212A2 (en) | 2021-09-22 | 2023-03-30 | Illumina, Inc. | State-based base calling |
WO2023049558A1 (en) | 2021-09-21 | 2023-03-30 | Illumina, Inc. | A graph reference genome and base-calling approach using imputed haplotypes |
WO2023056328A2 (en) | 2021-09-30 | 2023-04-06 | Illumina, Inc. | Solid supports and methods for depleting and/or enriching library fragments prepared from biosamples |
WO2023052427A1 (en) | 2021-09-30 | 2023-04-06 | Illumina Cambridge Limited | Polynucleotide sequencing |
US11629380B2 (en) | 2021-03-12 | 2023-04-18 | Singular Genomics Systems, Inc. | Nanoarrays and methods of use thereof |
US11635427B2 (en) | 2010-09-30 | 2023-04-25 | Bio-Rad Laboratories, Inc. | Sandwich assays in droplets |
WO2023069927A1 (en) | 2021-10-20 | 2023-04-27 | Illumina, Inc. | Methods for capturing library dna for sequencing |
WO2023081485A1 (en) | 2021-11-08 | 2023-05-11 | Pacific Biosciences Of California, Inc. | Stepwise sequencing of a polynucleotide with a homogenous reaction mixture |
WO2023085932A1 (en) | 2021-11-10 | 2023-05-19 | Omnigen B.V. | Prediction of response following folfirinox treatment in cancer patients |
WO2023102354A1 (en) | 2021-12-02 | 2023-06-08 | Illumina Software, Inc. | Generating cluster-specific-signal corrections for determining nucleotide-base calls |
US11676685B2 (en) | 2019-03-21 | 2023-06-13 | Illumina, Inc. | Artificial intelligence-based quality scoring |
US11680950B2 (en) | 2019-02-20 | 2023-06-20 | Pacific Biosciences Of California, Inc. | Scanning apparatus and methods for detecting chemical and biological analytes |
WO2023122363A1 (en) | 2021-12-23 | 2023-06-29 | Illumina Software, Inc. | Dynamic graphical status summaries for nucelotide sequencing |
WO2023122362A1 (en) | 2021-12-23 | 2023-06-29 | Illumina Software, Inc. | Facilitating secure execution of external workflows for genomic sequencing diagnostics |
WO2023129764A1 (en) | 2021-12-29 | 2023-07-06 | Illumina Software, Inc. | Automatically switching variant analysis model versions for genomic analysis applications |
WO2023126457A1 (en) | 2021-12-29 | 2023-07-06 | Illumina Cambridge Ltd. | Methods of nucleic acid sequencing using surface-bound primers |
WO2023129896A1 (en) | 2021-12-28 | 2023-07-06 | Illumina Software, Inc. | Machine learning model for recalibrating nucleotide base calls corresponding to target variants |
US11697847B2 (en) | 2013-03-15 | 2023-07-11 | Illumina, Inc. | Super resolution imaging |
WO2023141154A1 (en) | 2022-01-20 | 2023-07-27 | Illumina Cambridge Limited | Methods of detecting methylcytosine and hydroxymethylcytosine by sequencing |
WO2023164492A1 (en) | 2022-02-25 | 2023-08-31 | Illumina, Inc. | Machine-learning models for detecting and adjusting values for nucleotide methylation levels |
WO2023164660A1 (en) | 2022-02-25 | 2023-08-31 | Illumina, Inc. | Calibration sequences for nucelotide sequencing |
US11747262B2 (en) | 2019-12-23 | 2023-09-05 | Singular Genomics Systems, Inc. | Flow cell carrier and methods of use |
WO2023183937A1 (en) | 2022-03-25 | 2023-09-28 | Illumina, Inc. | Sequence-to-sequence base calling |
WO2023186815A1 (en) | 2022-03-28 | 2023-10-05 | Illumina Cambridge Limited | Labeled avidin and methods for sequencing |
WO2023186819A1 (en) | 2022-03-29 | 2023-10-05 | Illumina Cambridge Limited | Chromenoquinoline dyes and uses in sequencing |
WO2023186982A1 (en) | 2022-03-31 | 2023-10-05 | Illumina, Inc. | Compositions and methods for improving sequencing signals |
WO2023192917A1 (en) | 2022-03-29 | 2023-10-05 | Nautilus Subsidiary, Inc. | Integrated arrays for single-analyte processes |
WO2023192900A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Singapore Pte. Ltd. | Nucleosides and nucleotides with 3' vinyl blocking group useful in sequencing by synthesis |
US11781185B2 (en) | 2020-10-30 | 2023-10-10 | Element Biosciences, Inc. | Methods and reagents for nucleic acid analysis |
WO2023196572A1 (en) | 2022-04-07 | 2023-10-12 | Illumina Singapore Pte. Ltd. | Altered cytidine deaminases and methods of use |
US11795505B2 (en) | 2022-03-10 | 2023-10-24 | Singular Genomics Systems, Inc. | Nucleic acid delivery scaffolds |
US11802307B2 (en) | 2021-09-03 | 2023-10-31 | Singular Genomics Systems, Inc. | Amplification oligonucleotides |
EP4269618A2 (en) | 2018-06-04 | 2023-11-01 | Illumina, Inc. | Methods of making high-throughput single-cell transcriptome libraries |
WO2023212601A1 (en) | 2022-04-26 | 2023-11-02 | Illumina, Inc. | Machine-learning models for selecting oligonucleotide probes for array technologies |
EP4276769A2 (en) | 2019-03-21 | 2023-11-15 | Illumina, Inc. | Training data generation for artificial intelligence-based sequencing |
WO2023220627A1 (en) | 2022-05-10 | 2023-11-16 | Illumina Software, Inc. | Adaptive neural network for nucelotide sequencing |
WO2023224487A1 (en) | 2022-05-19 | 2023-11-23 | Agendia N.V. | Prediction of response to immune therapy in breast cancer patients |
WO2023224488A1 (en) | 2022-05-19 | 2023-11-23 | Agendia N.V. | Dna repair signature and prediction of response following cancer therapy |
WO2023235353A2 (en) | 2022-06-03 | 2023-12-07 | Illumina, Inc. | Circulating rna biomarkers for preeclampsia |
WO2023232829A1 (en) | 2022-05-31 | 2023-12-07 | Illumina, Inc | Compositions and methods for nucleic acid sequencing |
US11840730B1 (en) | 2009-04-30 | 2023-12-12 | Molecular Loop Biosciences, Inc. | Methods and compositions for evaluating genetic markers |
WO2023239917A1 (en) | 2022-06-09 | 2023-12-14 | Illumina, Inc. | Dependence of base calling on flow cell tilt |
WO2023250504A1 (en) | 2022-06-24 | 2023-12-28 | Illumina Software, Inc. | Improving split-read alignment by intelligently identifying and scoring candidate split groups |
WO2024006769A1 (en) | 2022-06-27 | 2024-01-04 | Illumina Software, Inc. | Generating and implementing a structural variation graph genome |
WO2024006705A1 (en) | 2022-06-27 | 2024-01-04 | Illumina Software, Inc. | Improved human leukocyte antigen (hla) genotyping |
WO2024006779A1 (en) | 2022-06-27 | 2024-01-04 | Illumina, Inc. | Accelerators for a genotype imputation model |
WO2024003087A1 (en) | 2022-06-28 | 2024-01-04 | Illumina, Inc. | Fluorescent dyes containing fused tetracyclic bis-boron heterocycle and uses in sequencing |
US11866780B2 (en) | 2008-10-02 | 2024-01-09 | Illumina Cambridge Limited | Nucleic acid sample enrichment for sequencing applications |
US11866741B2 (en) | 2017-02-13 | 2024-01-09 | IsoPlexis Corporation | Polymerase enzyme from 9°N |
US11873480B2 (en) | 2014-10-17 | 2024-01-16 | Illumina Cambridge Limited | Contiguity preserving transposition |
WO2024015962A1 (en) | 2022-07-15 | 2024-01-18 | Pacific Biosciences Of California, Inc. | Blocked asymmetric hairpin adaptors |
US11884977B2 (en) | 2021-03-12 | 2024-01-30 | Singular Genomics Systems, Inc. | Nanoarrays and methods of use thereof |
US11884971B2 (en) | 2018-02-06 | 2024-01-30 | Pacific Biosciences Of California, Inc. | Compositions and techniques for nucleic acid primer extension |
WO2024026356A1 (en) | 2022-07-26 | 2024-02-01 | Illumina, Inc. | Rapid single-cell multiomics processing using an executable file |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
WO2024039516A1 (en) | 2022-08-19 | 2024-02-22 | Illumina, Inc. | Third dna base pair site-specific dna detection |
WO2024059852A1 (en) | 2022-09-16 | 2024-03-21 | Illumina, Inc. | Cluster segmentation and conditional base calling |
US11940413B2 (en) | 2007-02-05 | 2024-03-26 | IsoPlexis Corporation | Methods and devices for sequencing nucleic acids in smaller batches |
WO2024068971A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2024073519A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Machine-learning model for refining structural variant calls |
WO2024073043A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Methods of using cpg binding proteins in mapping modified cytosine nucleotides |
WO2024073516A1 (en) | 2022-09-29 | 2024-04-04 | Illumina, Inc. | A target-variant-reference panel for imputing target variants |
WO2024073047A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Cytidine deaminases and methods of use in mapping modified cytosine nucleotides |
WO2024069581A1 (en) | 2022-09-30 | 2024-04-04 | Illumina Singapore Pte. Ltd. | Helicase-cytidine deaminase complexes and methods of use |
WO2024068889A2 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Compositions and methods for reducing photo damage during sequencing |
WO2024077162A2 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for improving coronavirus sample surveillance |
WO2024077096A1 (en) | 2022-10-05 | 2024-04-11 | Illumina, Inc. | Integrating variant calls from multiple sequencing pipelines utilizing a machine learning architecture |
WO2024077152A1 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for depleting abundant small noncoding rna |
WO2024077202A2 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for improving environmental sample surveillance |
CN117886850A (en) * | 2024-03-14 | 2024-04-16 | 深圳赛陆医疗科技有限公司 | Preparation method of azide compound |
WO2024081649A1 (en) | 2022-10-11 | 2024-04-18 | Illumina, Inc. | Detecting and correcting methylation values from methylation sequencing assays |
RU2818762C2 (en) * | 2018-12-26 | 2024-05-06 | Иллюмина Кембридж Лимитед | Nucleosides and nucleotides with 3'-hydroxy blocking groups and their use in methods of sequencing polynucleotides |
US11981891B2 (en) | 2018-05-17 | 2024-05-14 | Illumina, Inc. | High-throughput single-cell sequencing with reduced amplification bias |
US11993801B2 (en) | 2020-07-21 | 2024-05-28 | Illumina Singapore Pte. Ltd. | Base-modified nucleotides as substrates for TdT-based enzymatic nucleic acid synthesis |
WO2024118791A1 (en) | 2022-11-30 | 2024-06-06 | Illumina, Inc. | Accurately predicting variants from methylation sequencing data |
WO2024118903A1 (en) | 2022-11-30 | 2024-06-06 | Illumina, Inc. | Chemoenzymatic correction of false positive uracil transformations |
WO2024123866A1 (en) | 2022-12-09 | 2024-06-13 | Illumina, Inc. | Nucleosides and nucleotides with 3´ blocking groups and cleavable linkers |
WO2024129672A1 (en) | 2022-12-12 | 2024-06-20 | The Broad Institute, Inc. | Trafficked rnas for assessment of cell-cell connectivity and neuroanatomy |
WO2024129969A1 (en) | 2022-12-14 | 2024-06-20 | Illumina, Inc. | Systems and methods for capture and enrichment of clustered beads on flow cell substrates |
WO2024130031A1 (en) | 2022-12-16 | 2024-06-20 | Illumina, Inc. | Boranes on solid supports |
WO2024137774A1 (en) | 2022-12-22 | 2024-06-27 | Illumina, Inc. | Palladium catalyst compositions and methods for sequencing by synthesis |
WO2024137886A1 (en) | 2022-12-21 | 2024-06-27 | Illumina, Inc. | Context-dependent base calling |
WO2024137765A1 (en) | 2022-12-22 | 2024-06-27 | Illumina, Inc. | Transition-metal catalyst compositions and methods for sequencing by synthesis |
WO2024145154A1 (en) | 2022-12-27 | 2024-07-04 | Illumina, Inc. | Methods of sequencing using 3´ allyl blocked nucleotides |
US12031179B2 (en) | 2020-10-30 | 2024-07-09 | Singular Genomics Systems, Inc. | Methods and compositions for reducing nucleotide impurities |
WO2024147904A1 (en) | 2023-01-06 | 2024-07-11 | Illumina, Inc. | Reducing uracils by polymerase |
US12038438B2 (en) | 2008-07-18 | 2024-07-16 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
WO2024167954A1 (en) | 2023-02-06 | 2024-08-15 | Illumina, Inc. | Determining and removing inter-cluster light interference |
WO2024173756A1 (en) | 2023-02-17 | 2024-08-22 | Illumina, Inc. | Cell-free dna signals as biomarkers of preeclampsia |
US12070744B2 (en) | 2021-04-22 | 2024-08-27 | Illumina, Inc. | Valve assemblies and related systems |
US12071665B2 (en) | 2020-10-22 | 2024-08-27 | Singular Genomics Systems, Inc. | Nucleic acid circularization and amplification on a surface |
US12091710B2 (en) | 2006-05-11 | 2024-09-17 | Bio-Rad Laboratories, Inc. | Systems and methods for handling microfluidic droplets |
Families Citing this family (179)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7057026B2 (en) * | 2001-12-04 | 2006-06-06 | Solexa Limited | Labelled nucleotides |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
GB0507835D0 (en) * | 2005-04-18 | 2005-05-25 | Solexa Ltd | Method and device for nucleic acid sequencing using a planar wave guide |
GB0517097D0 (en) | 2005-08-19 | 2005-09-28 | Solexa Ltd | Modified nucleosides and nucleotides and uses thereof |
WO2007053702A2 (en) | 2005-10-31 | 2007-05-10 | The Trustees Of Columbia University In The City Of New York | Synthesis of four color 3'-o-allyl modified photocleavable fluorescent nucleotides and related methods |
US8796432B2 (en) | 2005-10-31 | 2014-08-05 | The Trustees Of Columbia University In The City Of New York | Chemically cleavable 3'-o-allyl-DNTP-allyl-fluorophore fluorescent nucleotide analogues and related methods |
EP2363205A3 (en) | 2006-01-11 | 2014-06-04 | Raindance Technologies, Inc. | Microfluidic Devices And Methods Of Use In The Formation And Control Of Nanoreactors |
US9012390B2 (en) | 2006-08-07 | 2015-04-21 | Raindance Technologies, Inc. | Fluorocarbon emulsion stabilizing surfactants |
US20100035253A1 (en) * | 2008-03-19 | 2010-02-11 | Intelligent Bio-Systems, Inc. | Methods And Compositions For Incorporating Nucleotides |
US9017973B2 (en) | 2008-03-19 | 2015-04-28 | Intelligent Biosystems, Inc. | Methods and compositions for incorporating nucleotides |
US8039817B2 (en) | 2008-05-05 | 2011-10-18 | Illumina, Inc. | Compensator for multiple surface imaging |
WO2009137521A2 (en) * | 2008-05-07 | 2009-11-12 | Illumina, Inc. | Compositions and methods for providing substances to and from an array |
GB2473778B (en) | 2008-05-27 | 2013-04-10 | Trilink Biotechnologies | Chemically modified nucleoside 5'-triphosphates for thermally initiated amplification of nucleic acid |
US8486865B2 (en) * | 2008-11-03 | 2013-07-16 | The Regents Of The University Of California | Methods for detecting modification resistant nucleic acids |
US20100151473A1 (en) * | 2008-12-10 | 2010-06-17 | Yeakley Joanne M | Methods and compositions for hybridizing nucleic acids |
US20100261185A1 (en) | 2009-03-27 | 2010-10-14 | Life Technologies Corporation | Labeled enzyme compositions, methods and systems |
EP2427572B1 (en) * | 2009-05-01 | 2013-08-28 | Illumina, Inc. | Sequencing methods |
WO2010141390A2 (en) | 2009-06-05 | 2010-12-09 | Life Technologies Corporation | Nucleotide transient binding for sequencing methods |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
US8603741B2 (en) | 2010-02-18 | 2013-12-10 | Pacific Biosciences Of California, Inc. | Single molecule sequencing with two distinct chemistry steps |
US8951940B2 (en) | 2010-04-01 | 2015-02-10 | Illumina, Inc. | Solid-phase clonal amplification and related methods |
US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
US8483969B2 (en) | 2010-09-17 | 2013-07-09 | Illuminia, Inc. | Variation analysis for multiple templates on a solid support |
US8759038B2 (en) | 2010-09-29 | 2014-06-24 | Illumina Cambridge Limited | Compositions and methods for sequencing nucleic acids |
US8753816B2 (en) | 2010-10-26 | 2014-06-17 | Illumina, Inc. | Sequencing methods |
EP2632593B1 (en) | 2010-10-27 | 2021-09-29 | Illumina, Inc. | Flow cells for biological or chemical analysis |
WO2012061832A1 (en) | 2010-11-05 | 2012-05-10 | Illumina, Inc. | Linking sequence reads using paired code tags |
WO2012074855A2 (en) | 2010-11-22 | 2012-06-07 | The Regents Of The University Of California | Methods of identifying a cellular nascent rna transcript |
WO2013082164A1 (en) | 2011-11-28 | 2013-06-06 | Life Technologies Corporation | Enhanced ligation reactions |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
AU2012316218B2 (en) | 2011-09-26 | 2016-03-17 | Gen-Probe Incorporated | Algorithms for sequence determinations |
US9200274B2 (en) | 2011-12-09 | 2015-12-01 | Illumina, Inc. | Expanded radix for polymeric tags |
US9444880B2 (en) | 2012-04-11 | 2016-09-13 | Illumina, Inc. | Cloud computing environment for biological data |
CA2878291A1 (en) | 2012-07-03 | 2014-01-09 | Sloan Kettering Institute For Cancer Research | Quantitative assessment of human t-cell repertoire recovery after allogeneic hematopoietic stem cell transplantation |
US9150896B2 (en) * | 2012-09-06 | 2015-10-06 | Illumina, Inc. | Nucleotides and primers with removable blocking groups |
WO2014060483A1 (en) | 2012-10-17 | 2014-04-24 | Spatial Transcriptomics Ab | Methods and product for optimising localised or spatial detection of gene expression in a tissue sample |
US9116139B2 (en) | 2012-11-05 | 2015-08-25 | Illumina, Inc. | Sequence scheduling and sample distribution techniques |
US9146248B2 (en) | 2013-03-14 | 2015-09-29 | Intelligent Bio-Systems, Inc. | Apparatus and methods for purging flow cells in nucleic acid sequencing instruments |
EP2986597A4 (en) | 2013-04-19 | 2016-11-16 | Agency Science Tech & Res | Tunable fluorescence using cleavable linkers |
EP3013983B1 (en) | 2013-06-25 | 2023-02-15 | Prognosys Biosciences, Inc. | Spatially encoded biological assays using a microfluidic device |
US9352315B2 (en) | 2013-09-27 | 2016-05-31 | Taiwan Semiconductor Manufacturing Company, Ltd. | Method to produce chemical pattern in micro-fluidic structure |
CN103601778A (en) * | 2013-10-17 | 2014-02-26 | 上海交通大学 | Synthetic method of 7-denitrified-7-substituted guanosine |
EP2876166B1 (en) | 2013-11-20 | 2016-12-14 | Roche Diagnostics GmbH | New compound for sequencing by synthesis |
AU2015217139B2 (en) | 2014-02-13 | 2018-04-12 | Illumina, Inc. | Integrated consumer genomic services |
US10584366B2 (en) | 2014-12-03 | 2020-03-10 | IsoPlexis Corporation | Analysis and screening of cell secretion profiles |
WO2016182984A1 (en) * | 2015-05-08 | 2016-11-17 | Centrillion Technology Holdings Corporation | Disulfide-linked reversible terminators |
US10344336B2 (en) | 2015-06-09 | 2019-07-09 | Life Technologies Corporation | Methods, systems, compositions, kits, apparatus and computer-readable media for molecular tagging |
CN114989235A (en) | 2015-09-28 | 2022-09-02 | 哥伦比亚大学董事会 | Design and synthesis of nucleotides based on novel disulfide linkers for use as reversible terminators for DNA sequencing by synthesis |
US10577643B2 (en) | 2015-10-07 | 2020-03-03 | Illumina, Inc. | Off-target capture reduction in sequencing techniques |
KR102663563B1 (en) | 2015-11-09 | 2024-05-03 | 레디액션 엘티디. | Radiation shielding device and its application |
EP4372102A3 (en) | 2016-06-06 | 2024-08-14 | RedVault Biosciences, LP | Target reporter constructs and uses thereof |
WO2017218293A1 (en) | 2016-06-16 | 2017-12-21 | Richard Edward Watts | Oligonucleotide directed and recorded combinatorial synthesis of encoded probe molecules |
KR102416441B1 (en) | 2016-09-22 | 2022-07-04 | 일루미나, 인코포레이티드 | Detection of somatic copy number mutations |
EP3538891B1 (en) | 2016-11-11 | 2022-01-05 | Isoplexis Corporation | Compositions and methods for the simultaneous genomic, transcriptomic and proteomic analysis of single cells |
CN110226084A (en) | 2016-11-22 | 2019-09-10 | 伊索普莱克西斯公司 | For the systems, devices and methods of cell capture and its manufacturing method |
WO2018165207A1 (en) | 2017-03-06 | 2018-09-13 | Singular Genomic Systems, Inc. | Nucleic acid sequencing-by-synthesis (sbs) methods that combine sbs cycle steps |
US12018325B2 (en) | 2017-03-28 | 2024-06-25 | The Trustees Of Columbia University In The City Of New York | 3′-O-modified nucleotide analogues with different cleavable linkers for attaching fluorescent labels to the base for DNA sequencing by synthesis |
EP3619340A4 (en) | 2017-05-02 | 2021-01-20 | Haystack Sciences Corporation | Molecules for verifying oligonucleotide directed combinatorial synthesis and methods of making and using the same |
WO2018231818A1 (en) | 2017-06-16 | 2018-12-20 | Life Technologies Corporation | Control nucleic acids, and compositions, kits, and uses thereof |
JP6998404B2 (en) | 2017-08-01 | 2022-02-04 | 深▲セン▼恒特基因有限公司 | Method for enriching and determining the target nucleotide sequence |
US20190077726A1 (en) * | 2017-09-13 | 2019-03-14 | Singular Genomics Systems, Inc. | Methods of synthesizing labeled nucleosides |
JP2020536051A (en) | 2017-09-20 | 2020-12-10 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | Immunotherapeutic agents for patients whose tumors carry high passenger gene mutations |
JP7091372B2 (en) | 2017-11-06 | 2022-06-27 | イルミナ インコーポレイテッド | Nucleic acid indexing technology |
IL271214B1 (en) | 2017-11-16 | 2024-07-01 | Illumina Inc | Systems and methods for determining microsatellite instability |
JP7013490B2 (en) | 2017-11-30 | 2022-02-15 | イルミナ インコーポレイテッド | Validation methods and systems for sequence variant calls |
JP6868541B2 (en) * | 2017-12-05 | 2021-05-12 | イルミナ ケンブリッジ リミテッド | Modified nucleosides or modified nucleotides |
NL2021377B1 (en) | 2018-07-03 | 2020-01-08 | Illumina Inc | Interposer with first and second adhesive layers |
EP3836967A4 (en) | 2018-07-30 | 2022-06-15 | ReadCoor, LLC | Methods and systems for sample processing or analysis |
EP3844308A1 (en) | 2018-08-28 | 2021-07-07 | 10X Genomics, Inc. | Resolving spatial arrays |
US11519033B2 (en) | 2018-08-28 | 2022-12-06 | 10X Genomics, Inc. | Method for transposase-mediated spatial tagging and analyzing genomic DNA in a biological sample |
SG11202102029TA (en) | 2018-08-28 | 2021-03-30 | 10X Genomics Inc | Methods for generating spatially barcoded arrays |
EP3856753A4 (en) * | 2018-09-28 | 2022-11-16 | Centrillion Technology Holdings Corporation | Disulfide-linked reversible terminators |
WO2020073734A1 (en) | 2018-10-12 | 2020-04-16 | 深圳市真迈生物科技有限公司 | Biochip and manufacturing method therefor |
US20230028359A1 (en) | 2018-10-25 | 2023-01-26 | Singular Genomics Systems, Inc. | Nucleotide analogues |
NL2022043B1 (en) | 2018-11-21 | 2020-06-03 | Akershus Univ Hf | Tagmentation-Associated Multiplex PCR Enrichment Sequencing |
CN117680210A (en) | 2018-12-07 | 2024-03-12 | 元素生物科学公司 | Flow cell device, cartridge and system |
EP3894588A1 (en) | 2018-12-10 | 2021-10-20 | 10X Genomics, Inc. | Resolving spatial arrays using deconvolution |
CN113939230A (en) | 2019-01-02 | 2022-01-14 | 瑞迪艾森有限公司 | Patient head protection device |
US11649485B2 (en) | 2019-01-06 | 2023-05-16 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
US11926867B2 (en) | 2019-01-06 | 2024-03-12 | 10X Genomics, Inc. | Generating capture probes for spatial analysis |
WO2020146397A1 (en) * | 2019-01-08 | 2020-07-16 | Singular Genomics Systems, Inc. | Nucleotide cleavable linkers and uses thereof |
EP3921418A4 (en) | 2019-02-06 | 2023-02-08 | Singular Genomics Systems, Inc. | Compositions and methods for nucleic acid sequencing |
CN114174531A (en) | 2019-02-28 | 2022-03-11 | 10X基因组学有限公司 | Profiling of biological analytes with spatially barcoded oligonucleotide arrays |
CN114127309A (en) | 2019-03-15 | 2022-03-01 | 10X基因组学有限公司 | Method for single cell sequencing using spatial arrays |
EP3887542A1 (en) | 2019-03-22 | 2021-10-06 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
US11579217B2 (en) | 2019-04-12 | 2023-02-14 | Western Digital Technologies, Inc. | Devices and methods for frequency- and phase-based detection of magnetically-labeled molecules using spin torque oscillator (STO) sensors |
EP3941625A1 (en) | 2019-04-12 | 2022-01-26 | Western Digital Technologies Inc. | Nucleic acid sequencing by synthesis using magnetic sensor arrays |
US11738336B2 (en) | 2019-04-12 | 2023-08-29 | Western Digital Technologies, Inc. | Spin torque oscillator (STO) sensors used in nucleic acid sequencing arrays and detection schemes for nucleic acid sequencing |
US11327073B2 (en) | 2019-04-12 | 2022-05-10 | Western Digital Technologies, Inc. | Thermal sensor array for molecule detection and related detection schemes |
US11112468B2 (en) | 2019-04-12 | 2021-09-07 | Western Digital Technologies, Inc. | Magnetoresistive sensor array for molecule detection and related detection schemes |
US11609208B2 (en) | 2019-04-12 | 2023-03-21 | Western Digital Technologies, Inc. | Devices and methods for molecule detection based on thermal stabilities of magnetic nanoparticles |
WO2020243579A1 (en) | 2019-05-30 | 2020-12-03 | 10X Genomics, Inc. | Methods of detecting spatial heterogeneity of a biological sample |
US11208682B2 (en) | 2019-09-13 | 2021-12-28 | Western Digital Technologies, Inc. | Enhanced optical detection for nucleic acid sequencing using thermally-dependent fluorophore tags |
CN117036248A (en) | 2019-10-01 | 2023-11-10 | 10X基因组学有限公司 | System and method for identifying morphological patterns in tissue samples |
EP4055185A1 (en) | 2019-11-08 | 2022-09-14 | 10X Genomics, Inc. | Spatially-tagged analyte capture agents for analyte multiplexing |
WO2021092433A2 (en) | 2019-11-08 | 2021-05-14 | 10X Genomics, Inc. | Enhancing specificity of analyte binding |
US20210155982A1 (en) | 2019-11-21 | 2021-05-27 | 10X Genomics, Inc. | Pipeline for spatial analysis of analytes |
US11747329B2 (en) | 2019-11-22 | 2023-09-05 | Western Digital Technologies, Inc. | Magnetic gradient concentrator/reluctance detector for molecule detection |
WO2021133849A1 (en) | 2019-12-23 | 2021-07-01 | 10X Genomics, Inc. | Methods for spatial analysis using rna-templated ligation |
US11732299B2 (en) | 2020-01-21 | 2023-08-22 | 10X Genomics, Inc. | Spatial assays with perturbed cells |
US11702693B2 (en) | 2020-01-21 | 2023-07-18 | 10X Genomics, Inc. | Methods for printing cells and generating arrays of barcoded cells |
EP4097251A1 (en) | 2020-01-29 | 2022-12-07 | 10X Genomics, Inc. | Compositions and methods for analyte detection |
US12076701B2 (en) | 2020-01-31 | 2024-09-03 | 10X Genomics, Inc. | Capturing oligonucleotides in spatial transcriptomics |
US11898205B2 (en) | 2020-02-03 | 2024-02-13 | 10X Genomics, Inc. | Increasing capture efficiency of spatial assays |
US11732300B2 (en) | 2020-02-05 | 2023-08-22 | 10X Genomics, Inc. | Increasing efficiency of spatial analysis in a biological sample |
WO2021167986A1 (en) | 2020-02-17 | 2021-08-26 | 10X Genomics, Inc. | In situ analysis of chromatin interaction |
EP4106913A1 (en) | 2020-02-21 | 2022-12-28 | 10X Genomics, Inc. | Compositions, methods and systems for sample processing |
AU2021225020A1 (en) | 2020-02-21 | 2022-08-18 | 10X Genomics, Inc. | Methods and compositions for integrated in situ spatial assay |
US11891654B2 (en) | 2020-02-24 | 2024-02-06 | 10X Genomics, Inc. | Methods of making gene expression libraries |
EP4117818A2 (en) | 2020-03-10 | 2023-01-18 | Western Digital Technologies Inc. | Magnetic sensor arrays for nucleic acid sequencing and methods of making and using them |
CN113512083B (en) * | 2020-04-10 | 2023-05-23 | 深圳华大生命科学研究院 | Method for synthesizing nucleotide or nucleotide analogue |
EP4139485B1 (en) | 2020-04-22 | 2023-09-06 | 10X Genomics, Inc. | Methods for spatial analysis using targeted rna depletion |
US11739359B2 (en) | 2020-05-01 | 2023-08-29 | Microsoft Technology Licensing, Llc | Universal template strands for enzymatic polynucleotide synthesis |
WO2021224677A1 (en) | 2020-05-05 | 2021-11-11 | Akershus Universitetssykehus Hf | Compositions and methods for characterizing bowel cancer |
IL297920A (en) | 2020-05-08 | 2023-01-01 | Illumina Inc | Genome sequencing and detection techniques |
EP4153775B1 (en) | 2020-05-22 | 2024-07-24 | 10X Genomics, Inc. | Simultaneous spatio-temporal measurement of gene expression and cellular activity |
AU2021275906A1 (en) | 2020-05-22 | 2022-12-22 | 10X Genomics, Inc. | Spatial analysis to detect sequence variants |
WO2021242834A1 (en) | 2020-05-26 | 2021-12-02 | 10X Genomics, Inc. | Method for resetting an array |
US11702683B2 (en) | 2020-05-28 | 2023-07-18 | Microsoft Technology Licensing, Llc | De novo polynucleotide synthesis with substrate-bound polymerase |
US12031177B1 (en) | 2020-06-04 | 2024-07-09 | 10X Genomics, Inc. | Methods of enhancing spatial resolution of transcripts |
WO2021252499A1 (en) | 2020-06-08 | 2021-12-16 | 10X Genomics, Inc. | Methods of determining a surgical margin and methods of use thereof |
EP4165207B1 (en) | 2020-06-10 | 2024-09-25 | 10X Genomics, Inc. | Methods for determining a location of an analyte in a biological sample |
WO2021263111A1 (en) | 2020-06-25 | 2021-12-30 | 10X Genomics, Inc. | Spatial analysis of dna methylation |
CN111732623B (en) * | 2020-06-30 | 2022-01-18 | 中国科学院化学研究所 | Tri-isopropyl silaacetylene modified deoxycytidine phosphoramidite monomer and preparation method and application thereof |
US11981960B1 (en) | 2020-07-06 | 2024-05-14 | 10X Genomics, Inc. | Spatial analysis utilizing degradable hydrogels |
US11761038B1 (en) | 2020-07-06 | 2023-09-19 | 10X Genomics, Inc. | Methods for identifying a location of an RNA in a biological sample |
US11981958B1 (en) | 2020-08-20 | 2024-05-14 | 10X Genomics, Inc. | Methods for spatial analysis using DNA capture |
US20220067489A1 (en) | 2020-08-28 | 2022-03-03 | Illumina, Inc. | Detecting and Filtering Clusters Based on Artificial Intelligence-Predicted Base Calls |
WO2022056385A1 (en) | 2020-09-14 | 2022-03-17 | Singular Genomics Systems, Inc. | Methods and systems for multidimensional imaging |
US11926822B1 (en) | 2020-09-23 | 2024-03-12 | 10X Genomics, Inc. | Three-dimensional spatial analysis |
US12071667B2 (en) | 2020-11-04 | 2024-08-27 | 10X Genomics, Inc. | Sequence analysis using meta-stable nucleic acid molecules |
US11827935B1 (en) | 2020-11-19 | 2023-11-28 | 10X Genomics, Inc. | Methods for spatial analysis using rolling circle amplification and detection probes |
CN116157869A (en) | 2020-12-02 | 2023-05-23 | 伊鲁米纳软件公司 | Systems and methods for detecting genetic alterations |
US20220186300A1 (en) | 2020-12-11 | 2022-06-16 | 10X Genomics, Inc. | Methods and compositions for multimodal in situ analysis |
AU2021409136A1 (en) | 2020-12-21 | 2023-06-29 | 10X Genomics, Inc. | Methods, compositions, and systems for capturing probes and/or barcodes |
US12060603B2 (en) | 2021-01-19 | 2024-08-13 | 10X Genomics, Inc. | Methods for internally controlled in situ assays using padlock probes |
WO2022164809A1 (en) | 2021-01-26 | 2022-08-04 | 10X Genomics, Inc. | Nucleic acid analog probes for in situ analysis |
US20220282319A1 (en) | 2021-03-03 | 2022-09-08 | 10X Genomics, Inc. | Analyte detection in situ using nucleic acid origami |
KR20230165273A (en) | 2021-03-31 | 2023-12-05 | 일루미나 케임브리지 리미티드 | Nucleic acid library sequencing technology with adapter dimer detection |
CN115803816A (en) | 2021-03-31 | 2023-03-14 | 因美纳有限公司 | Artificial intelligence-based base detector with context awareness |
JP2024522025A (en) | 2021-04-29 | 2024-06-10 | イルミナ インコーポレイテッド | Amplification methods for nucleic acid characterization |
US20220372468A1 (en) | 2021-05-19 | 2022-11-24 | Microsoft Technology Licensing, Llc | Real-time detection of errors in oligonucleotide synthesis |
EP4347872A2 (en) | 2021-05-28 | 2024-04-10 | Illumina, Inc. | Oligo-modified nucleotide analogues for nucleic acid preparation |
WO2022256324A1 (en) | 2021-06-01 | 2022-12-08 | 10X Genomics, Inc. | Methods and compositions for analyte detection and probe resolution |
WO2022256422A1 (en) | 2021-06-02 | 2022-12-08 | 10X Genomics, Inc. | Sample analysis using asymmetric circularizable probes |
US20220403450A1 (en) | 2021-06-03 | 2022-12-22 | Illumina Software, Inc. | Systems and methods for sequencing nucleotides using two optical channels |
EP4347879A1 (en) | 2021-06-03 | 2024-04-10 | 10X Genomics, Inc. | Methods, compositions, kits, and systems for enhancing analyte capture for spatial analysis |
US20220411864A1 (en) | 2021-06-23 | 2022-12-29 | Illumina, Inc. | Compositions, methods, kits, cartridges, and systems for sequencing reagents |
US20230005253A1 (en) | 2021-07-01 | 2023-01-05 | Illumina, Inc. | Efficient artificial intelligence-based base calling of index sequences |
US20230026886A1 (en) | 2021-07-13 | 2023-01-26 | 10X Genomics, Inc. | Methods for preparing polymerized matrix with controllable thickness |
EP4381095A1 (en) | 2021-08-03 | 2024-06-12 | 10X Genomics, Inc. | Nucleic acid concatemers and methods for stabilizing and/or compacting the same |
CN117858958A (en) | 2021-08-16 | 2024-04-09 | 10X基因组学有限公司 | Probes comprising segmented barcode regions and methods of use |
EP4196605A1 (en) | 2021-09-01 | 2023-06-21 | 10X Genomics, Inc. | Methods, compositions, and kits for blocking a capture probe on a spatial array |
CN117580961A (en) | 2021-09-01 | 2024-02-20 | Illumina公司 | Amplitude modulation for accelerating base interpretation |
WO2023076687A1 (en) * | 2021-11-01 | 2023-05-04 | Twist Bioscience Corporation | Devices and methods for synthesis |
EP4305195A2 (en) | 2021-12-01 | 2024-01-17 | 10X Genomics, Inc. | Methods, compositions, and systems for improved in situ detection of analytes and spatial analysis |
WO2023107622A1 (en) | 2021-12-10 | 2023-06-15 | Illumina, Inc. | Parallel sample and index sequencing |
WO2023119164A1 (en) | 2021-12-21 | 2023-06-29 | Illumina Cambridge Limited | Wax-microsphere matrix compositions and methods of making and using the same |
WO2023129898A2 (en) | 2021-12-27 | 2023-07-06 | 10X Genomics, Inc. | Methods and compositions for rolling circle amplification |
US20230279475A1 (en) | 2022-01-21 | 2023-09-07 | 10X Genomics, Inc. | Multiple readout signals for analyzing a sample |
WO2023164570A1 (en) | 2022-02-23 | 2023-08-31 | Insitro, Inc. | Pooled optical screening and transcriptional measurements of cells comprising barcoded genetic perturbations |
WO2023175042A1 (en) | 2022-03-15 | 2023-09-21 | Illumina, Inc. | Parallel sample and index sequencing |
AU2023243205A1 (en) | 2022-04-01 | 2024-09-19 | 10X Genomics, Inc. | Compositions and methods for targeted masking of autofluorescence |
WO2023196526A1 (en) | 2022-04-06 | 2023-10-12 | 10X Genomics, Inc. | Methods for multiplex cell analysis |
US20240287583A1 (en) | 2022-04-08 | 2024-08-29 | Illumina, Inc. | Aptamer dynamic range compression and detection techniques |
US20230348967A1 (en) | 2022-04-29 | 2023-11-02 | Illumina Cambridge Limited | Methods and systems for encapsulating lyophilised microspheres |
WO2023215612A1 (en) | 2022-05-06 | 2023-11-09 | 10X Genomics, Inc. | Analysis of antigen and antigen receptor interactions |
WO2023225095A1 (en) | 2022-05-18 | 2023-11-23 | Illumina Cambridge Limited | Preparation of size-controlled nucleic acid fragments |
US20240035071A1 (en) | 2022-06-17 | 2024-02-01 | 10X Genomics, Inc. | Catalytic de-crosslinking of samples for in situ analysis |
WO2024036304A1 (en) | 2022-08-12 | 2024-02-15 | 10X Genomics, Inc. | Puma1 polymerases and uses thereof |
WO2024040060A1 (en) | 2022-08-16 | 2024-02-22 | 10X Genomics, Inc. | Ap50 polymerases and uses thereof |
US20240191297A1 (en) | 2022-10-14 | 2024-06-13 | 10X Genomics, Inc. | Methods, compositions, and systems for assessing biological sample quality |
WO2024098185A1 (en) | 2022-11-07 | 2024-05-16 | GeneSense Technology Inc., Shanghai (CN) | Nucleic acid sequencing using self-luminescence |
WO2024102736A1 (en) | 2022-11-08 | 2024-05-16 | 10X Genomics, Inc. | Immobilization methods and compositions for in situ detection |
WO2024107887A1 (en) | 2022-11-16 | 2024-05-23 | 10X Genomics, Inc. | Methods and compositions for assessing performance of in situ assays |
US20240218437A1 (en) | 2022-12-16 | 2024-07-04 | 10X Genomics, Inc. | Methods and compositions for assessing performance |
WO2024137860A1 (en) | 2022-12-21 | 2024-06-27 | 10X Genomics, Inc. | Methods for tethering ribonucleic acids in biological samples |
WO2024148300A1 (en) | 2023-01-06 | 2024-07-11 | 10X Genomics, Inc. | Methods and compositions for in situ analysis of variant sequences |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5302509A (en) | 1989-08-14 | 1994-04-12 | Beckman Instruments, Inc. | Method for sequencing polynucleotides |
WO2000006770A1 (en) | 1998-07-30 | 2000-02-10 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
WO2002029003A2 (en) | 2000-10-06 | 2002-04-11 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding dna and rna |
WO2003048387A2 (en) | 2001-12-04 | 2003-06-12 | Solexa Limited | Labelled nucleotides |
Family Cites Families (124)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US227131A (en) | 1880-05-04 | Heney o | ||
GB230037A (en) | 1924-02-27 | 1925-10-01 | Panhard & Levassor | Improvements in internal combustion engines provided with valve sleeves |
GB303924A (en) | 1927-10-13 | 1929-01-14 | Gregorio John Boonzaier | Improvements in or relating to carburettors for internal combustion engines |
US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
US5175269A (en) | 1984-01-30 | 1992-12-29 | Enzo Diagnostics, Inc. | Compound and detectable molecules having an oligo- or polynucleotide with modifiable reactive group |
US5118605A (en) | 1984-10-16 | 1992-06-02 | Chiron Corporation | Polynucleotide determination with selectable cleavage sites |
US4824775A (en) | 1985-01-03 | 1989-04-25 | Molecular Diagnostics, Inc. | Cells labeled with multiple Fluorophores bound to a nucleic acid carrier |
US4772691A (en) | 1985-06-05 | 1988-09-20 | The Medical College Of Wisconsin, Inc. | Chemically cleavable nucleotides |
US4863849A (en) | 1985-07-18 | 1989-09-05 | New York Medical College | Automatable process for sequencing nucleotide |
US4888274A (en) | 1985-09-18 | 1989-12-19 | Yale University | RecA nucleoprotein filament and methods |
US5047519A (en) | 1986-07-02 | 1991-09-10 | E. I. Du Pont De Nemours And Company | Alkynylamino-nucleotides |
US5242796A (en) | 1986-07-02 | 1993-09-07 | E. I. Du Pont De Nemours And Company | Method, system and reagents for DNA sequencing |
GB8810400D0 (en) | 1988-05-03 | 1988-06-08 | Southern E | Analysing polynucleotide sequences |
SE8801070D0 (en) | 1988-03-23 | 1988-03-23 | Pharmacia Ab | METHOD FOR IMMOBILIZING A DNA SEQUENCE ON A SOLID SUPPORT |
US4971903A (en) | 1988-03-25 | 1990-11-20 | Edward Hyman | Pyrophosphate-based method and apparatus for sequencing nucleic acids |
US5174962A (en) | 1988-06-20 | 1992-12-29 | Genomyx, Inc. | Apparatus for determining DNA sequences by mass spectrometry |
GB8910880D0 (en) | 1989-05-11 | 1989-06-28 | Amersham Int Plc | Sequencing method |
US5547839A (en) | 1989-06-07 | 1996-08-20 | Affymax Technologies N.V. | Sequencing of surface immobilized polymers utilizing microflourescence detection |
US6346413B1 (en) | 1989-06-07 | 2002-02-12 | Affymetrix, Inc. | Polymer arrays |
EP0450060A1 (en) | 1989-10-26 | 1991-10-09 | Sri International | Dna sequencing |
AU2674092A (en) | 1991-09-09 | 1993-04-05 | Baylor College Of Medicine | Method and device for rapid dna or rna sequencing determination by a base addition sequencing scheme |
DE4141178A1 (en) | 1991-12-13 | 1993-06-17 | Europ Lab Molekularbiolog | New nucleic acid sequencing method - using one labelled nucleotide at one time in cycles comprising elongation, wash, label detection and removal of the label, then repeating |
GB9208733D0 (en) * | 1992-04-22 | 1992-06-10 | Medical Res Council | Dna sequencing method |
GB9210176D0 (en) | 1992-05-12 | 1992-06-24 | Cemu Bioteknik Ab | Chemical method |
US5436143A (en) | 1992-12-23 | 1995-07-25 | Hyman; Edward D. | Method for enzymatic synthesis of oligonucleotides |
US5516664A (en) | 1992-12-23 | 1996-05-14 | Hyman; Edward D. | Enzymatic synthesis of repeat regions of oligonucleotides |
US6074823A (en) | 1993-03-19 | 2000-06-13 | Sequenom, Inc. | DNA sequencing by mass spectrometry via exonuclease degradation |
FR2703052B1 (en) | 1993-03-26 | 1995-06-02 | Pasteur Institut | New method of nucleic acid sequencing. |
US5959089A (en) | 1993-07-19 | 1999-09-28 | Hannessian; Stephen | Amino-cyclodextrin syntheses |
GB9315847D0 (en) | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
US5547859A (en) | 1993-08-02 | 1996-08-20 | Goodman; Myron F. | Chain-terminating nucleotides for DNA sequencing methods |
WO1995014108A1 (en) | 1993-11-17 | 1995-05-26 | Amersham International Plc | Primer extension mass spectroscopy nucleic acid sequencing method |
US5763594A (en) | 1994-09-02 | 1998-06-09 | Andrew C. Hiatt | 3' protected nucleotides for enzyme catalyzed template-independent creation of phosphodiester bonds |
US5872244A (en) | 1994-09-02 | 1999-02-16 | Andrew C. Hiatt | 3' protected nucleotides for enzyme catalyzed template-independent creation of phosphodiester bonds |
US6232465B1 (en) | 1994-09-02 | 2001-05-15 | Andrew C. Hiatt | Compositions for enzyme catalyzed template-independent creation of phosphodiester bonds using protected nucleotides |
US5808045A (en) | 1994-09-02 | 1998-09-15 | Andrew C. Hiatt | Compositions for enzyme catalyzed template-independent creation of phosphodiester bonds using protected nucleotides |
US6214987B1 (en) | 1994-09-02 | 2001-04-10 | Andrew C. Hiatt | Compositions for enzyme catalyzed template-independent formation of phosphodiester bonds using protected nucleotides |
US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
US6013445A (en) | 1996-06-06 | 2000-01-11 | Lynx Therapeutics, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
EP0785941B1 (en) | 1994-10-14 | 2000-04-19 | Stratagene | Porphyrin labeling of polynucleotides |
US5681940A (en) | 1994-11-02 | 1997-10-28 | Icn Pharmaceuticals | Sugar modified nucleosides and oligonucleotides |
DE4438918A1 (en) | 1994-11-04 | 1996-05-09 | Hoechst Ag | Modified oligonucleotides, their preparation and their use |
SE9500342D0 (en) | 1995-01-31 | 1995-01-31 | Marek Kwiatkowski | Novel chain terminators, the use thereof for nucleic acid sequencing and synthesis and a method of their preparation |
WO1996027025A1 (en) | 1995-02-27 | 1996-09-06 | Ely Michael Rabani | Device, compounds, algorithms, and methods of molecular characterization and manipulation with molecular parallelism |
EP0745686A1 (en) | 1995-06-01 | 1996-12-04 | Roche Diagnostics GmbH | The use of DNA polymerase 3'-intrinsic editing activity |
US5728528A (en) | 1995-09-20 | 1998-03-17 | The Regents Of The University Of California | Universal spacer/energy transfer dyes |
US6613508B1 (en) | 1996-01-23 | 2003-09-02 | Qiagen Genomics, Inc. | Methods and compositions for analyzing nucleic acid molecules utilizing sizing techniques |
US6312893B1 (en) | 1996-01-23 | 2001-11-06 | Qiagen Genomics, Inc. | Methods and compositions for determining the sequence of nucleic acid molecules |
EP0992511B1 (en) | 1996-01-23 | 2009-03-11 | Operon Biotechnologies, Inc. | Methods and compositions for determining the sequence of nucleic acid molecules |
US5821356A (en) | 1996-08-12 | 1998-10-13 | The Perkin Elmer Corporation | Propargylethoxyamino nucleotides |
US5885775A (en) | 1996-10-04 | 1999-03-23 | Perseptive Biosystems, Inc. | Methods for determining sequences information in polynucleotides using mass spectrometry |
JP2001508657A (en) | 1997-01-08 | 2001-07-03 | プロリゴ・エルエルシー | Oligonucleotide bioconjugation |
US6046005A (en) | 1997-01-15 | 2000-04-04 | Incyte Pharmaceuticals, Inc. | Nucleic acid sequencing with solid phase capturable terminators comprising a cleavable linking group |
WO1998033939A1 (en) | 1997-01-31 | 1998-08-06 | Hitachi, Ltd. | Method for determining nucleic acid base sequence and apparatus therefor |
JP3489991B2 (en) | 1997-07-07 | 2004-01-26 | 理化学研究所 | 3'-deoxyribonucleotide derivative |
EP1017848B2 (en) | 1997-07-28 | 2012-02-22 | Gen-Probe Incorporated | Nucleic acid sequence analysis |
US6008379A (en) | 1997-10-01 | 1999-12-28 | The Perkin-Elmer Corporation | Aromatic-substituted xanthene dyes |
US6485944B1 (en) | 1997-10-10 | 2002-11-26 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
WO1999019341A1 (en) | 1997-10-10 | 1999-04-22 | President & Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
US6511803B1 (en) | 1997-10-10 | 2003-01-28 | President And Fellows Of Harvard College | Replica amplification of nucleic acid arrays |
GB9815163D0 (en) | 1998-07-13 | 1998-09-09 | Brax Genomics Ltd | Compounds |
AU3199699A (en) | 1998-03-23 | 1999-10-18 | Invitrogen Corporation | Modified nucleotides and methods useful for nucleic acid sequencing |
US6780591B2 (en) | 1998-05-01 | 2004-08-24 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
JP3813818B2 (en) | 1998-05-01 | 2006-08-23 | アリゾナ ボード オブ リージェンツ | Method for determining the nucleotide sequence of oligonucleotides and DNA molecules |
US6096875A (en) | 1998-05-29 | 2000-08-01 | The Perlein-Elmer Corporation | Nucleotide compounds including a rigid linker |
US6218530B1 (en) | 1998-06-02 | 2001-04-17 | Ambergen Inc. | Compounds and methods for detecting biomolecules |
US6287821B1 (en) | 1998-06-11 | 2001-09-11 | Orchid Biosciences, Inc. | Nucleotide analogues with 3'-pro-fluorescent fluorophores in nucleic acid sequence analysis |
US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
US6218118B1 (en) | 1998-07-09 | 2001-04-17 | Agilent Technologies, Inc. | Method and mixture reagents for analyzing the nucleotide sequence of nucleic acids by mass spectrometry |
GB0002310D0 (en) | 2000-02-01 | 2000-03-22 | Solexa Ltd | Polynucleotide sequencing |
US6787308B2 (en) | 1998-07-30 | 2004-09-07 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
DE19844931C1 (en) | 1998-09-30 | 2000-06-15 | Stefan Seeger | Procedures for DNA or RNA sequencing |
US6221592B1 (en) | 1998-10-20 | 2001-04-24 | Wisconsin Alumi Research Foundation | Computer-based methods and systems for sequencing of individual nucleic acid molecules |
US6451525B1 (en) | 1998-12-03 | 2002-09-17 | Pe Corporation (Ny) | Parallel sequencing method |
WO2000036151A1 (en) | 1998-12-14 | 2000-06-22 | Li-Cor, Inc. | A heterogeneous assay for pyrophosphate detection |
US6380378B1 (en) | 1998-12-24 | 2002-04-30 | Toagosei Company, Ltd. | Nucleotide compound, nucleotide block oligonucleotide, and method for producing them |
US6087112A (en) | 1998-12-30 | 2000-07-11 | Oligos Etc. Inc. | Arrays with modified oligonucleotide and polynucleotide compositions |
ATE508200T1 (en) | 1999-02-23 | 2011-05-15 | Caliper Life Sciences Inc | SEQUENCING THROUGH INCORPORATION |
ES2310514T3 (en) | 1999-03-10 | 2009-01-16 | Asm Scientific, Inc. | A METHOD FOR DIRECT SEQUENCING OF NUCLEIC ACID. |
US7037654B2 (en) | 1999-04-30 | 2006-05-02 | Aclara Biosciences, Inc. | Methods and compositions for enhancing detection in determinations employing cleavable electrophoretic tag reagents |
US7056661B2 (en) | 1999-05-19 | 2006-06-06 | Cornell Research Foundation, Inc. | Method for sequencing nucleic acid molecules |
US6818395B1 (en) | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
US6242193B1 (en) | 1999-07-30 | 2001-06-05 | Hitachi, Ltd. | Apparatus for determining base sequence of nucleic acid |
US6982146B1 (en) | 1999-08-30 | 2006-01-03 | The United States Of America As Represented By The Department Of Health And Human Services | High speed parallel molecular nucleic acid sequencing |
WO2001016375A2 (en) | 1999-08-30 | 2001-03-08 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | High speed parallel molecular nucleic acid sequencing |
EP1218543A2 (en) | 1999-09-29 | 2002-07-03 | Solexa Ltd. | Polynucleotide sequencing |
US6309836B1 (en) | 1999-10-05 | 2001-10-30 | Marek Kwiatkowski | Compounds for protecting hydroxyls and methods for their use |
CA2388528A1 (en) | 1999-11-04 | 2001-05-10 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
AU3015801A (en) | 1999-12-23 | 2001-07-09 | Axaron Bioscience Ag | Method for carrying out the parallel sequencing of a nucleic acid mixture on a surface |
GB0002389D0 (en) | 2000-02-02 | 2000-03-22 | Solexa Ltd | Molecular arrays |
JP2003523978A (en) | 2000-02-18 | 2003-08-12 | シャイアー・バイオケム・インコーポレイテッド | Methods for treating or preventing FLAVIVIRUS infection using nucleoside analogs |
JP4721606B2 (en) | 2000-03-30 | 2011-07-13 | トヨタ自動車株式会社 | Method for determining the base sequence of a single nucleic acid molecule |
GB0013276D0 (en) | 2000-06-01 | 2000-07-26 | Amersham Pharm Biotech Uk Ltd | Nucleotide analogues |
GB0016473D0 (en) | 2000-07-05 | 2000-08-23 | Amersham Pharm Biotech Uk Ltd | Sequencing method |
DE10041539A1 (en) * | 2000-08-24 | 2002-03-07 | Febit Ferrarius Biotech Gmbh | New amidite derivatives for the synthesis of polymers on surfaces |
EP1322785A4 (en) | 2000-09-11 | 2005-11-09 | Univ Columbia | Combinatorial fluorescence energy transfer tags and uses thereof |
US20020155476A1 (en) | 2000-10-20 | 2002-10-24 | Nader Pourmand | Transient electrical signal based methods and devices for characterizing molecular interaction and/or motion in a sample |
JP2004523243A (en) | 2001-03-12 | 2004-08-05 | カリフォルニア インスティチュート オブ テクノロジー | Method and apparatus for analyzing polynucleotide sequences by asynchronous base extension |
US20030027140A1 (en) | 2001-03-30 | 2003-02-06 | Jingyue Ju | High-fidelity DNA sequencing using solid phase capturable dideoxynucleotides and mass spectrometry |
DE10120798B4 (en) | 2001-04-27 | 2005-12-29 | Genovoxx Gmbh | Method for determining gene expression |
DE10120797B4 (en) | 2001-04-27 | 2005-12-22 | Genovoxx Gmbh | Method for analyzing nucleic acid chains |
US6613523B2 (en) | 2001-06-29 | 2003-09-02 | Agilent Technologies, Inc. | Method of DNA sequencing using cleavable tags |
US7057031B2 (en) | 2001-07-13 | 2006-06-06 | Ambergen, Inc. | Nucleotide compositions comprising photocleavable markers and methods of preparation thereof |
AU2002337030A1 (en) | 2001-08-29 | 2003-03-18 | Genovoxx Gmbh | Method for analyzing nucleic acid sequences and gene expression |
GB0128526D0 (en) | 2001-11-29 | 2002-01-23 | Amersham Pharm Biotech Uk Ltd | Nucleotide analogues |
GB0129012D0 (en) | 2001-12-04 | 2002-01-23 | Solexa Ltd | Labelled nucleotides |
WO2003066812A2 (en) | 2002-02-05 | 2003-08-14 | Baylor College Of Medecine | Substituted 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene compounds for 8-color dna sequencing |
DE60301622T2 (en) | 2002-04-04 | 2006-06-14 | Biotage Ab Uppsala | PRIMER EXTENSION BASED PROCESS USING NUCLEOTIDES MARKED OVER COLD LINKERS |
US20040014096A1 (en) | 2002-04-12 | 2004-01-22 | Stratagene | Dual-labeled nucleotides |
US7074597B2 (en) | 2002-07-12 | 2006-07-11 | The Trustees Of Columbia University In The City Of New York | Multiplex genotyping using solid phase capturable dideoxynucleotides and mass spectrometry |
US7414116B2 (en) | 2002-08-23 | 2008-08-19 | Illumina Cambridge Limited | Labelled nucleotides |
EP3002289B1 (en) * | 2002-08-23 | 2018-02-28 | Illumina Cambridge Limited | Modified nucleotides for polynucleotide sequencing |
EP2119722B1 (en) | 2002-08-23 | 2016-10-26 | Illumina Cambridge Limited | Labelled nucleotides |
GB0321306D0 (en) | 2003-09-11 | 2003-10-15 | Solexa Ltd | Modified polymerases for improved incorporation of nucleotide analogues |
US7622279B2 (en) | 2004-03-03 | 2009-11-24 | The Trustees Of Columbia University In The City Of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
US7393533B1 (en) | 2004-11-08 | 2008-07-01 | La Jolla Institute For Allergy And Immunology | H3L envelope protein immunization methods and H3L envelope passive protection methods |
GB0517097D0 (en) | 2005-08-19 | 2005-09-28 | Solexa Ltd | Modified nucleosides and nucleotides and uses thereof |
US8481259B2 (en) | 2007-02-05 | 2013-07-09 | Intelligent Bio-Systems, Inc. | Methods and devices for sequencing nucleic acids in smaller batches |
EP2725107B1 (en) | 2007-10-19 | 2018-08-29 | The Trustees of Columbia University in the City of New York | DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified ddNTPs and nucleic acid comprising inosine with reversible terminators |
US20100035253A1 (en) | 2008-03-19 | 2010-02-11 | Intelligent Bio-Systems, Inc. | Methods And Compositions For Incorporating Nucleotides |
US9309569B2 (en) | 2010-08-26 | 2016-04-12 | Intelligent Bio-Systems, Inc. | Methods and compositions for sequencing nucleic acid using charge |
ES2641871T3 (en) | 2010-12-17 | 2017-11-14 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using modified nucleotides and nanopore detection |
US9624539B2 (en) | 2011-05-23 | 2017-04-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using Raman and infrared spectroscopy detection |
CN105377869B (en) | 2013-03-15 | 2018-07-10 | 伊鲁米纳剑桥有限公司 | The nucleosides or nucleotide of modification |
-
2003
- 2003-08-22 EP EP15184520.3A patent/EP3002289B1/en not_active Revoked
- 2003-08-22 US US10/525,401 patent/US7541444B2/en not_active Expired - Lifetime
- 2003-08-22 SI SI200332563T patent/SI3002289T1/en unknown
- 2003-08-22 ES ES12180077.5T patent/ES2550513T3/en not_active Expired - Lifetime
- 2003-08-22 EP EP19164666.0A patent/EP3587433B1/en not_active Revoked
- 2003-08-22 GB GB0405884A patent/GB2395954A/en not_active Withdrawn
- 2003-08-22 EP EP03792519A patent/EP1530578B1/en not_active Expired - Lifetime
- 2003-08-22 SI SI200332612T patent/SI3363809T1/en unknown
- 2003-08-22 EP EP20168283.8A patent/EP3795577A1/en active Pending
- 2003-08-22 SI SI200332613T patent/SI3587433T1/en unknown
- 2003-08-22 EP EP12180077.5A patent/EP2607369B1/en not_active Expired - Lifetime
- 2003-08-22 AU AU2003259350A patent/AU2003259350A1/en not_active Abandoned
- 2003-08-22 DK DK18157128.2T patent/DK3363809T3/en active
- 2003-08-22 EP EP18157128.2A patent/EP3363809B1/en not_active Revoked
- 2003-08-22 ES ES03792519T patent/ES2407681T3/en not_active Expired - Lifetime
- 2003-08-22 DK DK19164666.0T patent/DK3587433T3/en active
- 2003-08-22 DK DK15184520.3T patent/DK3002289T3/en active
- 2003-08-22 JP JP2005501219A patent/JP2006509040A/en active Pending
- 2003-08-22 WO PCT/GB2003/003686 patent/WO2004018497A2/en active Application Filing
-
2009
- 2009-06-01 US US12/455,397 patent/US7771973B2/en not_active Expired - Lifetime
-
2010
- 2010-07-20 US US12/804,352 patent/US8071739B2/en not_active Expired - Fee Related
- 2010-11-12 JP JP2010254204A patent/JP2011088898A/en active Pending
-
2011
- 2011-10-25 US US13/281,275 patent/US8597881B2/en not_active Expired - Lifetime
-
2013
- 2013-03-08 US US13/791,575 patent/US9121060B2/en not_active Expired - Fee Related
- 2013-07-19 JP JP2013150717A patent/JP5748805B2/en not_active Expired - Lifetime
-
2015
- 2015-08-07 US US14/821,548 patent/US9388464B2/en not_active Expired - Fee Related
-
2016
- 2016-06-10 US US15/179,813 patent/US10513731B2/en not_active Expired - Lifetime
-
2018
- 2018-04-04 CY CY20181100380T patent/CY1120186T1/en unknown
-
2019
- 2019-07-26 US US16/523,810 patent/US20200017908A1/en not_active Abandoned
-
2020
- 2020-05-18 US US16/877,442 patent/US20200399692A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5302509A (en) | 1989-08-14 | 1994-04-12 | Beckman Instruments, Inc. | Method for sequencing polynucleotides |
WO2000006770A1 (en) | 1998-07-30 | 2000-02-10 | Solexa Ltd. | Arrayed biomolecules and their use in sequencing |
WO2002029003A2 (en) | 2000-10-06 | 2002-04-11 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding dna and rna |
WO2003048387A2 (en) | 2001-12-04 | 2003-06-12 | Solexa Limited | Labelled nucleotides |
Non-Patent Citations (25)
Title |
---|
ACIDS RESEARCH, vol. 30, 2002, pages 605 - 613 |
ANSORGE ET AL., NUCL. ACIDS RES., vol. 15, no. 11, 1987, pages 4593 - 4602 |
BURGESS ET AL., J. ORG. CHEM., vol. 62, pages 5165,5168 |
CONNELL ET AL., BIOTECHNIQUES, vol. 5, no. 4, 1987, pages 342 - 384 |
EMPODOCLES ET AL., NATURE, vol. 399, 1999, pages 126 - 130 |
FODOR ET AL., TRENDS BIOTECH., vol. 12, 1994, pages 19 - 26 |
GREENE; WUTS: "Protective Groups in Organic Synthesis", JOHN WILEY & SONS |
GUILLIER ET AL., CHEM. REV., vol. 100, 2000, pages 2092 - 2157 |
J. AMER. CHEM. SOC., vol. 123, 2001, pages 8101 - 8108 |
KAMAL ET AL., TET. LET, vol. 40, 1999, pages 371 - 372 |
LACOSTE ET AL., PROC. NATL. ACAD. SCI USA, vol. 97, no. 17, 2000, pages 9461 - 9466 |
LEE ET AL., J. ORG. CHEM., vol. 64, 1999, pages 3454 - 3460 |
METZKER ET AL., NUCLEIC ACIDS RESEARCH, vol. 22, no. 20, 1994, pages 4259 - 4267 |
MOYER ET AL., LASER FOCUS WORLD, vol. 29, 1993, pages 10 |
NUCLEIC ACIDS RESEARCH, vol. 27, 1999, pages 2454 - 2553 |
PROBER ET AL., SCIENCE, vol. 238, 1987, pages 336 - 341 |
PROC. NATL. ACAD. SCI. USA, vol. 93, 1996, pages 5281 - 5285 |
REICHERT ET AL., ANAL. CHEM., vol. 72, 2000, pages 6025 - 6029 |
SCHEIT: "Nucleotide Analogs", 1980, JOHN WILEY & SON |
SMITH ET AL., NATURE, vol. 321, 1986, pages 674 |
STIMPSON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 92, 1995, pages 6379 - 6383 |
TET. LET., vol. 46, 2000, pages 8867 - 8871 |
UHLMAN ET AL., CHEMICAL REVIEWS, vol. 90, 1990, pages 543 - 584 |
WELCH ET AL., CHEM. EUR. J., vol. 5, no. 3, 1999, pages 951 - 960 |
ZHU ET AL., CYTOMETRY, vol. 28, 1997, pages 206 - 211 |
Cited By (1020)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10662472B2 (en) | 2000-10-06 | 2020-05-26 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10669582B2 (en) | 2000-10-06 | 2020-06-02 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9718852B2 (en) | 2000-10-06 | 2017-08-01 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10577652B2 (en) | 2000-10-06 | 2020-03-03 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10633700B2 (en) | 2000-10-06 | 2020-04-28 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10648028B2 (en) | 2000-10-06 | 2020-05-12 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10407458B2 (en) | 2000-10-06 | 2019-09-10 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US7345159B2 (en) | 2000-10-06 | 2008-03-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9725480B2 (en) | 2000-10-06 | 2017-08-08 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9719139B2 (en) | 2000-10-06 | 2017-08-01 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10407459B2 (en) | 2000-10-06 | 2019-09-10 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10570446B2 (en) | 2000-10-06 | 2020-02-25 | The Trustee Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9708358B2 (en) | 2000-10-06 | 2017-07-18 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10669577B2 (en) | 2000-10-06 | 2020-06-02 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10428380B2 (en) | 2000-10-06 | 2019-10-01 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US7635578B2 (en) | 2000-10-06 | 2009-12-22 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US9868985B2 (en) | 2000-10-06 | 2018-01-16 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10457984B2 (en) | 2000-10-06 | 2019-10-29 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10435742B2 (en) | 2000-10-06 | 2019-10-08 | The Trustees Of Columbia University In The City Of New York | Massive parallel method for decoding DNA and RNA |
US10519496B2 (en) | 2001-12-04 | 2019-12-31 | Illumina Cambridge Limited | Labelled nucleotides |
US10480025B2 (en) | 2001-12-04 | 2019-11-19 | Illumina Cambridge Limited | Labelled nucleotides |
US9605310B2 (en) | 2001-12-04 | 2017-03-28 | Illumina Cambridge Limited | Labelled nucleotides |
EP1530578B1 (en) | 2002-08-23 | 2013-03-13 | Illumina Cambridge Limited | Modified nucleotides for polynucleotide sequencing |
US10513731B2 (en) | 2002-08-23 | 2019-12-24 | Illumina Cambridge Limited | Modified nucleotides |
EP3363809B1 (en) | 2002-08-23 | 2020-04-08 | Illumina Cambridge Limited | Modified nucleotides for polynucleotide sequencing |
US10487102B2 (en) | 2002-08-23 | 2019-11-26 | Illumina Cambridge Limited | Labelled nucleotides |
EP3587433B1 (en) | 2002-08-23 | 2020-04-22 | Illumina Cambridge Limited | Modified nucleotides |
EP3438116B1 (en) | 2002-08-23 | 2021-02-17 | Illumina Cambridge Limited | Labelled nucleotides |
US11008359B2 (en) | 2002-08-23 | 2021-05-18 | Illumina Cambridge Limited | Labelled nucleotides |
US11187702B2 (en) | 2003-03-14 | 2021-11-30 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US10052605B2 (en) | 2003-03-31 | 2018-08-21 | Medical Research Council | Method of synthesis and testing of combinatorial libraries using microcapsules |
US9857303B2 (en) | 2003-03-31 | 2018-01-02 | Medical Research Council | Selection by compartmentalised screening |
US11028116B2 (en) | 2003-08-22 | 2021-06-08 | Illumina Cambridge Limited | Labelled nucleotides |
US10995111B2 (en) | 2003-08-22 | 2021-05-04 | Illumina Cambridge Limited | Labelled nucleotides |
US11028115B2 (en) | 2003-08-22 | 2021-06-08 | Illumina Cambridge Limited | Labelled nucleotides |
US8852910B2 (en) | 2003-09-11 | 2014-10-07 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
US11473067B2 (en) | 2003-09-11 | 2022-10-18 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
EP1664287B1 (en) * | 2003-09-11 | 2011-11-09 | Illumina Cambridge Limited | Modified b type dna polymerases for improved incorporation of nucleotide analogues |
US11136564B2 (en) | 2003-09-11 | 2021-10-05 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
US8460910B2 (en) | 2003-09-11 | 2013-06-11 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
US10017750B2 (en) | 2003-09-11 | 2018-07-10 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
US9447389B2 (en) | 2003-09-11 | 2016-09-20 | Illumina Cambridge Limited | Modified polymerases for improved incorporation of nucleotide analogues |
JP2007504817A (en) * | 2003-09-11 | 2007-03-08 | ソレックサ リミテッド | Modified polymerases for improved incorporation of nucleotide analogs |
WO2005044836A2 (en) | 2003-11-05 | 2005-05-19 | Genovoxx Gmbh | Macromolecular nucleotide compounds and methods for using the same |
US7622279B2 (en) | 2004-03-03 | 2009-11-24 | The Trustees Of Columbia University In The City Of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
JP2005255604A (en) * | 2004-03-11 | 2005-09-22 | Mitsui Chemicals Inc | Method for producing n-acetylcytidine |
US9925504B2 (en) | 2004-03-31 | 2018-03-27 | President And Fellows Of Harvard College | Compartmentalised combinatorial chemistry by microfluidic control |
US11821109B2 (en) | 2004-03-31 | 2023-11-21 | President And Fellows Of Harvard College | Compartmentalised combinatorial chemistry by microfluidic control |
US9839890B2 (en) | 2004-03-31 | 2017-12-12 | National Science Foundation | Compartmentalised combinatorial chemistry by microfluidic control |
US11786872B2 (en) | 2004-10-08 | 2023-10-17 | United Kingdom Research And Innovation | Vitro evolution in microfluidic systems |
US9029083B2 (en) | 2004-10-08 | 2015-05-12 | Medical Research Council | Vitro evolution in microfluidic systems |
EP2241637A1 (en) | 2005-02-01 | 2010-10-20 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
US10323277B2 (en) | 2005-02-01 | 2019-06-18 | Applied Biosystems, Llc | Reagents, methods, and libraries for bead-based sequencing |
EP2857523A1 (en) | 2005-02-01 | 2015-04-08 | Applied Biosystems, LLC | Method for identifying a sequence in a polynucleotide |
EP2003214A2 (en) | 2005-02-01 | 2008-12-17 | AB Advanced Genetic Analysis Corporation | Reagents, methods, and libraries for bead-based sequencing |
EP2230316A1 (en) | 2005-02-01 | 2010-09-22 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
EP2230315A1 (en) | 2005-02-01 | 2010-09-22 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
EP2233581A1 (en) | 2005-02-01 | 2010-09-29 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
EP2316977A1 (en) | 2005-02-01 | 2011-05-04 | AB Advanced Genetic Analysis Corporation | Reagents, methods and libraries for bead-based amflication |
EP2233582A1 (en) | 2005-02-01 | 2010-09-29 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
EP2233583A1 (en) | 2005-02-01 | 2010-09-29 | AB Advanced Genetic Analysis Corporation | Nucleic acid sequencing by performing successive cycles of duplex extension |
EP2236628A2 (en) | 2005-02-01 | 2010-10-06 | AB Advanced Genetic Analysis Corporation | Reagents, methods and libraries for bead-based sequencing |
EP2272983A1 (en) | 2005-02-01 | 2011-01-12 | AB Advanced Genetic Analysis Corporation | Reagents, methods and libraries for bead-based sequencing |
EP2239342A2 (en) | 2005-02-01 | 2010-10-13 | AB Advanced Genetic Analysis Corporation | Reagents, methods and libraries for bead-based sequencing |
US8623628B2 (en) | 2005-05-10 | 2014-01-07 | Illumina, Inc. | Polymerases |
US9273352B2 (en) | 2005-05-10 | 2016-03-01 | Illumina Cambridge Limited | Polymerases |
US10059928B2 (en) | 2005-05-10 | 2018-08-28 | Illumina Cambridge Limited | Polymerases |
US9944984B2 (en) | 2005-06-15 | 2018-04-17 | Complete Genomics, Inc. | High density DNA array |
EP2620510B1 (en) | 2005-06-15 | 2016-10-12 | Complete Genomics Inc. | Single molecule arrays for genetic and chemical analysis |
US10351909B2 (en) | 2005-06-15 | 2019-07-16 | Complete Genomics, Inc. | DNA sequencing from high density DNA arrays using asynchronous reactions |
EP1907583B1 (en) | 2005-06-15 | 2016-10-05 | Complete Genomics Inc. | Single molecule arrays for genetic and chemical analysis |
EP1907583B2 (en) † | 2005-06-15 | 2019-10-23 | Complete Genomics Inc. | Single molecule arrays for genetic and chemical analysis |
WO2007002204A2 (en) * | 2005-06-21 | 2007-01-04 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compostions |
WO2007002204A3 (en) * | 2005-06-21 | 2009-04-09 | Univ Columbia | Pyrosequencing methods and related compostions |
US9909177B2 (en) | 2005-06-21 | 2018-03-06 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compositions |
US9169510B2 (en) * | 2005-06-21 | 2015-10-27 | The Trustees Of Columbia University In The City Of New York | Pyrosequencing methods and related compositions |
US10793904B2 (en) | 2005-07-20 | 2020-10-06 | Illumina Cambridge Limited | Methods for sequencing a polynucleotide template |
US9765391B2 (en) | 2005-07-20 | 2017-09-19 | Illumina Cambridge Limited | Methods for sequencing a polynucleotide template |
US11542553B2 (en) | 2005-07-20 | 2023-01-03 | Illumina Cambridge Limited | Methods for sequencing a polynucleotide template |
JP2007056001A (en) * | 2005-07-27 | 2007-03-08 | Gunma Univ | New nucleic acid derivative and method for producing polynucleotide using the same |
US8859753B2 (en) | 2005-10-27 | 2014-10-14 | President And Fellows Of Harvard College | Methods and compositions for labeling nucleic acids |
US7910335B2 (en) | 2005-10-27 | 2011-03-22 | President And Fellows Of Harvard College | Methods and compositions for labeling nucleic acids |
US9790541B2 (en) | 2005-10-27 | 2017-10-17 | President And Fellows Of Harvard College | Methods and compositions for labeling nucleic acids |
EP2918686A1 (en) | 2005-11-25 | 2015-09-16 | Illumina Cambridge Limited | Preparation of nucleic acid templates for solid phase amplification |
US10676771B2 (en) | 2006-02-10 | 2020-06-09 | Life Technologies Corporation | Oligosaccharide modification and labeling of proteins |
US8785212B2 (en) | 2006-02-10 | 2014-07-22 | Life Technologies Corporation | Oligosaccharide modification and labeling of proteins |
US8114636B2 (en) | 2006-02-10 | 2012-02-14 | Life Technologies Corporation | Labeling and detection of nucleic acids |
US9645140B2 (en) | 2006-02-10 | 2017-05-09 | Life Technologies Corporation | Labeling and detection of post translationally modified proteins |
EP3722409A1 (en) | 2006-03-31 | 2020-10-14 | Illumina, Inc. | Systems and devices for sequence by synthesis analysis |
EP3373174A1 (en) | 2006-03-31 | 2018-09-12 | Illumina, Inc. | Systems and devices for sequence by synthesis analysis |
EP4105644A2 (en) | 2006-03-31 | 2022-12-21 | Illumina, Inc. | Systems and devices for sequence by synthesis analysis |
EP2963127A1 (en) | 2006-04-04 | 2016-01-06 | Keygene N.V. | High throughput detection of molecular markers based on restriction fragments |
US12091710B2 (en) | 2006-05-11 | 2024-09-17 | Bio-Rad Laboratories, Inc. | Systems and methods for handling microfluidic droplets |
US11351510B2 (en) | 2006-05-11 | 2022-06-07 | Bio-Rad Laboratories, Inc. | Microfluidic devices |
WO2007135368A2 (en) * | 2006-05-18 | 2007-11-29 | Solexa Limited | Dye compounds and the use of their labelled conjugates |
WO2007135368A3 (en) * | 2006-05-18 | 2008-03-06 | Solexa Ltd | Dye compounds and the use of their labelled conjugates |
US8178360B2 (en) | 2006-05-18 | 2012-05-15 | Illumina Cambridge Limited | Dye compounds and the use of their labelled conjugates |
USRE49362E1 (en) | 2006-05-18 | 2023-01-10 | Illumina Cambridge Limited | Dye compounds and the use of their labelled conjugates |
US9415368B2 (en) | 2006-06-23 | 2016-08-16 | Illumina, Inc. | Devices and systems for creation of DNA cluster arrays |
US8921073B2 (en) | 2006-06-23 | 2014-12-30 | Illumina, Inc. | Devices and systems for creation of DNA cluster arrays |
EP2182079A1 (en) | 2006-07-12 | 2010-05-05 | Keygene N.V. | High throughput physical mapping using AFLP |
EP2275576A1 (en) | 2006-07-12 | 2011-01-19 | Keygene N.V. | High throughput physical mapping using AFLP |
EP2821506A1 (en) | 2006-07-12 | 2015-01-07 | Keygene N.V. | Identification of clones by sequencing of pool-specific adapters |
WO2008037568A2 (en) * | 2006-09-04 | 2008-04-03 | Quiatech Ab | Reversible terminators for efficient sequencing by synthesis |
WO2008037568A3 (en) * | 2006-09-04 | 2008-10-02 | Quiatech Ab | Reversible terminators for efficient sequencing by synthesis |
US9051612B2 (en) | 2006-09-28 | 2015-06-09 | Illumina, Inc. | Compositions and methods for nucleotide sequencing |
EP3670672A1 (en) | 2006-10-06 | 2020-06-24 | Illumina Cambridge Limited | Method for sequencing a polynucleotide template |
US9139826B2 (en) | 2006-10-10 | 2015-09-22 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
US9340781B2 (en) | 2006-10-10 | 2016-05-17 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
US9587273B2 (en) | 2006-10-10 | 2017-03-07 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
US10538759B2 (en) | 2006-10-10 | 2020-01-21 | Illumina, Inc. | Compounds and method for representational selection of nucleic acids from complex mixtures using hybridization |
US8916350B2 (en) | 2006-10-10 | 2014-12-23 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
US8568979B2 (en) | 2006-10-10 | 2013-10-29 | Illumina, Inc. | Compositions and methods for representational selection of nucleic acids from complex mixtures using hybridization |
US11939631B2 (en) | 2006-12-01 | 2024-03-26 | The Trustees Of Columbia University In The City Of New York | Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators |
US11098353B2 (en) | 2006-12-01 | 2021-08-24 | The Trustees Of Columbia University In The City Of New York | Four-color DNA sequencing by synthesis using cleavable fluorescent nucleotide reversible terminators |
US7964352B2 (en) | 2006-12-05 | 2011-06-21 | Lasergen, Inc. | 3′-OH unblocked nucleotides and nucleosides, base modified with labels and photocleavable, terminating groups and methods for their use in DNA sequencing |
US8361727B2 (en) | 2006-12-05 | 2013-01-29 | Lasergen, Inc. | 3′OH-unblocked, nucleotides and nucleosides base modified with labels and photocleavable, terminating groups and methods for their use in DNA sequencing |
US7897737B2 (en) * | 2006-12-05 | 2011-03-01 | Lasergen, Inc. | 3′-OH unblocked, nucleotides and nucleosides, base modified with photocleavable, terminating groups and methods for their use in DNA sequencing |
US8198029B2 (en) | 2006-12-05 | 2012-06-12 | Lasergen, Inc | 3'-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing |
US8969535B2 (en) | 2006-12-05 | 2015-03-03 | Lasergen, Inc. | Photocleavable labeled nucleotides and nucleosides and methods for their use in DNA sequencing |
US7893227B2 (en) * | 2006-12-05 | 2011-02-22 | Lasergen, Inc. | 3′-OH unblocked nucleotides and nucleosides base modified with non-cleavable, terminating groups and methods for their use in DNA sequencing |
US11940413B2 (en) | 2007-02-05 | 2024-03-26 | IsoPlexis Corporation | Methods and devices for sequencing nucleic acids in smaller batches |
US9017623B2 (en) | 2007-02-06 | 2015-04-28 | Raindance Technologies, Inc. | Manipulation of fluids and reactions in microfluidic systems |
US10603662B2 (en) | 2007-02-06 | 2020-03-31 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
US11819849B2 (en) | 2007-02-06 | 2023-11-21 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
WO2008101024A3 (en) * | 2007-02-13 | 2008-10-09 | Invitrogen Corp | Labeling and detection of nucleic acids |
US9068699B2 (en) | 2007-04-19 | 2015-06-30 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US10357772B2 (en) | 2007-04-19 | 2019-07-23 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US10960397B2 (en) | 2007-04-19 | 2021-03-30 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US11224876B2 (en) | 2007-04-19 | 2022-01-18 | Brandeis University | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US11618024B2 (en) | 2007-04-19 | 2023-04-04 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US10675626B2 (en) | 2007-04-19 | 2020-06-09 | President And Fellows Of Harvard College | Manipulation of fluids, fluid components and reactions in microfluidic systems |
US10260094B2 (en) | 2007-10-19 | 2019-04-16 | The Trustees Of Columbia University In The City Of New York | DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified nucleotide terminators |
US10144961B2 (en) | 2007-10-19 | 2018-12-04 | The Trustees Of Columbia University In The City Of New York | Synthesis of cleavable fluorescent nucleotides as reversible terminators for DNA sequencing by synthesis |
US9670539B2 (en) | 2007-10-19 | 2017-06-06 | The Trustees Of Columbia University In The City Of New York | Synthesis of cleavable fluorescent nucleotides as reversible terminators for DNA sequencing by synthesis |
US11208691B2 (en) | 2007-10-19 | 2021-12-28 | The Trustees Of Columbia University In The City Of New York | Synthesis of cleavable fluorescent nucleotides as reversible terminators for DNA sequencing by synthesis |
US11242561B2 (en) | 2007-10-19 | 2022-02-08 | The Trustees Of Columbia University In The City Of New York | DNA sequencing with non-fluorescent nucleotide reversible terminators and cleavable label modified nucleotide terminators |
US9932297B2 (en) | 2007-11-21 | 2018-04-03 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
US9227943B2 (en) | 2007-11-21 | 2016-01-05 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
US8133515B2 (en) | 2007-11-21 | 2012-03-13 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
US8940859B2 (en) | 2007-11-21 | 2015-01-27 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
US9725405B2 (en) | 2007-11-21 | 2017-08-08 | University Of Georgia Research Foundation, Inc. | Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds |
US11214832B2 (en) | 2008-01-28 | 2022-01-04 | Complete Genomics, Inc. | Methods and compositions for efficient base calling in sequencing reactions |
US11098356B2 (en) | 2008-01-28 | 2021-08-24 | Complete Genomics, Inc. | Methods and compositions for nucleic acid sequencing |
WO2009116863A2 (en) | 2008-03-17 | 2009-09-24 | Expressive Research B.V. | Expression-linked gene discovery |
US9644198B2 (en) | 2008-04-30 | 2017-05-09 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
US8911948B2 (en) | 2008-04-30 | 2014-12-16 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
US9434988B2 (en) | 2008-04-30 | 2016-09-06 | Integrated Dna Technologies, Inc. | RNase H-based assays utilizing modified RNA monomers |
EP2644710A1 (en) * | 2008-04-30 | 2013-10-02 | Integrated Dna Technologies, Inc. | RNase-H-based assays utilizing modified RNA monomers |
US10138510B2 (en) | 2008-05-16 | 2018-11-27 | Life Technologies Corporation | Dual labeling methods for measuring cellular proliferation |
US8148503B2 (en) | 2008-06-11 | 2012-04-03 | Lasergen, Inc. | Nucleotides and nucleosides and methods for their use in DNA sequencing |
US8877905B2 (en) | 2008-06-11 | 2014-11-04 | Lasergen, Inc. | Nucleotides and nucleosides and methods for their use in DNA sequencing |
US8497360B2 (en) | 2008-06-11 | 2013-07-30 | Lasergen, Inc. | Nucleotides and nucleosides and methods for their use in DNA sequencing |
US8741571B2 (en) | 2008-07-02 | 2014-06-03 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US9079148B2 (en) | 2008-07-02 | 2015-07-14 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US8399192B2 (en) | 2008-07-02 | 2013-03-19 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US9677069B2 (en) | 2008-07-02 | 2017-06-13 | Illumina Cambridge Limited | Nucleic acid arrays of spatially discrete features on a surface |
US10287577B2 (en) | 2008-07-02 | 2019-05-14 | Illumina Cambridge Ltd. | Nucleic acid arrays of spatially discrete features on a surface |
US8198028B2 (en) | 2008-07-02 | 2012-06-12 | Illumina Cambridge Limited | Using populations of beads for the fabrication of arrays on surfaces |
US11596908B2 (en) | 2008-07-18 | 2023-03-07 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US10533998B2 (en) | 2008-07-18 | 2020-01-14 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US12038438B2 (en) | 2008-07-18 | 2024-07-16 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US11511242B2 (en) | 2008-07-18 | 2022-11-29 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US11534727B2 (en) | 2008-07-18 | 2022-12-27 | Bio-Rad Laboratories, Inc. | Droplet libraries |
US10577601B2 (en) | 2008-09-12 | 2020-03-03 | University Of Washington | Error detection in sequence tag directed subassemblies of short sequencing reads |
US11505795B2 (en) | 2008-09-12 | 2022-11-22 | University Of Washington | Error detection in sequence tag directed sequencing reads |
US10227585B2 (en) | 2008-09-12 | 2019-03-12 | University Of Washington | Sequence tag directed subassembly of short sequencing reads into long sequencing reads |
US11866780B2 (en) | 2008-10-02 | 2024-01-09 | Illumina Cambridge Limited | Nucleic acid sample enrichment for sequencing applications |
US8895268B2 (en) | 2008-10-22 | 2014-11-25 | Illumina, Inc. | Preservation of information related to genomic DNA methylation |
US8541207B2 (en) | 2008-10-22 | 2013-09-24 | Illumina, Inc. | Preservation of information related to genomic DNA methylation |
US9605311B2 (en) | 2008-10-22 | 2017-03-28 | Illumina, Inc. | Tandem sequencing top and bottom strands of double stranded nucleic acid using arrays configured for single molecule detection |
US10174372B2 (en) | 2008-10-22 | 2019-01-08 | Illumina, Inc. | Preservation of information related to genomic DNA methylation |
WO2010048337A2 (en) | 2008-10-22 | 2010-04-29 | Illumina, Inc. | Preservation of information related to genomic dna methylation |
US8236532B2 (en) | 2008-12-23 | 2012-08-07 | Illumina, Inc. | Multibase delivery for long reads in sequencing by synthesis protocols |
US9416415B2 (en) | 2008-12-23 | 2016-08-16 | Illumina, Inc. | Method of sequencing nucleic acid colonies formed on a surface by re-seeding |
US8476022B2 (en) | 2008-12-23 | 2013-07-02 | Illumina, Inc. | Method of making an array of nucleic acid colonies |
EP2607496A1 (en) | 2008-12-23 | 2013-06-26 | Illumina, Inc. | Methods useful in nucleic acid sequencing protocols |
US8709729B2 (en) | 2008-12-23 | 2014-04-29 | Illumina, Inc. | Method of making an array of nucleic acid colonies |
US9005929B2 (en) | 2008-12-23 | 2015-04-14 | Illumina, Inc. | Multibase delivery for long reads in sequencing by synthesis protocols |
US10167506B2 (en) | 2008-12-23 | 2019-01-01 | Illumina, Inc. | Method of sequencing nucleic acid colonies formed on a patterned surface by re-seeding |
WO2010082815A1 (en) | 2009-01-13 | 2010-07-22 | Keygene N.V. | Novel genome sequencing strategies |
US11268887B2 (en) | 2009-03-23 | 2022-03-08 | Bio-Rad Laboratories, Inc. | Manipulation of microfluidic droplets |
US9322050B2 (en) * | 2009-04-23 | 2016-04-26 | Intelligent Bio-Systems, Inc. | Hydroxymethyl linkers for labeling nucleotides |
US20140045175A1 (en) * | 2009-04-23 | 2014-02-13 | Intelligent Biosystems, Inc. | Hydroxymethyl Linkers For Labeling Nucleotides |
US10161000B2 (en) | 2009-04-23 | 2018-12-25 | Qiagen Waltham, Inc. | Hydroxymethyl linkers for labeling nucleotides |
US11840730B1 (en) | 2009-04-30 | 2023-12-12 | Molecular Loop Biosciences, Inc. | Methods and compositions for evaluating genetic markers |
US10036063B2 (en) | 2009-07-24 | 2018-07-31 | Illumina, Inc. | Method for sequencing a polynucleotide template |
EP2669387A1 (en) | 2009-08-25 | 2013-12-04 | Illumina, Inc. | Methods for selecting and amplifying polynucleotides |
EP3133169A1 (en) | 2009-08-25 | 2017-02-22 | Illumina, Inc. | Methods for selecting and amplifying polynucleotides |
US10520500B2 (en) | 2009-10-09 | 2019-12-31 | Abdeslam El Harrak | Labelled silica-based nanomaterial with enhanced properties and uses thereof |
WO2011050938A1 (en) | 2009-10-26 | 2011-05-05 | Genovoxx Gmbh | Conjugates of nucleotides and method for the application thereof |
DE102010049607A1 (en) | 2009-10-26 | 2011-06-30 | Becker, Claus, Prof., 76470 | Conjugates of nucleotides and methods for their use |
US10837883B2 (en) | 2009-12-23 | 2020-11-17 | Bio-Rad Laboratories, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
WO2011093939A1 (en) | 2010-02-01 | 2011-08-04 | Illumina, Inc. | Focusing methods and optical systems and assemblies using the same |
US11254968B2 (en) | 2010-02-12 | 2022-02-22 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US11390917B2 (en) | 2010-02-12 | 2022-07-19 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US9074242B2 (en) | 2010-02-12 | 2015-07-07 | Raindance Technologies, Inc. | Digital analyte analysis |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US10808279B2 (en) | 2010-02-12 | 2020-10-20 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
US10428363B2 (en) | 2010-02-23 | 2019-10-01 | Illumina Cambridge Limited | Amplification methods to minimise sequence specific bias |
US9469872B2 (en) | 2010-02-23 | 2016-10-18 | Illumina Cambridge Limited | Amplification methods to minimise sequence specific bias |
US8759037B2 (en) | 2010-02-23 | 2014-06-24 | Illumina Cambridge Limited | Amplification methods to minimise sequence specific bias |
US8748789B2 (en) | 2010-03-06 | 2014-06-10 | Illumina, Inc. | Assay instrument for detecting optical signals from samples |
DE202011003570U1 (en) | 2010-03-06 | 2012-01-30 | Illumina, Inc. | Systems and apparatus for detecting optical signals from a sample |
US8481903B2 (en) | 2010-03-06 | 2013-07-09 | Alexander Triener | Systems, methods, and apparatuses including a moveable optical component for detecting optical signals from a sample |
WO2011112465A1 (en) | 2010-03-06 | 2011-09-15 | Illumina, Inc. | Systems, methods, and apparatuses for detecting optical signals from a sample |
US9139875B2 (en) | 2010-03-06 | 2015-09-22 | Illumina, Inc. | Assay instrument for detecting optical signals from samples having a controlled optics adjustment system based on the priority statuses of the samples |
US10480022B2 (en) | 2010-04-05 | 2019-11-19 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
US10662467B2 (en) | 2010-04-05 | 2020-05-26 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
US11279975B2 (en) | 2010-08-27 | 2022-03-22 | Illumina Cambridge Limited | Methods for sequencing polynucleotides |
EP3205730A1 (en) | 2010-08-27 | 2017-08-16 | Illumina Cambridge Limited | Methods for paired-end sequencing of polynucleotides |
US9029103B2 (en) | 2010-08-27 | 2015-05-12 | Illumina Cambridge Limited | Methods for sequencing polynucleotides |
WO2012025250A1 (en) | 2010-08-27 | 2012-03-01 | Illumina Cambridge Ltd. | Methods for paired - end sequencing of polynucleotides |
US10329613B2 (en) | 2010-08-27 | 2019-06-25 | Illumina Cambridge Limited | Methods for sequencing polynucleotides |
EP2801623A1 (en) | 2010-08-27 | 2014-11-12 | Illumina Cambridge Limited | Methods for paired-end sequencing of polynucleotides |
WO2012034007A2 (en) | 2010-09-10 | 2012-03-15 | Bio-Rad Laboratories, Inc. | Size selection of dna for chromatin analysis |
US11635427B2 (en) | 2010-09-30 | 2023-04-25 | Bio-Rad Laboratories, Inc. | Sandwich assays in droplets |
WO2012061036A1 (en) | 2010-11-03 | 2012-05-10 | Illumina, Inc. | Reducing adapter dimer formation |
US8575071B2 (en) | 2010-11-03 | 2013-11-05 | Illumina, Inc. | Reducing adapter dimer formation |
US10233443B2 (en) | 2010-11-03 | 2019-03-19 | Illumina, Inc. | Reducing adapter dimer formation |
US9506055B2 (en) | 2010-11-03 | 2016-11-29 | Illumina, Inc. | Reducing adapter dimer formation |
US11041852B2 (en) | 2010-12-23 | 2021-06-22 | Molecular Loop Biosciences, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
US11041851B2 (en) | 2010-12-23 | 2021-06-22 | Molecular Loop Biosciences, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
US11768200B2 (en) | 2010-12-23 | 2023-09-26 | Molecular Loop Biosciences, Inc. | Methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction |
WO2012096703A1 (en) | 2011-01-10 | 2012-07-19 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US11697116B2 (en) | 2011-01-10 | 2023-07-11 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US11117130B2 (en) | 2011-01-10 | 2021-09-14 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US8951781B2 (en) | 2011-01-10 | 2015-02-10 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US11938479B2 (en) | 2011-01-10 | 2024-03-26 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US11559805B2 (en) | 2011-01-10 | 2023-01-24 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
US10220386B2 (en) | 2011-01-10 | 2019-03-05 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
EP3714978A1 (en) | 2011-01-10 | 2020-09-30 | Illumina, Inc. | Systems, methods, and apparatuses to image a sample for biological or chemical analysis |
EP3378564A1 (en) | 2011-01-10 | 2018-09-26 | Illumina Inc. | Fluidic device holder |
WO2012106081A2 (en) | 2011-01-31 | 2012-08-09 | Illumina, Inc. | Methods for reducing nucleic acid damage |
US11299730B2 (en) | 2011-02-02 | 2022-04-12 | University Of Washington Through Its Center For Commercialization | Massively parallel contiguity mapping |
US11999951B2 (en) | 2011-02-02 | 2024-06-04 | University Of Washington Through Its Center For Commercialization | Massively parallel contiguity mapping |
US10457936B2 (en) | 2011-02-02 | 2019-10-29 | University Of Washington Through Its Center For Commercialization | Massively parallel contiguity mapping |
US10246705B2 (en) | 2011-02-10 | 2019-04-02 | Ilumina, Inc. | Linking sequence reads using paired code tags |
US11993772B2 (en) | 2011-02-10 | 2024-05-28 | Illumina, Inc. | Linking sequence reads using paired code tags |
US11077415B2 (en) | 2011-02-11 | 2021-08-03 | Bio-Rad Laboratories, Inc. | Methods for forming mixed droplets |
US11965877B2 (en) | 2011-02-18 | 2024-04-23 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11768198B2 (en) | 2011-02-18 | 2023-09-26 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11168353B2 (en) | 2011-02-18 | 2021-11-09 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
EP3736281A1 (en) | 2011-02-18 | 2020-11-11 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11747327B2 (en) | 2011-02-18 | 2023-09-05 | Bio-Rad Laboratories, Inc. | Compositions and methods for molecular labeling |
US11788122B2 (en) | 2011-04-13 | 2023-10-17 | 10X Genomics Sweden Ab | Methods of detecting analytes |
US11795498B2 (en) | 2011-04-13 | 2023-10-24 | 10X Genomics Sweden Ab | Methods of detecting analytes |
US11352659B2 (en) | 2011-04-13 | 2022-06-07 | Spatial Transcriptomics Ab | Methods of detecting analytes |
US11479809B2 (en) | 2011-04-13 | 2022-10-25 | Spatial Transcriptomics Ab | Methods of detecting analytes |
DE102012008375A1 (en) | 2011-04-27 | 2012-10-31 | Genovoxx Gmbh | Methods and components for the detection of nucleic acid chains |
WO2012150035A1 (en) | 2011-05-04 | 2012-11-08 | Genovoxx Gmbh | Nucleoside-triphosphate conjugate and methods for the use thereof |
DE102012008759A1 (en) | 2011-05-04 | 2012-11-08 | Genovoxx Gmbh | Nucleoside-triphosphate conjugates and methods for their use |
US9624539B2 (en) | 2011-05-23 | 2017-04-18 | The Trustees Of Columbia University In The City Of New York | DNA sequencing by synthesis using Raman and infrared spectroscopy detection |
US11754499B2 (en) | 2011-06-02 | 2023-09-12 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
US10787698B2 (en) | 2011-06-09 | 2020-09-29 | Illumina, Inc. | Patterned flow-cells useful for nucleic acid analysis |
EP2980226A1 (en) | 2011-07-08 | 2016-02-03 | Keygene N.V. | Sequence based genotyping based on oligonucleotide ligation assays |
WO2013009175A1 (en) | 2011-07-08 | 2013-01-17 | Keygene N.V. | Sequence based genotyping based on oligonucleotide ligation assays |
US11898193B2 (en) | 2011-07-20 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Manipulating droplet size |
US10041115B2 (en) | 2011-09-13 | 2018-08-07 | Lasergen, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
US11001886B2 (en) | 2011-09-13 | 2021-05-11 | Agilent Technologies, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
US9689035B2 (en) | 2011-09-13 | 2017-06-27 | Lasergen, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
US9399798B2 (en) | 2011-09-13 | 2016-07-26 | Lasergen, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
US8889860B2 (en) | 2011-09-13 | 2014-11-18 | Lasergen, Inc. | 3′-OH unblocked, fast photocleavable terminating nucleotides and methods for nucleic acid sequencing |
US10287629B2 (en) | 2011-09-23 | 2019-05-14 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
EP3623481A1 (en) * | 2011-09-23 | 2020-03-18 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
US11827932B2 (en) | 2011-09-23 | 2023-11-28 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
US10900077B2 (en) | 2011-09-23 | 2021-01-26 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
US9453258B2 (en) | 2011-09-23 | 2016-09-27 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
EP2761026A1 (en) * | 2011-09-29 | 2014-08-06 | Illumina, Inc. | Continuous extension and deblocking in reactions for nucleic acid synthesis and sequencing |
US10378051B2 (en) | 2011-09-29 | 2019-08-13 | Illumina Cambridge Limited | Continuous extension and deblocking in reactions for nucleic acids synthesis and sequencing |
US9228233B2 (en) | 2011-10-17 | 2016-01-05 | Good Start Genetics, Inc. | Analysis methods |
US10370710B2 (en) | 2011-10-17 | 2019-08-06 | Good Start Genetics, Inc. | Analysis methods |
US9822409B2 (en) | 2011-10-17 | 2017-11-21 | Good Start Genetics, Inc. | Analysis methods |
US11834704B2 (en) | 2011-10-28 | 2023-12-05 | Illumina, Inc. | Microarray fabrication system and method |
US10280454B2 (en) | 2011-10-28 | 2019-05-07 | Illumina, Inc. | Microarray fabrication system and method |
US11060135B2 (en) | 2011-10-28 | 2021-07-13 | Illumina, Inc. | Microarray fabrication system and method |
US9670535B2 (en) | 2011-10-28 | 2017-06-06 | Illumina, Inc. | Microarray fabrication system and method |
WO2013070627A2 (en) | 2011-11-07 | 2013-05-16 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
US9309571B2 (en) | 2011-11-07 | 2016-04-12 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
US10167505B2 (en) | 2011-11-07 | 2019-01-01 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
US8637242B2 (en) | 2011-11-07 | 2014-01-28 | Illumina, Inc. | Integrated sequencing apparatuses and methods of use |
WO2013117595A2 (en) | 2012-02-07 | 2013-08-15 | Illumina Cambridge Limited | Targeted enrichment and amplification of nucleic acids on a support |
WO2013126741A1 (en) | 2012-02-24 | 2013-08-29 | Raindance Technologies, Inc. | Labeling and sample preparation for sequencing |
EP3309262A1 (en) | 2012-02-24 | 2018-04-18 | Raindance Technologies, Inc. | Labeling and sample preparation for sequencing |
EP3037552A1 (en) | 2012-03-06 | 2016-06-29 | Illumina Cambridge Limited | Improved methods of nucleic acid sequencing |
WO2013131962A1 (en) | 2012-03-06 | 2013-09-12 | Illumina Cambridge Limited | Improved methods of nucleic acid sequencing |
WO2013148970A1 (en) | 2012-03-30 | 2013-10-03 | Illumina, Inc. | Methods and systems for determining fetal chromosomal abnormalities |
US9650669B2 (en) | 2012-04-03 | 2017-05-16 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
EP4219012A1 (en) | 2012-04-03 | 2023-08-02 | Illumina, Inc. | Method of imaging a substrate comprising fluorescent features and use of the method in nucleic acid sequencing |
US11565267B2 (en) | 2012-04-03 | 2023-01-31 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
WO2013151622A1 (en) | 2012-04-03 | 2013-10-10 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
US10549281B2 (en) | 2012-04-03 | 2020-02-04 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
US9193996B2 (en) | 2012-04-03 | 2015-11-24 | Illumina, Inc. | Integrated optoelectronic read head and fluidic cartridge useful for nucleic acid sequencing |
US11667965B2 (en) | 2012-04-04 | 2023-06-06 | Invitae Corporation | Sequence assembly |
US11149308B2 (en) | 2012-04-04 | 2021-10-19 | Invitae Corporation | Sequence assembly |
US11155863B2 (en) | 2012-04-04 | 2021-10-26 | Invitae Corporation | Sequence assembly |
US10604799B2 (en) | 2012-04-04 | 2020-03-31 | Molecular Loop Biosolutions, Llc | Sequence assembly |
US9298804B2 (en) | 2012-04-09 | 2016-03-29 | Good Start Genetics, Inc. | Variant database |
US10428367B2 (en) | 2012-04-11 | 2019-10-01 | Illumina, Inc. | Portable genetic detection and analysis system and method |
US11634746B2 (en) | 2012-04-11 | 2023-04-25 | Illumina, Inc. | Portable genetic detection and analysis system and method |
US10683533B2 (en) | 2012-04-16 | 2020-06-16 | Molecular Loop Biosolutions, Llc | Capture reactions |
US10227635B2 (en) | 2012-04-16 | 2019-03-12 | Molecular Loop Biosolutions, Llc | Capture reactions |
EP3438285A1 (en) | 2012-05-02 | 2019-02-06 | Ibis Biosciences, Inc. | Dna sequencing |
US10202642B2 (en) | 2012-05-02 | 2019-02-12 | Ibis Biosciences, Inc. | DNA sequencing |
EP3783111A1 (en) | 2012-05-02 | 2021-02-24 | Ibis Biosciences, Inc. | Dna sequencing |
EP3789502A1 (en) | 2012-05-02 | 2021-03-10 | Ibis Biosciences, Inc. | Dna sequencing |
EP3438286A1 (en) | 2012-05-02 | 2019-02-06 | Ibis Biosciences, Inc. | Dna sequencing |
US10584377B2 (en) | 2012-05-02 | 2020-03-10 | Ibis Biosciences, Inc. | DNA sequencing |
US11359236B2 (en) | 2012-05-02 | 2022-06-14 | Ibis Biosciences, Inc. | DNA sequencing |
US10544454B2 (en) | 2012-05-02 | 2020-01-28 | Ibis Biosciences, Inc. | DNA sequencing |
US10954561B2 (en) | 2012-06-08 | 2021-03-23 | Illumina, Inc. | Polymer coatings |
US12060609B2 (en) | 2012-06-08 | 2024-08-13 | Illumina, Inc. | Polymer coatings |
EP3792320A1 (en) | 2012-06-08 | 2021-03-17 | Illumina, Inc. | Polymer coatings |
US10266891B2 (en) | 2012-06-08 | 2019-04-23 | Illumina, Inc. | Polymer coatings |
US9012022B2 (en) | 2012-06-08 | 2015-04-21 | Illumina, Inc. | Polymer coatings |
WO2013184796A1 (en) | 2012-06-08 | 2013-12-12 | Illumina, Inc. | Polymer coatings |
US11702694B2 (en) | 2012-06-08 | 2023-07-18 | Illumina, Inc. | Polymer coatings |
US9752186B2 (en) | 2012-06-08 | 2017-09-05 | Illumina, Inc. | Polymer coatings |
US10385384B2 (en) | 2012-06-15 | 2019-08-20 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US9169513B2 (en) | 2012-06-15 | 2015-10-27 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US11254976B2 (en) | 2012-06-15 | 2022-02-22 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
WO2013188582A1 (en) | 2012-06-15 | 2013-12-19 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
EP3366781A1 (en) | 2012-06-15 | 2018-08-29 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US9758816B2 (en) | 2012-06-15 | 2017-09-12 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US8895249B2 (en) | 2012-06-15 | 2014-11-25 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
EP3243937A1 (en) | 2012-07-17 | 2017-11-15 | Counsyl, Inc. | System and methods for detecting genetic variation |
EP3699577A2 (en) | 2012-08-20 | 2020-08-26 | Illumina, Inc. | System for fluorescence lifetime based sequencing |
US10895534B2 (en) | 2012-08-20 | 2021-01-19 | Illumina, Inc. | Method and system for fluorescence lifetime based sequencing |
US11841322B2 (en) | 2012-08-20 | 2023-12-12 | Illumina, Inc. | Method and system for fluorescence lifetime based sequencing |
EP3594362A1 (en) | 2012-10-23 | 2020-01-15 | Illumina, Inc. | Method and systems for determining haplotypes in a sample |
WO2014066217A1 (en) | 2012-10-23 | 2014-05-01 | Illumina, Inc. | Hla typing using selective amplification and sequencing |
US9092401B2 (en) | 2012-10-31 | 2015-07-28 | Counsyl, Inc. | System and methods for detecting genetic variation |
EP4417692A2 (en) | 2013-01-09 | 2024-08-21 | Illumina Cambridge Limited | Sample preparation on a solid support |
EP3486331A1 (en) | 2013-01-09 | 2019-05-22 | Illumina Cambridge Limited | Sample preparation on a solid support |
US10988760B2 (en) | 2013-01-09 | 2021-04-27 | Illumina Cambridge Limited | Sample preparation on a solid support |
US10041066B2 (en) | 2013-01-09 | 2018-08-07 | Illumina Cambridge Limited | Sample preparation on a solid support |
US11970695B2 (en) | 2013-01-09 | 2024-04-30 | Illumina Cambridge Limited | Sample preparation on a solid support |
WO2014108810A2 (en) | 2013-01-09 | 2014-07-17 | Lumina Cambridge Limited | Sample preparation on a solid support |
WO2014116851A2 (en) | 2013-01-25 | 2014-07-31 | Illumina, Inc. | Methods and systems for using a cloud computing environment to share biological related data |
US9805407B2 (en) | 2013-01-25 | 2017-10-31 | Illumina, Inc. | Methods and systems for using a cloud computing environment to configure and sell a biological sample preparation cartridge and share related data |
US10217156B2 (en) | 2013-01-25 | 2019-02-26 | Illumina, Inc. | Methods and systems for using a cloud computing environment to share biological related data |
WO2014133905A1 (en) | 2013-02-26 | 2014-09-04 | Illumina, Inc. | Gel patterned surfaces |
US10668444B2 (en) | 2013-02-26 | 2020-06-02 | Illumina, Inc. | Gel patterned surfaces |
US11173466B2 (en) | 2013-02-26 | 2021-11-16 | Illumina, Inc. | Gel patterned surfaces |
EP3603794A1 (en) | 2013-02-26 | 2020-02-05 | Illumina, Inc. | Gel patterned surfaces |
EP3834924A1 (en) | 2013-02-26 | 2021-06-16 | Illumina Inc | Gel patterned surfaces |
US9512422B2 (en) | 2013-02-26 | 2016-12-06 | Illumina, Inc. | Gel patterned surfaces |
WO2014135669A1 (en) | 2013-03-08 | 2014-09-12 | Roche Diagnostics Gmbh | Egfr mutation blood testing |
WO2014135221A1 (en) | 2013-03-08 | 2014-09-12 | Illumina Cambridge Ltd | Polymethine compounds and their use as fluorescent labels |
WO2014135223A1 (en) | 2013-03-08 | 2014-09-12 | Illumina Cambridge Ltd | Rhodamine compounds and their use as fluorescent labels |
WO2014142841A1 (en) | 2013-03-13 | 2014-09-18 | Illumina, Inc. | Multilayer fluidic devices and methods for their fabrication |
US10807089B2 (en) | 2013-03-13 | 2020-10-20 | Illumina, Inc. | Multilayer fluidic devices and methods for their fabrication |
US11319534B2 (en) | 2013-03-13 | 2022-05-03 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
US10557133B2 (en) | 2013-03-13 | 2020-02-11 | Illumina, Inc. | Methods and compositions for nucleic acid sequencing |
US11110452B2 (en) | 2013-03-13 | 2021-09-07 | Illumina, Inc. | Multilayer fluidic devices and methods for their fabrication |
US12017214B2 (en) | 2013-03-13 | 2024-06-25 | Illumina, Inc. | Multilayer fluidic devices and methods for their fabrication |
US10202637B2 (en) | 2013-03-14 | 2019-02-12 | Molecular Loop Biosolutions, Llc | Methods for analyzing nucleic acid |
EP2971070B1 (en) | 2013-03-14 | 2018-04-25 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US9677124B2 (en) | 2013-03-14 | 2017-06-13 | Good Start Genetics, Inc. | Methods for analyzing nucleic acids |
US11781182B2 (en) | 2013-03-14 | 2023-10-10 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US10745751B2 (en) | 2013-03-14 | 2020-08-18 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
EP2971070B2 (en) † | 2013-03-14 | 2021-03-03 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US9115387B2 (en) | 2013-03-14 | 2015-08-25 | Good Start Genetics, Inc. | Methods for analyzing nucleic acids |
WO2014142921A1 (en) | 2013-03-14 | 2014-09-18 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US10421996B2 (en) | 2013-03-14 | 2019-09-24 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
US10982277B2 (en) | 2013-03-15 | 2021-04-20 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US9593373B2 (en) | 2013-03-15 | 2017-03-14 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US9193998B2 (en) | 2013-03-15 | 2015-11-24 | Illumina, Inc. | Super resolution imaging |
US10249038B2 (en) | 2013-03-15 | 2019-04-02 | Qiagen Sciences, Llc | Flow cell alignment methods and systems |
EP3388442A1 (en) | 2013-03-15 | 2018-10-17 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US10407721B2 (en) | 2013-03-15 | 2019-09-10 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
WO2014139596A1 (en) * | 2013-03-15 | 2014-09-18 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US20170166961A1 (en) | 2013-03-15 | 2017-06-15 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US10648026B2 (en) | 2013-03-15 | 2020-05-12 | The Trustees Of Columbia University In The City Of New York | Raman cluster tagged molecules for biological imaging |
US20200087725A1 (en) * | 2013-03-15 | 2020-03-19 | Illumina Cambridge Limited | Modified nucleosides or nucleotides |
US11697847B2 (en) | 2013-03-15 | 2023-07-11 | Illumina, Inc. | Super resolution imaging |
WO2014144569A1 (en) | 2013-03-15 | 2014-09-18 | Illumina, Inc. | Super resolution imaging |
US9535920B2 (en) | 2013-06-03 | 2017-01-03 | Good Start Genetics, Inc. | Methods and systems for storing sequence read data |
US10706017B2 (en) | 2013-06-03 | 2020-07-07 | Good Start Genetics, Inc. | Methods and systems for storing sequence read data |
US10975210B2 (en) | 2013-07-01 | 2021-04-13 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
WO2015002813A1 (en) | 2013-07-01 | 2015-01-08 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
EP3919624A2 (en) | 2013-07-01 | 2021-12-08 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
US11618808B2 (en) | 2013-07-01 | 2023-04-04 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
EP3431614A1 (en) | 2013-07-01 | 2019-01-23 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
US9994687B2 (en) | 2013-07-01 | 2018-06-12 | Illumina, Inc. | Catalyst-free surface functionalization and polymer grafting |
US9193999B2 (en) | 2013-07-03 | 2015-11-24 | Illumina, Inc. | Sequencing by orthogonal synthesis |
US9574235B2 (en) | 2013-07-03 | 2017-02-21 | Illumina, Inc. | Sequencing by orthogonal synthesis |
EP3241913A1 (en) | 2013-07-03 | 2017-11-08 | Illumina, Inc. | System for sequencing by orthogonal synthesis |
WO2015002789A1 (en) | 2013-07-03 | 2015-01-08 | Illumina, Inc. | Sequencing by orthogonal synthesis |
US9777325B2 (en) | 2013-08-08 | 2017-10-03 | Illumina, Inc. | Fluidic system for reagent delivery to a flow cell |
US9410977B2 (en) | 2013-08-08 | 2016-08-09 | Illumina, Inc. | Fluidic system for reagent delivery to a flow cell |
USRE48993E1 (en) | 2013-08-08 | 2022-03-29 | Illumina, Inc. | Fluidic system for reagent delivery to a flow cell |
EP4190889A1 (en) | 2013-08-08 | 2023-06-07 | Illumina, Inc. | Fluidic system for reagent delivery to a flow cell |
DE202014006405U1 (en) | 2013-08-08 | 2014-12-08 | Illumina, Inc. | Fluid system for reagent delivery to a flow cell |
WO2015021228A1 (en) | 2013-08-08 | 2015-02-12 | Illumina, Inc. | Fluidic system for reagent delivery to a flow cell |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US11041203B2 (en) | 2013-10-18 | 2021-06-22 | Molecular Loop Biosolutions, Inc. | Methods for assessing a genomic region of a subject |
US12077822B2 (en) | 2013-10-18 | 2024-09-03 | Molecular Loop Biosciences, Inc. | Methods for determining carrier status |
US10851414B2 (en) | 2013-10-18 | 2020-12-01 | Good Start Genetics, Inc. | Methods for determining carrier status |
US10540783B2 (en) | 2013-11-01 | 2020-01-21 | Illumina, Inc. | Image analysis useful for patterned objects |
US11308640B2 (en) | 2013-11-01 | 2022-04-19 | Illumina, Inc. | Image analysis useful for patterned objects |
WO2015084985A2 (en) | 2013-12-03 | 2015-06-11 | Illumina, Inc. | Methods and systems for analyzing image data |
EP3715467A1 (en) | 2013-12-03 | 2020-09-30 | Illumina, Inc. | Methods and systems for analyzing image data |
EP3940082A1 (en) | 2013-12-03 | 2022-01-19 | Illumina, Inc. | Methods and systems for analyzing image data |
US11719637B2 (en) | 2013-12-10 | 2023-08-08 | Illumina, Inc. | Biosensors for biological or chemical analysis and methods of manufacturing the same |
US11181478B2 (en) | 2013-12-10 | 2021-11-23 | Illumina, Inc. | Biosensors for biological or chemical analysis and methods of manufacturing the same |
EP4220137A1 (en) | 2013-12-10 | 2023-08-02 | Illumina, Inc. | Biosensors for biological or chemical analysis and methods of manufacturing the same |
US11174509B2 (en) | 2013-12-12 | 2021-11-16 | Bio-Rad Laboratories, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US11149310B2 (en) | 2013-12-20 | 2021-10-19 | Illumina, Inc. | Preserving genomic connectivity information in fragmented genomic DNA samples |
WO2015095226A2 (en) | 2013-12-20 | 2015-06-25 | Illumina, Inc. | Preserving genomic connectivity information in fragmented genomic dna samples |
US10246746B2 (en) | 2013-12-20 | 2019-04-02 | Illumina, Inc. | Preserving genomic connectivity information in fragmented genomic DNA samples |
EP3957750A1 (en) | 2013-12-20 | 2022-02-23 | Illumina, Inc. | Preserving genomic connectivity information in fragmented genomic dna samples |
WO2015100373A2 (en) | 2013-12-23 | 2015-07-02 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
EP3778890A1 (en) | 2013-12-23 | 2021-02-17 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
US10537889B2 (en) | 2013-12-31 | 2020-01-21 | Illumina, Inc. | Addressable flow cell using patterned electrodes |
WO2015103225A1 (en) | 2013-12-31 | 2015-07-09 | Illumina, Inc. | Addressable flow cell using patterned electrodes |
US10865444B2 (en) | 2014-01-16 | 2020-12-15 | Illumina, Inc. | Amplicon preparation and sequencing on solid supports |
WO2015106941A1 (en) | 2014-01-16 | 2015-07-23 | Illumina Cambridge Limited | Polynucleotide modification on solid support |
WO2015108663A1 (en) | 2014-01-16 | 2015-07-23 | Illumina, Inc. | Amplicon preparation and sequencing on solid supports |
EP3910069A1 (en) | 2014-02-18 | 2021-11-17 | Illumina, Inc. | Methods and composition for dna profiling |
EP3698874A1 (en) | 2014-03-11 | 2020-08-26 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making the same |
US10767219B2 (en) | 2014-03-11 | 2020-09-08 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making and using same |
US11174513B2 (en) | 2014-03-11 | 2021-11-16 | Illumina, Inc. | Disposable, integrated microfluidic cartridge and methods of making and using same |
US11685941B2 (en) | 2014-04-17 | 2023-06-27 | Dna Script | Method for synthesizing nucleic acids, in particular long nucleic acids, use of said method and kit for implementing said method |
US10837040B2 (en) | 2014-04-17 | 2020-11-17 | Dna Script | Method for synthesizing nucleic acids, in particular long nucleic acids, use of said method and kit for implementing said method |
US10913964B2 (en) | 2014-04-17 | 2021-02-09 | Dna Script | Method for synthesizing nucleic acids, in particular long nucleic acids, use of said method and kit for implementing said method |
EP3680333A1 (en) | 2014-04-29 | 2020-07-15 | Illumina, Inc. | Multiplexed single cell expression analysis using template switch and tagmentation |
EP3828167A1 (en) | 2014-05-07 | 2021-06-02 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
US11053548B2 (en) | 2014-05-12 | 2021-07-06 | Good Start Genetics, Inc. | Methods for detecting aneuploidy |
WO2015175832A1 (en) | 2014-05-16 | 2015-11-19 | Illumina, Inc. | Nucleic acid synthesis techniques |
US10570447B2 (en) | 2014-05-16 | 2020-02-25 | Illumina, Inc. | Nucleic acid synthesis techniques |
US11590494B2 (en) | 2014-05-27 | 2023-02-28 | Illumina, Inc. | Systems and methods for biochemical analysis including a base instrument and a removable cartridge |
WO2015183871A1 (en) | 2014-05-27 | 2015-12-03 | Illumina, Inc. | Systems and methods for biochemical analysis including a base instrument and a removable cartridge |
US11254981B2 (en) | 2014-06-03 | 2022-02-22 | Illumina, Inc. | Compositions, systems, and methods for detecting events using tethers anchored to or adjacent to nanopores |
US10364463B2 (en) | 2014-06-03 | 2019-07-30 | Illumina, Inc. | Compositions, systems, and methods for detecting events using tethers anchored to or adjacent to nanopores |
US9708655B2 (en) | 2014-06-03 | 2017-07-18 | Illumina, Inc. | Compositions, systems, and methods for detecting events using tethers anchored to or adjacent to nanopores |
EP3683318A1 (en) | 2014-06-03 | 2020-07-22 | Illumina, Inc. | Compositions, systems, and methods for detecting events using tethers anchored to or adjacent to nanopores |
EP4039815A1 (en) | 2014-06-09 | 2022-08-10 | Illumina Cambridge Limited | Sample preparation for nucleic acid amplification |
EP3699289A1 (en) | 2014-06-09 | 2020-08-26 | Illumina Cambridge Limited | Sample preparation for nucleic acid amplification |
US11299765B2 (en) | 2014-06-13 | 2022-04-12 | Illumina Cambridge Limited | Methods and compositions for preparing sequencing libraries |
US10443087B2 (en) | 2014-06-13 | 2019-10-15 | Illumina Cambridge Limited | Methods and compositions for preparing sequencing libraries |
EP3754020A1 (en) | 2014-06-26 | 2020-12-23 | Illumina, Inc. | Library preparation of tagged nucleic acid using single tube add-on protocol |
WO2015200609A1 (en) | 2014-06-26 | 2015-12-30 | Illumina, Inc. | Library preparation of tagged nucleic acid using single tube add-on protocol |
US11085041B2 (en) | 2014-06-26 | 2021-08-10 | Illumina, Inc. | Library preparation of tagged nucleic acid |
EP3702471A1 (en) | 2014-06-27 | 2020-09-02 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
WO2015200693A1 (en) | 2014-06-27 | 2015-12-30 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
WO2016003814A1 (en) | 2014-06-30 | 2016-01-07 | Illumina, Inc. | Methods and compositions using one-sided transposition |
US11965158B2 (en) | 2014-06-30 | 2024-04-23 | Illumina, Inc. | Methods and compositions using one-sided transposition |
US10968448B2 (en) | 2014-06-30 | 2021-04-06 | Illumina, Inc. | Methods and compositions using one-sided transposition |
US10577603B2 (en) | 2014-06-30 | 2020-03-03 | Illumina, Inc. | Methods and compositions using one-sided transposition |
US10545115B2 (en) | 2014-07-15 | 2020-01-28 | Illumina, Inc. | Biochemically activated electronic device |
EP3460075A1 (en) | 2014-07-15 | 2019-03-27 | Illumina, Inc. | Biochemically activated electronic device |
US10605766B2 (en) | 2014-07-15 | 2020-03-31 | Illumina, Inc. | Biochemically activated electronic device |
EP3828279A1 (en) | 2014-07-15 | 2021-06-02 | Illumina, Inc. | Biochemically activated electronic device |
WO2016014409A1 (en) | 2014-07-21 | 2016-01-28 | Illumina, Inc. | Polynucleotide enrichment using crispr-cas systems |
EP3564252A1 (en) | 2014-08-08 | 2019-11-06 | Illumina Cambridge Limited | Modified nucleotide linkers |
US9982250B2 (en) | 2014-08-21 | 2018-05-29 | Illumina Cambridge Limited | Reversible surface functionalization |
US10684281B2 (en) | 2014-08-21 | 2020-06-16 | Illumina Cambridge Limited | Reversible surface functionalization |
WO2016026924A1 (en) | 2014-08-21 | 2016-02-25 | Illumina Cambridge Limited | Reversible surface functionalization |
US11199540B2 (en) | 2014-08-21 | 2021-12-14 | Illumina Cambridge Limited | Reversible surface functionalization |
US11059849B2 (en) | 2014-09-02 | 2021-07-13 | Dna Script | Modified nucleotides for synthesis of nucleic acids, a kit containing such nucleotides and their use for the production of synthetic nucleic acid sequences or genes |
US11408024B2 (en) | 2014-09-10 | 2022-08-09 | Molecular Loop Biosciences, Inc. | Methods for selectively suppressing non-target sequences |
WO2016040602A1 (en) | 2014-09-11 | 2016-03-17 | Epicentre Technologies Corporation | Reduced representation bisulfite sequencing using uracil n-glycosylase (ung) and endonuclease iv |
WO2016040607A1 (en) | 2014-09-12 | 2016-03-17 | Illumina, Inc. | Compositions, systems, and methods for detecting the presence of polymer subunits using chemiluminescence |
US10633694B2 (en) | 2014-09-12 | 2020-04-28 | Illumina, Inc. | Compositions, systems, and methods for detecting the presence of polymer subunits using chemiluminescence |
US11629373B2 (en) | 2014-09-12 | 2023-04-18 | Illumina, Inc. | Compositions, systems, and methods for detecting the presence of polymer subunits using chemiluminescence |
WO2016044233A1 (en) | 2014-09-18 | 2016-03-24 | Illumina, Inc. | Methods and systems for analyzing nucleic acid sequencing data |
US10429399B2 (en) | 2014-09-24 | 2019-10-01 | Good Start Genetics, Inc. | Process control for increased robustness of genetic assays |
WO2016054096A1 (en) | 2014-09-30 | 2016-04-07 | Illumina, Inc. | Modified polymerases for improved incorporation of nucleotide analogues |
WO2016061484A2 (en) | 2014-10-16 | 2016-04-21 | Illumina, Inc. | Optical scanning systems for in situ genetic analysis |
US11873480B2 (en) | 2014-10-17 | 2024-01-16 | Illumina Cambridge Limited | Contiguity preserving transposition |
EP3699283A1 (en) | 2014-10-20 | 2020-08-26 | Molecular Assemblies Inc. | Modified template-independent enzymes for polydeoxynucleotide systhesis |
US10190162B2 (en) | 2014-10-23 | 2019-01-29 | Complete Genomics, Inc. | Signal confinement sequencing (SCS) and nucleotide analogues for signal confinement sequencing |
US10577439B2 (en) | 2014-10-31 | 2020-03-03 | Illumina Cambridge Limited | Polymers and DNA copolymer coatings |
EP3632944A1 (en) | 2014-10-31 | 2020-04-08 | Illumina Cambridge Limited | Polymers and dna copolymer coatings |
US11447582B2 (en) | 2014-10-31 | 2022-09-20 | Illumina Cambridge Limited | Polymers and DNA copolymer coatings |
US9815916B2 (en) | 2014-10-31 | 2017-11-14 | Illumina Cambridge Limited | Polymers and DNA copolymer coatings |
EP3970849A1 (en) | 2014-10-31 | 2022-03-23 | Illumina Cambridge Limited | Polymers and dna copolymer coatings |
US10208142B2 (en) | 2014-10-31 | 2019-02-19 | Illumnia Cambridge Limited | Polymers and DNA copolymer coatings |
US10000799B2 (en) | 2014-11-04 | 2018-06-19 | Boreal Genomics, Inc. | Methods of sequencing with linked fragments |
US11827930B2 (en) | 2014-11-04 | 2023-11-28 | Ncan Genomics, Inc. | Methods of sequencing with linked fragments |
US10829813B2 (en) | 2014-11-04 | 2020-11-10 | Boreal Genomics, Inc. | Methods of sequencing with linked fragments |
US11555218B2 (en) | 2014-11-05 | 2023-01-17 | Illumina Cambridge Limited | Sequencing from multiple primers to increase data rate and density |
EP3974538A1 (en) | 2014-11-05 | 2022-03-30 | Illumina Cambridge Limited | Sequencing from multiple primers to increase data rate and density |
WO2016073237A1 (en) | 2014-11-05 | 2016-05-12 | Illumina Cambridge Limited | Reducing dna damage during sample preparation and sequencing using siderophore chelators |
US10619204B2 (en) | 2014-11-11 | 2020-04-14 | Illumina Cambridge Limited | Methods and arrays for producing and sequencing monoclonal clusters of nucleic acid |
US11692223B2 (en) | 2014-11-11 | 2023-07-04 | Illumina Cambridge Limited | Methods and arrays for producing and sequencing monoclonal clusters of nucleic acid |
US10577649B2 (en) | 2014-11-11 | 2020-03-03 | Illumina, Inc. | Polynucleotide amplification using CRISPR-Cas systems |
US12065695B2 (en) | 2014-11-11 | 2024-08-20 | Illumina, Inc. | Polynucleotide amplification using CRISPR-Cas systems |
EP3882356A1 (en) | 2014-12-15 | 2021-09-22 | Illumina, Inc. | Compositions and methods for single molecular placement on a substrate |
US10960377B2 (en) | 2014-12-15 | 2021-03-30 | Illumina, Inc. | Compositions and methods for single molecular placement on a substrate |
US10350570B2 (en) | 2014-12-15 | 2019-07-16 | Illumina, Inc. | Compositions and methods for single molecular placement on a substrate |
US10066259B2 (en) | 2015-01-06 | 2018-09-04 | Good Start Genetics, Inc. | Screening for structural variants |
US11680284B2 (en) | 2015-01-06 | 2023-06-20 | Moledular Loop Biosciences, Inc. | Screening for structural variants |
EP3725893A1 (en) | 2015-02-10 | 2020-10-21 | Illumina, Inc. | Compositions for analyzing cellular components |
WO2016139477A1 (en) * | 2015-03-03 | 2016-09-09 | Nuclera Nucleics Ltd | A process for the preparation of nucleic acid by means of 3'-o-azidomethyl nucleotide triphosphate |
US10576471B2 (en) | 2015-03-20 | 2020-03-03 | Illumina, Inc. | Fluidics cartridge for use in the vertical or substantially vertical position |
US9976174B2 (en) | 2015-03-24 | 2018-05-22 | Illumina Cambridge Limited | Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis |
EP4089398A1 (en) | 2015-03-24 | 2022-11-16 | Illumina, Inc. | Carrier assemblies and systems for imaging samples for biological or chemical analysis |
US11479808B2 (en) | 2015-03-24 | 2022-10-25 | Illumina Cambridge Limited | Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis |
US10584374B2 (en) | 2015-03-24 | 2020-03-10 | Illumina Cambridge Limited | Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis |
EP3783109A1 (en) | 2015-03-31 | 2021-02-24 | Illumina Cambridge Limited | Surface concatamerization of templates |
EP3901281A1 (en) | 2015-04-10 | 2021-10-27 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP3530752A1 (en) | 2015-04-10 | 2019-08-28 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP3901282A1 (en) | 2015-04-10 | 2021-10-27 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
WO2016162309A1 (en) | 2015-04-10 | 2016-10-13 | Spatial Transcriptomics Ab | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP4321627A2 (en) | 2015-04-10 | 2024-02-14 | 10x Genomics Sweden AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP4151748A1 (en) | 2015-04-10 | 2023-03-22 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP4119677A1 (en) | 2015-04-10 | 2023-01-18 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
EP4282977A2 (en) | 2015-04-10 | 2023-11-29 | 10x Genomics Sweden AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
WO2016168386A1 (en) | 2015-04-14 | 2016-10-20 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
US10900030B2 (en) | 2015-04-14 | 2021-01-26 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
US11466268B2 (en) | 2015-04-14 | 2022-10-11 | Illumina, Inc. | Structured substrates for improving detection of light emissions and methods relating to the same |
EP3696536A1 (en) | 2015-04-14 | 2020-08-19 | Illumina, Inc. | A method of manufacturing a substrate and a method of analyzing biomolecules capable of generating light emissions |
US10844428B2 (en) | 2015-04-28 | 2020-11-24 | Illumina, Inc. | Error suppression in sequenced DNA fragments using redundant reads with unique molecular indices (UMIS) |
US11866777B2 (en) | 2015-04-28 | 2024-01-09 | Illumina, Inc. | Error suppression in sequenced DNA fragments using redundant reads with unique molecular indices (UMIS) |
US9868947B2 (en) | 2015-05-04 | 2018-01-16 | Washington University | Compositions and methods for the construction of a random allelic series |
WO2016183029A1 (en) | 2015-05-11 | 2016-11-17 | Illumina, Inc. | Platform for discovery and analysis of therapeutic agents |
EP3822365A1 (en) | 2015-05-11 | 2021-05-19 | Illumina, Inc. | Platform for discovery and analysis of therapeutic agents |
EP3760737A2 (en) | 2015-05-11 | 2021-01-06 | Illumina, Inc. | Platform for discovery and analysis of therapeutic agents |
EP4190912A1 (en) | 2015-05-11 | 2023-06-07 | Illumina, Inc. | Platform for discovery and analysis of therapeutic agents |
US10239909B2 (en) | 2015-05-22 | 2019-03-26 | Illumina Cambridge Limited | Polymethine compounds with long stokes shifts and their use as fluorescent labels |
US10590464B2 (en) | 2015-05-29 | 2020-03-17 | Illumina Cambridge Limited | Enhanced utilization of surface primers in clusters |
EP4046717A2 (en) | 2015-05-29 | 2022-08-24 | Illumina, Inc. | Sample carrier and assay system for conducting designated reactions |
WO2016196358A1 (en) | 2015-05-29 | 2016-12-08 | Epicentre Technologies Corporation | Methods of analyzing nucleic acids |
WO2016196210A2 (en) | 2015-05-29 | 2016-12-08 | Illumina, Inc. | Sample carrier and assay system for conducting designated reactions |
US11970734B2 (en) | 2015-06-03 | 2024-04-30 | Illumina, Inc. | Compositions, systems, and methods for sequencing polynucleotides using tethers anchored to polymerases adjacent to nanopores |
US10648022B2 (en) | 2015-06-03 | 2020-05-12 | Illumina, Inc. | Compositions, systems, and methods for sequencing polynucleotides using tethers anchored to polymerases adjacent to nanopores |
EP3878974A1 (en) | 2015-07-06 | 2021-09-15 | Illumina Cambridge Limited | Sample preparation for nucleic acid amplification |
US10808282B2 (en) | 2015-07-07 | 2020-10-20 | Illumina, Inc. | Selective surface patterning via nanoimprinting |
WO2017009663A1 (en) * | 2015-07-15 | 2017-01-19 | Nuclera Nucleics Ltd | Azidomethyl ether deprotection method |
WO2017015018A1 (en) | 2015-07-17 | 2017-01-26 | Illumina, Inc. | Polymer sheets for sequencing applications |
WO2017019456A2 (en) | 2015-07-27 | 2017-02-02 | Illumina, Inc. | Spatial mapping of nucleic acid sequence information |
WO2017019278A1 (en) | 2015-07-30 | 2017-02-02 | Illumina, Inc. | Orthogonal deblocking of nucleotides |
EP3854884A1 (en) | 2015-08-14 | 2021-07-28 | Illumina, Inc. | Systems and methods using magnetically-responsive sensors for determining a genetic characteristic |
US11512348B2 (en) | 2015-08-14 | 2022-11-29 | Illumina, Inc. | Systems and methods using magnetically-responsive sensors for determining a genetic characteristic |
US10976334B2 (en) | 2015-08-24 | 2021-04-13 | Illumina, Inc. | In-line pressure accumulator and flow-control system for biological or chemical assays |
EP4086357A1 (en) | 2015-08-28 | 2022-11-09 | Illumina, Inc. | Nucleic acid sequence analysis from single cells |
EP4368715A2 (en) | 2015-08-28 | 2024-05-15 | Illumina, Inc. | Nucleic acid sequence analysis from single cells |
US10906044B2 (en) | 2015-09-02 | 2021-02-02 | Illumina Cambridge Limited | Methods of improving droplet operations in fluidic systems with a filler fluid including a surface regenerative silane |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
EP4006150A1 (en) | 2015-09-09 | 2022-06-01 | QIAGEN GmbH | Polymerase enzyme |
US10450598B2 (en) | 2015-09-11 | 2019-10-22 | Illumina, Inc. | Systems and methods for obtaining a droplet having a designated concentration of a substance-of-interest |
US11530439B2 (en) | 2015-09-25 | 2022-12-20 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
US11981955B2 (en) | 2015-09-25 | 2024-05-14 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
US10982261B2 (en) | 2015-09-25 | 2021-04-20 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
EP3831825A1 (en) | 2015-09-25 | 2021-06-09 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
EP3663290A1 (en) | 2015-09-25 | 2020-06-10 | Illumina Cambridge Limited | Polymethine compounds and their use as fluorescent labels |
US10465232B1 (en) | 2015-10-08 | 2019-11-05 | Trace Genomics, Inc. | Methods for quantifying efficiency of nucleic acid extraction and detection |
US10894981B2 (en) | 2015-10-13 | 2021-01-19 | Japan Agency For Marine-Earth Science And Technology | Method for fragmenting double-stranded RNA and use of the same |
US10253352B2 (en) | 2015-11-17 | 2019-04-09 | Omniome, Inc. | Methods for determining sequence profiles |
EP3798321A1 (en) | 2015-12-17 | 2021-03-31 | Illumina, Inc. | Distinguishing methylation levels in complex biological samples |
US11319593B2 (en) | 2015-12-17 | 2022-05-03 | Illumina, Inc. | Distinguishing methylation levels in complex biological samples |
DE202017100081U1 (en) | 2016-01-11 | 2017-03-19 | Illumina, Inc. | Detection device with a microfluorometer, a fluidic system and a flow cell detent module |
WO2017165703A1 (en) | 2016-03-24 | 2017-09-28 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
US10837057B2 (en) | 2016-03-24 | 2020-11-17 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
US11254983B2 (en) | 2016-03-24 | 2022-02-22 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
US10059992B2 (en) | 2016-03-24 | 2018-08-28 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
EP4053545A1 (en) | 2016-03-24 | 2022-09-07 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
US10472675B2 (en) | 2016-03-24 | 2019-11-12 | Illumina, Inc. | Photonic superlattice-based devices and compositions for use in luminescent imaging, and methods of using the same |
US10961568B2 (en) | 2016-03-28 | 2021-03-30 | Boreal Genomics, Inc. | Linked target capture |
EP3831484A1 (en) | 2016-03-28 | 2021-06-09 | Illumina, Inc. | Multi-plane microarrays |
WO2017168332A1 (en) | 2016-03-28 | 2017-10-05 | Boreal Genomics, Inc. | Linked duplex target capture |
US11905556B2 (en) | 2016-03-28 | 2024-02-20 | Ncan Genomics, Inc. | Linked target capture |
US10801059B2 (en) | 2016-03-28 | 2020-10-13 | Boreal Genomics, Inc. | Droplet-based linked-fragment sequencing |
US10961573B2 (en) | 2016-03-28 | 2021-03-30 | Boreal Genomics, Inc. | Linked duplex target capture |
US11021742B2 (en) | 2016-03-28 | 2021-06-01 | Boreal Genomics, Inc. | Linked-fragment sequencing |
EP4282974A2 (en) | 2016-03-28 | 2023-11-29 | Ncan Genomics, Inc. | Linked duplex target capture |
WO2017177017A1 (en) | 2016-04-07 | 2017-10-12 | Omniome, Inc. | Methods of quantifying target nucleic acids and identifying sequence variants |
US10988501B2 (en) | 2016-04-22 | 2021-04-27 | Mgi Tech Co., Ltd. | Reversibly blocked nucleoside analogues and their use |
CN109790196B (en) * | 2016-04-22 | 2022-09-27 | 深圳华大智造科技股份有限公司 | Reversibly blocked nucleoside analogs and uses thereof |
WO2017185026A1 (en) * | 2016-04-22 | 2017-10-26 | Complete Genomics, Inc. | Reversibly blocked nucleoside analogues and their use |
WO2017184997A1 (en) | 2016-04-22 | 2017-10-26 | Illumina, Inc. | Photonic stucture-based devices and compositions for use in luminescent imaging of multiple sites within a pixel, and methods of using the same |
EP4224219A2 (en) | 2016-04-22 | 2023-08-09 | Illumina Inc | Photonic stucture-based devices and compositions for use in luminescent imaging of multiple sites within a pixel, and methods of using the same |
CN109790196A (en) * | 2016-04-22 | 2019-05-21 | 考利达基因组股份有限公司 | Reversible closed nucleoside analog and application thereof |
US11579336B2 (en) | 2016-04-22 | 2023-02-14 | Illumina, Inc. | Photonic structure-based devices and compositions for use in luminescent imaging of multiple sites within a pixel, and methods of using the same |
WO2017197027A1 (en) | 2016-05-11 | 2017-11-16 | Illumina, Inc. | Polynucleotide enrichment and amplification using argonaute systems |
US11542544B2 (en) | 2016-05-11 | 2023-01-03 | Illumina, Inc. | Polynucleotide enrichment and amplification using CRISPR-Cas or Argonaute systems |
EP3656873A2 (en) | 2016-05-11 | 2020-05-27 | Illumina, Inc. | Polynucleotide enrichment and amplification using argonaute systems |
EP4269611A2 (en) | 2016-05-11 | 2023-11-01 | Illumina, Inc. | Polynucleotide enrichment and amplification using argonaute systems |
WO2017201198A1 (en) | 2016-05-18 | 2017-11-23 | Illumina, Inc. | Self assembled patterning using patterned hydrophobic surfaces |
WO2018018008A1 (en) | 2016-07-22 | 2018-01-25 | Oregon Health & Science University | Single cell whole genome libraries and combinatorial indexing methods of making thereof |
US11535883B2 (en) | 2016-07-22 | 2022-12-27 | Illumina, Inc. | Single cell whole genome libraries and combinatorial indexing methods of making thereof |
EP3904514A1 (en) | 2016-07-22 | 2021-11-03 | Oregon Health & Science University | Single cell whole genome libraries and combinatorial indexing methods of making thereof |
WO2018064116A1 (en) | 2016-09-28 | 2018-04-05 | Illumina, Inc. | Methods and systems for data compression |
WO2018060482A1 (en) | 2016-09-30 | 2018-04-05 | Illumina Cambridge Limited | New fluorescent dyes and their uses as biomarkers |
US11370920B2 (en) | 2016-09-30 | 2022-06-28 | Illumina Cambridge Limited | Fluorescent dyes and their uses as biomarkers |
EP3974425A1 (en) | 2016-09-30 | 2022-03-30 | Illumina Cambridge Limited | New fluorescent dyes and their uses as biomarkers |
US10844225B2 (en) | 2016-09-30 | 2020-11-24 | Illumina Cambridge Limited | Fluorescent dyes and their uses as biomarkers |
US10385214B2 (en) | 2016-09-30 | 2019-08-20 | Illumina Cambridge Limited | Fluorescent dyes and their uses as biomarkers |
EP3308860A1 (en) | 2016-10-14 | 2018-04-18 | Illumina, Inc. | Cartridge assembly |
US10343160B2 (en) | 2016-10-14 | 2019-07-09 | Illumina, Inc. | Cartridge assembly |
US11458469B2 (en) | 2016-10-14 | 2022-10-04 | Illumina, Inc. | Cartridge assembly |
WO2018075785A1 (en) | 2016-10-19 | 2018-04-26 | Illumina, Inc. | Methods for chemical ligation of nucleic acids |
WO2018093780A1 (en) | 2016-11-16 | 2018-05-24 | Illumina, Inc. | Validation methods and systems for sequence variant calls |
EP4148145A1 (en) | 2016-11-17 | 2023-03-15 | Spatial Transcriptomics AB | Method for spatial tagging and analysing nucleic acids in a biological specimen |
EP3916108A1 (en) | 2016-11-17 | 2021-12-01 | Spatial Transcriptomics AB | Method for spatial tagging and analysing nucleic acids in a biological specimen |
EP4421185A2 (en) | 2016-11-17 | 2024-08-28 | 10x Genomics Sweden AB | Method for spatial tagging and analysing nucleic acids in a biological specimen |
US11879151B2 (en) | 2016-12-09 | 2024-01-23 | Ncan Genomics, Inc. | Linked ligation |
US11268137B2 (en) | 2016-12-09 | 2022-03-08 | Boreal Genomics, Inc. | Linked ligation |
EP4119663A1 (en) | 2016-12-09 | 2023-01-18 | The Broad Institute, Inc. | Crispr effector system based diagnostics |
US10533211B2 (en) | 2016-12-22 | 2020-01-14 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
EP4257596A2 (en) | 2016-12-22 | 2023-10-11 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
WO2018119057A2 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Array including sequencing primer and non-sequencing entity |
US11932900B2 (en) | 2016-12-22 | 2024-03-19 | Illumina, Inc. | Arrays including a resin film and a patterned polymer layer |
US11512339B2 (en) | 2016-12-22 | 2022-11-29 | Illumina, Inc. | Arrays including a resin film and a patterned polymer layer |
WO2018114710A1 (en) | 2016-12-22 | 2018-06-28 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
US11371078B2 (en) | 2016-12-22 | 2022-06-28 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
US10907196B2 (en) | 2016-12-22 | 2021-02-02 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
WO2018119053A1 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Arrays including a resin film and a patterned polymer layer |
US10214768B2 (en) | 2016-12-22 | 2019-02-26 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
WO2018119063A1 (en) | 2016-12-22 | 2018-06-28 | Illumina, Inc. | Arrays with quality control tracers |
US11952619B2 (en) | 2016-12-22 | 2024-04-09 | Illumina, Inc. | Arrays with quality control tracers |
WO2018125759A1 (en) | 2016-12-30 | 2018-07-05 | Omniome, Inc. | Method and system employing distinguishable polymerases for detecting ternary complexes and identifying cognate nucleotides |
US10808277B2 (en) | 2017-01-05 | 2020-10-20 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
WO2018128777A1 (en) | 2017-01-05 | 2018-07-12 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
US11661627B2 (en) | 2017-01-05 | 2023-05-30 | Illumina, Inc. | Kinetic exclusion amplification of nucleic acid libraries |
WO2018129314A1 (en) | 2017-01-06 | 2018-07-12 | Illumina, Inc. | Phasing correction |
WO2018128544A1 (en) | 2017-01-06 | 2018-07-12 | Agendia N.V. | Biomarkers for selecting patient groups, and uses thereof. |
US11150179B2 (en) | 2017-01-06 | 2021-10-19 | Illumina, Inc. | Phasing correction |
WO2018132389A1 (en) | 2017-01-10 | 2018-07-19 | Omniome, Inc. | Polymerases engineered to reduce nucleotide-independent dna binding |
WO2018136416A1 (en) | 2017-01-17 | 2018-07-26 | Illumina, Inc. | Oncogenic splice variant determination |
US11761035B2 (en) | 2017-01-18 | 2023-09-19 | Illumina, Inc. | Methods and systems for generation and error-correction of unique molecular index sets with heterogeneous molecular lengths |
US10844429B2 (en) | 2017-01-18 | 2020-11-24 | Illumina, Inc. | Methods and systems for generation and error-correction of unique molecular index sets with heterogeneous molecular lengths |
WO2018136118A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Genotyping by polymerase binding |
WO2018136117A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Allele-specific capture of nucleic acids |
WO2018136487A1 (en) | 2017-01-20 | 2018-07-26 | Omniome, Inc. | Process for cognate nucleotide detection in a nucleic acid sequencing workflow |
WO2018144563A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials of non-closed shapes |
WO2018144567A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials in non-rectilinear layouts |
WO2018144574A1 (en) | 2017-02-01 | 2018-08-09 | Illumina, Inc. | System and method with fiducials having offset layouts |
WO2018148723A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from pyrococcus abyssi |
WO2018148724A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from pyrococcus furiosus |
WO2018148726A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from phage t4 |
WO2018148727A1 (en) | 2017-02-13 | 2018-08-16 | Qiagen Waltham Inc. | Polymerase enzyme from 9°n |
US11866741B2 (en) | 2017-02-13 | 2024-01-09 | IsoPlexis Corporation | Polymerase enzyme from 9°N |
WO2018152162A1 (en) | 2017-02-15 | 2018-08-23 | Omniome, Inc. | Distinguishing sequences by detecting polymerase dissociation |
WO2018151601A1 (en) | 2017-02-17 | 2018-08-23 | Stichting Vumc | Swarm intelligence-enhanced diagnosis and therapy selection for cancer using tumor- educated platelets |
US10920219B2 (en) | 2017-02-21 | 2021-02-16 | Illumina, Inc. | Tagmentation using immobilized transposomes with linkers |
WO2018156519A1 (en) | 2017-02-21 | 2018-08-30 | Illumina Inc. | Tagmentation using immobilized transposomes with linkers |
US11708573B2 (en) | 2017-02-21 | 2023-07-25 | Illumina, Inc. | Tagmentation using immobilized transposomes with linkers |
US11174515B2 (en) | 2017-03-15 | 2021-11-16 | The Broad Institute, Inc. | CRISPR effector system based diagnostics |
US11104937B2 (en) | 2017-03-15 | 2021-08-31 | The Broad Institute, Inc. | CRISPR effector system based diagnostics |
US11021740B2 (en) | 2017-03-15 | 2021-06-01 | The Broad Institute, Inc. | Devices for CRISPR effector system based diagnostics |
WO2018170340A1 (en) | 2017-03-15 | 2018-09-20 | The Broad Institute, Inc. | Crispr effector system based diagnostics for virus detection |
US11518993B2 (en) | 2017-03-20 | 2022-12-06 | Illumina, Inc. | Methods and compositions for preparing nucleic acid libraries |
WO2018175258A1 (en) | 2017-03-20 | 2018-09-27 | Illumina, Inc. | Methods and compositions for preparing nuclelic acid libraries |
EP4053294A1 (en) | 2017-03-24 | 2022-09-07 | Life Technologies Corporation | Polynucleotide adapters and methods of use thereof |
WO2018175798A1 (en) | 2017-03-24 | 2018-09-27 | Life Technologies Corporation | Polynucleotide adapters and methods of use thereof |
US11504711B2 (en) | 2017-04-04 | 2022-11-22 | Pacific Biosciences Of California, Inc. | Fluidic apparatus and methods useful for chemical and biological reactions |
US10737267B2 (en) | 2017-04-04 | 2020-08-11 | Omniome, Inc. | Fluidic apparatus and methods useful for chemical and biological reactions |
EP3913053A1 (en) | 2017-04-23 | 2021-11-24 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
EP3842545A1 (en) | 2017-04-23 | 2021-06-30 | Illumina, Inc. | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018197945A1 (en) | 2017-04-23 | 2018-11-01 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
EP3872187A1 (en) | 2017-04-23 | 2021-09-01 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200380A1 (en) | 2017-04-23 | 2018-11-01 | Illumina, Inc. | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200386A1 (en) | 2017-04-23 | 2018-11-01 | Illumina, Inc. | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018197950A1 (en) | 2017-04-23 | 2018-11-01 | Illumina Cambridge Limited | Compositions and methods for improving sample identification in indexed nucleic acid libraries |
WO2018200709A1 (en) | 2017-04-25 | 2018-11-01 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
EP3674417A1 (en) | 2017-04-25 | 2020-07-01 | Omniome, Inc. | Methods and apparatus that increase sequencing-by-binding efficiency |
WO2018204423A1 (en) | 2017-05-01 | 2018-11-08 | Illumina, Inc. | Optimal index sequences for multiplex massively parallel sequencing |
WO2018208699A1 (en) | 2017-05-08 | 2018-11-15 | Illumina, Inc. | Universal short adapters for indexing of polynucleotide samples |
WO2018226708A1 (en) | 2017-06-07 | 2018-12-13 | Oregon Health & Science University | Single cell whole genome libraries for methylation sequencing |
EP3981884A1 (en) | 2017-06-07 | 2022-04-13 | Oregon Health & Science University | Single cell whole genome libraries for methylation sequencing |
EP4293122A2 (en) | 2017-06-07 | 2023-12-20 | Oregon Health & Science University | Single cell whole genome libraries for methylation sequencing |
WO2018236631A1 (en) | 2017-06-20 | 2018-12-27 | Illumina, Inc. | Methods and compositions for addressing inefficiencies in amplification reactions |
US12071662B2 (en) | 2017-07-12 | 2024-08-27 | Illumina Cambridge Limited | Short pendant arm linkers for nucleotides in sequencing applications |
US10526648B2 (en) | 2017-07-12 | 2020-01-07 | Illumina Cambridge Limited | Short pendant arm linkers for nucleotides in sequencing applications |
US11655502B2 (en) | 2017-07-12 | 2023-05-23 | Illumina Cambridge Limited | Short pendant arm linkers for nucleotides in sequencing applications |
US11001888B2 (en) | 2017-07-12 | 2021-05-11 | Illumina Cambridge Limited | Short pendant arm linkers for nucleotides in sequencing applications |
WO2019018366A1 (en) | 2017-07-18 | 2019-01-24 | Omniome, Inc. | Method of chemically modifying plastic surfaces |
WO2019027767A1 (en) | 2017-07-31 | 2019-02-07 | Illumina Inc. | Sequencing system with multiplexed biological sample aggregation |
WO2019028047A1 (en) | 2017-08-01 | 2019-02-07 | Illumina, Inc | Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells |
US11352668B2 (en) | 2017-08-01 | 2022-06-07 | Illumina, Inc. | Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells |
EP4212628A1 (en) | 2017-08-01 | 2023-07-19 | MGI Tech Co., Ltd. | Nucleic acid sequencing method |
WO2019023951A1 (en) | 2017-08-01 | 2019-02-07 | 深圳华大智造科技有限公司 | Nucleic acid sequencing method |
US11649498B2 (en) | 2017-08-01 | 2023-05-16 | Illumina, Inc. | Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells |
WO2019028166A1 (en) | 2017-08-01 | 2019-02-07 | Illumina, Inc. | Hydrogel beads for nucleotide sequencing |
EP4289967A2 (en) | 2017-08-01 | 2023-12-13 | Illumina, Inc. | Spatial indexing of genetic material and library preparation using hydrogel beads and flow cells |
EP4209597A1 (en) | 2017-08-01 | 2023-07-12 | MGI Tech Co., Ltd. | Nucleic acid sequencing method |
US10858701B2 (en) | 2017-08-15 | 2020-12-08 | Omniome, Inc. | Scanning apparatus and method useful for detection of chemical and biological analytes |
US10501796B2 (en) | 2017-08-15 | 2019-12-10 | Omniome, Inc. | Scanning apparatus and methods useful for detection of chemical and biological analytes |
US10858703B2 (en) | 2017-08-15 | 2020-12-08 | Omniome, Inc. | Scanning apparatus and methods useful for detection of chemical and biological analytes |
WO2019035897A1 (en) | 2017-08-15 | 2019-02-21 | Omniome, Inc. | Scanning apparatus and methods useful for detection of chemical and biological analytes |
US11898198B2 (en) | 2017-09-15 | 2024-02-13 | Illumina, Inc. | Universal short adapters with variable length non-random unique molecular identifiers |
US11447818B2 (en) | 2017-09-15 | 2022-09-20 | Illumina, Inc. | Universal short adapters with variable length non-random unique molecular identifiers |
WO2019055715A1 (en) | 2017-09-15 | 2019-03-21 | Illumina, Inc. | Universal short adapters with variable length non-random unique molecular identifiers |
WO2019079166A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Deep learning-based techniques for training deep convolutional neural networks |
WO2019079182A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Semi-supervised learning for training an ensemble of deep convolutional neural networks |
WO2019079180A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Deep convolutional neural networks for variant classification |
WO2019079202A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Aberrant splicing detection using convolutional neural networks (cnns) |
WO2019079200A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Deep learning-based aberrant splicing detection |
US11390619B2 (en) | 2017-10-16 | 2022-07-19 | Illumina Cambridge Limited | Secondary amine-substituted coumarin compounds and their uses as fluorescent labels |
WO2019079198A1 (en) | 2017-10-16 | 2019-04-25 | Illumina, Inc. | Deep learning-based splice site classification |
EP4296899A2 (en) | 2017-10-16 | 2023-12-27 | Illumina, Inc. | Deep learning-based techniques for pre-training deep convolutional neural networks |
US11858923B2 (en) | 2017-10-16 | 2024-01-02 | Illumina Cambridge Limited | Secondary amine-substituted coumarin compounds and their uses as fluorescent labels |
WO2019136376A1 (en) | 2018-01-08 | 2019-07-11 | Illumina, Inc. | High-throughput sequencing with semiconductor-based detection |
WO2019136388A1 (en) | 2018-01-08 | 2019-07-11 | Illumina, Inc. | Systems and devices for high-throughput sequencing with semiconductor-based detection |
US11953464B2 (en) | 2018-01-08 | 2024-04-09 | Illumina, Inc. | Semiconductor-based biosensors for base calling |
EP3913358A1 (en) | 2018-01-08 | 2021-11-24 | Illumina Inc | High-throughput sequencing with semiconductor-based detection |
US11561196B2 (en) | 2018-01-08 | 2023-01-24 | Illumina, Inc. | Systems and devices for high-throughput sequencing with semiconductor-based detection |
EP3901833A1 (en) | 2018-01-15 | 2021-10-27 | Illumina, Inc. | Deep learning-based variant classifier |
US11705219B2 (en) | 2018-01-15 | 2023-07-18 | Illumina, Inc. | Deep learning-based variant classifier |
WO2019140402A1 (en) | 2018-01-15 | 2019-07-18 | Illumina, Inc. | Deep learning-based variant classifier |
WO2019148206A1 (en) | 2018-01-29 | 2019-08-01 | The Broad Institute, Inc. | Crispr effector system based diagnostics |
US11884971B2 (en) | 2018-02-06 | 2024-01-30 | Pacific Biosciences Of California, Inc. | Compositions and techniques for nucleic acid primer extension |
EP4253562A2 (en) | 2018-02-13 | 2023-10-04 | Illumina, Inc. | Dna sequencing using hydrogel beads |
WO2019160820A1 (en) | 2018-02-13 | 2019-08-22 | Illumina, Inc. | Dna sequencing using hydrogel beads |
US11180752B2 (en) | 2018-02-13 | 2021-11-23 | Illumina, Inc. | DNA sequencing using hydrogel beads |
EP4083225A1 (en) | 2018-02-13 | 2022-11-02 | Illumina, Inc. | Dna sequencing using hydrogel beads |
WO2019195225A1 (en) | 2018-04-02 | 2019-10-10 | Illumina, Inc. | Compositions and methods for making controls for sequence-based genetic testing |
WO2019200338A1 (en) | 2018-04-12 | 2019-10-17 | Illumina, Inc. | Variant classifier based on deep neural networks |
WO2019203986A1 (en) | 2018-04-19 | 2019-10-24 | Omniome, Inc. | Improving accuracy of base calls in nucleic acid sequencing methods |
US11359226B2 (en) | 2018-04-20 | 2022-06-14 | Illumina, Inc. | Contiguity particle formation and methods of use |
WO2019204229A1 (en) | 2018-04-20 | 2019-10-24 | Illumina, Inc. | Methods of encapsulating single cells, the encapsulated cells and uses thereof |
US11242557B2 (en) | 2018-04-26 | 2022-02-08 | Omniome, Inc. | Methods and compositions for stabilizing nucleic acid-nucleotide-polymerase complexes |
EP4234718A2 (en) | 2018-04-26 | 2023-08-30 | Pacific Biosciences Of California, Inc. | Methods and compositions for stabilizing nucleic acid-nucleotide-polymerase complexes |
US10400272B1 (en) | 2018-04-26 | 2019-09-03 | Omniome, Inc. | Methods and compositions for stabilizing nucleic acid-nucleotide-polymerase complexes |
WO2019209426A1 (en) | 2018-04-26 | 2019-10-31 | Omniome, Inc. | Methods and compositions for stabilizing nucleic acid-nucleotide-polymerase complexes |
WO2019222264A1 (en) | 2018-05-15 | 2019-11-21 | Illumina, Inc. | Compositions and methods for chemical cleavage and deprotection of surface-bound oligonucleotides |
US12084474B2 (en) | 2018-05-15 | 2024-09-10 | Illumina, Inc. | Compositions and methods for chemical cleavage and deprotection of surface-bound oligonucleotides |
EP4306532A2 (en) | 2018-05-15 | 2024-01-17 | Illumina, Inc. | Chemical cleavage and deprotection |
US11981891B2 (en) | 2018-05-17 | 2024-05-14 | Illumina, Inc. | High-throughput single-cell sequencing with reduced amplification bias |
WO2019227015A1 (en) | 2018-05-25 | 2019-11-28 | Illumina, Inc. | Circulating rna signatures specific to preeclampsia |
WO2019231568A1 (en) | 2018-05-31 | 2019-12-05 | Omniome, Inc. | Increased signal to noise in nucleic acid sequencing |
US11339428B2 (en) | 2018-05-31 | 2022-05-24 | Pacific Biosciences Of California, Inc. | Increased signal to noise in nucleic acid sequencing |
US11180794B2 (en) | 2018-05-31 | 2021-11-23 | Omniome, Inc. | Methods and compositions for capping nucleic acids |
EP4269618A2 (en) | 2018-06-04 | 2023-11-01 | Illumina, Inc. | Methods of making high-throughput single-cell transcriptome libraries |
US12073922B2 (en) | 2018-07-11 | 2024-08-27 | Illumina, Inc. | Deep learning-based framework for identifying sequence patterns that cause sequence-specific errors (SSEs) |
WO2020014280A1 (en) | 2018-07-11 | 2020-01-16 | Illumina, Inc. | DEEP LEARNING-BASED FRAMEWORK FOR IDENTIFYING SEQUENCE PATTERNS THAT CAUSE SEQUENCE-SPECIFIC ERRORS (SSEs) |
WO2020023362A1 (en) | 2018-07-24 | 2020-01-30 | Omniome, Inc. | Serial formation of ternary complex species |
US11421262B2 (en) | 2018-07-24 | 2022-08-23 | Pacific Biosciences Of California, Inc. | Serial formation of ternary complex species |
WO2020022891A2 (en) | 2018-07-26 | 2020-01-30 | Stichting Vumc | Biomarkers for atrial fibrillation |
WO2020036991A1 (en) | 2018-08-15 | 2020-02-20 | Illumina, Inc. | Compositions and methods for improving library enrichment |
US11845923B2 (en) | 2018-09-11 | 2023-12-19 | Singular Genomics Systems, Inc. | Modified Archaeal family B polymerases |
US11136565B2 (en) | 2018-09-11 | 2021-10-05 | Singular Genomics Systems, Inc. | Modified archaeal family B polymerases |
WO2020060811A1 (en) | 2018-09-17 | 2020-03-26 | Omniome, Inc. | Engineered polymerases for improved sequencing |
WO2020081122A1 (en) | 2018-10-15 | 2020-04-23 | Illumina, Inc. | Deep learning-based techniques for pre-training deep convolutional neural networks |
WO2020086843A1 (en) | 2018-10-26 | 2020-04-30 | Illumina, Inc. | Modulating polymer beads for dna processing |
US11999945B2 (en) | 2018-10-26 | 2024-06-04 | Illumina, Inc. | Modulating polymer beads for DNA processing |
US11085036B2 (en) | 2018-10-26 | 2021-08-10 | Illumina, Inc. | Modulating polymer beads for DNA processing |
US11560552B2 (en) | 2018-10-31 | 2023-01-24 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2020092830A1 (en) | 2018-10-31 | 2020-05-07 | Illumina, Inc. | Polymerases, compositions, and methods of use |
US11104888B2 (en) | 2018-10-31 | 2021-08-31 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2020093261A1 (en) | 2018-11-07 | 2020-05-14 | 深圳华大智造极创科技有限公司 | Method for sequencing polynucleotides |
EP4293126A2 (en) | 2018-11-30 | 2023-12-20 | Illumina, Inc. | Analysis of multiple analytes using a single assay |
WO2020112604A2 (en) | 2018-11-30 | 2020-06-04 | Illumina, Inc. | Analysis of multiple analytes using a single assay |
WO2020117653A1 (en) | 2018-12-04 | 2020-06-11 | Omniome, Inc. | Mixed-phase fluids for nucleic acid sequencing and other analytical assays |
US10710076B2 (en) | 2018-12-04 | 2020-07-14 | Omniome, Inc. | Mixed-phase fluids for nucleic acid sequencing and other analytical assays |
US11001816B2 (en) | 2018-12-05 | 2021-05-11 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2020114918A1 (en) | 2018-12-05 | 2020-06-11 | Illumina Cambridge Limited | Methods and compositions for cluster generation by bridge amplification |
WO2020117968A2 (en) | 2018-12-05 | 2020-06-11 | Illumina, Inc. | Polymerases, compositions, and methods of use |
US11634697B2 (en) | 2018-12-05 | 2023-04-25 | Illumina, Inc. | Polymerases, compositions, and methods of use |
GB201820341D0 (en) | 2018-12-13 | 2019-01-30 | 10X Genomics Inc | Method for transposase-mediated spatial tagging and analysing genomic DNA in a biological specimen |
GB201820300D0 (en) | 2018-12-13 | 2019-01-30 | 10X Genomics Inc | Method for spatial tagging and analysing genomic DNA in a biological specimen |
US11268091B2 (en) | 2018-12-13 | 2022-03-08 | Dna Script Sas | Direct oligonucleotide synthesis on cells and biomolecules |
US11993773B2 (en) | 2018-12-13 | 2024-05-28 | Dna Script Sas | Methods for extending polynucleotides |
WO2020120179A1 (en) | 2018-12-14 | 2020-06-18 | Illumina Cambridge Limited | Decreasing phasing with unlabeled nucleotides during sequencing |
WO2020126593A1 (en) | 2018-12-17 | 2020-06-25 | Illumina Cambridge Limited | Compositions for use in polyunucleotide sequencing |
WO2020126595A1 (en) | 2018-12-17 | 2020-06-25 | Illumina Cambridge Limited | Primer oligonucleotide for sequencing |
WO2020126602A1 (en) | 2018-12-18 | 2020-06-25 | Illumina Cambridge Limited | Methods and compositions for paired end sequencing using a single surface primer |
WO2020131759A1 (en) | 2018-12-19 | 2020-06-25 | Roche Diagnostics Gmbh | 3' protected nucleotides |
WO2020132103A1 (en) | 2018-12-19 | 2020-06-25 | Illumina, Inc. | Methods for improving polynucleotide cluster clonality priority |
WO2020132350A2 (en) | 2018-12-20 | 2020-06-25 | Omniome, Inc. | Temperature control for analysis of nucleic acids and other analytes |
US12077815B2 (en) | 2018-12-20 | 2024-09-03 | Pacific Biosciences Of California, Inc. | Temperature control for analysis of nucleic acids and other analytes |
US11041199B2 (en) | 2018-12-20 | 2021-06-22 | Omniome, Inc. | Temperature control for analysis of nucleic acids and other analytes |
WO2020136170A3 (en) * | 2018-12-26 | 2020-08-13 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3'-hydroxy blocking groups and their use in polynucleotide sequencing methods |
US11827931B2 (en) | 2018-12-26 | 2023-11-28 | Illumina Cambridge Limited | Methods of preparing growing polynucleotides using nucleotides with 3′ AOM blocking group |
US11293061B2 (en) | 2018-12-26 | 2022-04-05 | Illumina Cambridge Limited | Sequencing methods using nucleotides with 3′ AOM blocking group |
CN112638925A (en) * | 2018-12-26 | 2021-04-09 | 伊卢米纳剑桥有限公司 | Nucleosides and nucleotides having 3' -hydroxyl blocking groups and their use in polynucleotide sequencing methods |
WO2020136170A2 (en) | 2018-12-26 | 2020-07-02 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3'-hydroxy blocking groups |
RU2818762C2 (en) * | 2018-12-26 | 2024-05-06 | Иллюмина Кембридж Лимитед | Nucleosides and nucleotides with 3'-hydroxy blocking groups and their use in methods of sequencing polynucleotides |
US11473136B2 (en) | 2019-01-03 | 2022-10-18 | Ncan Genomics, Inc. | Linked target capture |
WO2020141464A1 (en) | 2019-01-03 | 2020-07-09 | Boreal Genomics, Inc. | Linked target capture |
WO2020144373A1 (en) | 2019-01-11 | 2020-07-16 | Illumina Cambridge Limited | Complex surface-bound transposome complexes |
US11306348B2 (en) | 2019-01-11 | 2022-04-19 | Illumina Cambridge Limited | Complex surface-bound transposome complexes |
US11685946B2 (en) | 2019-01-11 | 2023-06-27 | Illumina Cambridge Limited | Complex surface-bound transposome complexes |
US11359221B2 (en) | 2019-02-12 | 2022-06-14 | Dna Script Sas | Efficient product cleavage in template-free enzymatic synthesis of polynucleotides |
US11905541B2 (en) | 2019-02-12 | 2024-02-20 | Dna Script Sas | Efficient product cleavage in template-free enzymatic synthesis of polynucleotides |
WO2020167574A1 (en) | 2019-02-14 | 2020-08-20 | Omniome, Inc. | Mitigating adverse impacts of detection systems on nucleic acids and other biological analytes |
US11499189B2 (en) | 2019-02-14 | 2022-11-15 | Pacific Biosciences Of California, Inc. | Mitigating adverse impacts of detection systems on nucleic acids and other biological analytes |
US11680950B2 (en) | 2019-02-20 | 2023-06-20 | Pacific Biosciences Of California, Inc. | Scanning apparatus and methods for detecting chemical and biological analytes |
WO2020178162A1 (en) | 2019-03-01 | 2020-09-10 | Illumina Cambridge Limited | Exocyclic amine-substituted coumarin compounds and their uses as fluorescent labels |
WO2020180778A1 (en) | 2019-03-01 | 2020-09-10 | Illumina, Inc. | High-throughput single-nuclei and single-cell libraries and methods of making and of using |
WO2020178231A1 (en) | 2019-03-01 | 2020-09-10 | Illumina, Inc. | Multiplexed fluorescent detection of analytes |
WO2020178165A1 (en) | 2019-03-01 | 2020-09-10 | Illumina Cambridge Limited | Tertiary amine substituted coumarin compounds and their uses as fluorescent labels |
NL2023327B1 (en) | 2019-03-01 | 2020-09-17 | Illumina Inc | Multiplexed fluorescent detection of analytes |
US11884825B2 (en) | 2019-03-01 | 2024-01-30 | Illumina Cambridge Limited | Exocyclic amine substituted coumarin compounds and uses as fluorescent labels |
US11390753B2 (en) | 2019-03-01 | 2022-07-19 | Illumina Cambridge Limited | Exocyclic amine substituted coumarin compounds and uses as fluorescent labels |
WO2020191391A2 (en) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Artificial intelligence-based sequencing |
WO2020205296A1 (en) | 2019-03-21 | 2020-10-08 | Illumina, Inc. | Artificial intelligence-based generation of sequencing metadata |
NL2023314B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based quality scoring |
US11908548B2 (en) | 2019-03-21 | 2024-02-20 | Illumina, Inc. | Training data generation for artificial intelligence-based sequencing |
EP4276769A2 (en) | 2019-03-21 | 2023-11-15 | Illumina, Inc. | Training data generation for artificial intelligence-based sequencing |
WO2020191389A1 (en) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Training data generation for artificial intelligence-based sequencing |
US11676685B2 (en) | 2019-03-21 | 2023-06-13 | Illumina, Inc. | Artificial intelligence-based quality scoring |
NL2023310B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Training data generation for artificial intelligence-based sequencing |
NL2023316B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based sequencing |
US11961593B2 (en) | 2019-03-21 | 2024-04-16 | Illumina, Inc. | Artificial intelligence-based determination of analyte data for base calling |
NL2023311B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based generation of sequencing metadata |
WO2020191390A2 (en) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Artificial intelligence-based quality scoring |
WO2020191387A1 (en) | 2019-03-21 | 2020-09-24 | Illumina, Inc. | Artificial intelligence-based base calling |
NL2023312B1 (en) | 2019-03-21 | 2020-09-28 | Illumina Inc | Artificial intelligence-based base calling |
US11783917B2 (en) | 2019-03-21 | 2023-10-10 | Illumina, Inc. | Artificial intelligence-based base calling |
WO2020193765A1 (en) | 2019-03-28 | 2020-10-01 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing using photoswitchable labels |
US11421271B2 (en) | 2019-03-28 | 2022-08-23 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing using photoswitchable labels |
US11959138B2 (en) | 2019-03-28 | 2024-04-16 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing using photoswitchable labels |
WO2020227953A1 (en) | 2019-05-15 | 2020-11-19 | 深圳华大智造极创科技有限公司 | Single-channel sequencing method based on self-luminescence |
WO2020232410A1 (en) | 2019-05-16 | 2020-11-19 | Illumina, Inc. | Base calling using convolutions |
US11593649B2 (en) | 2019-05-16 | 2023-02-28 | Illumina, Inc. | Base calling using convolutions |
US11817182B2 (en) | 2019-05-16 | 2023-11-14 | Illumina, Inc. | Base calling using three-dimentional (3D) convolution |
WO2020252186A1 (en) | 2019-06-11 | 2020-12-17 | Omniome, Inc. | Calibrated focus sensing |
WO2021009494A1 (en) | 2019-07-12 | 2021-01-21 | Illumina Cambridge Limited | Nucleic acid library preparation using electrophoresis |
WO2021008805A1 (en) | 2019-07-12 | 2021-01-21 | Illumina Cambridge Limited | Compositions and methods for preparing nucleic acid sequencing libraries using crispr/cas9 immobilized on a solid support |
US11377655B2 (en) | 2019-07-16 | 2022-07-05 | Pacific Biosciences Of California, Inc. | Synthetic nucleic acids having non-natural structures |
US10656368B1 (en) | 2019-07-24 | 2020-05-19 | Omniome, Inc. | Method and system for biological imaging using a wide field objective lens |
WO2021015838A1 (en) | 2019-07-24 | 2021-01-28 | Omniome, Inc. | Objective lens of a microscope for imaging an array of nucleic acids and system for dna sequencing |
US11644636B2 (en) | 2019-07-24 | 2023-05-09 | Pacific Biosciences Of California, Inc. | Method and system for biological imaging using a wide field objective lens |
WO2021031109A1 (en) | 2019-08-20 | 2021-02-25 | 深圳华大智造极创科技有限公司 | Method for sequencing polynucleotides on basis of optical signal dynamics of luminescent label and secondary luminescent signal |
US12098419B2 (en) | 2019-08-23 | 2024-09-24 | Ncan Genomics, Inc. | Linked target capture and ligation |
EP4265628A2 (en) | 2019-09-10 | 2023-10-25 | Pacific Biosciences of California, Inc. | Reversible modification of nucleotides |
WO2021050681A1 (en) | 2019-09-10 | 2021-03-18 | Omniome, Inc. | Reversible modification of nucleotides |
US11180520B2 (en) | 2019-09-10 | 2021-11-23 | Omniome, Inc. | Reversible modifications of nucleotides |
WO2021050962A1 (en) | 2019-09-11 | 2021-03-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cancer detection and classification |
US11512295B2 (en) | 2019-09-12 | 2022-11-29 | Singular Genomics Systems, Inc. | Modified thermoccocus polymerases |
WO2021076152A1 (en) | 2019-10-18 | 2021-04-22 | Omniome, Inc. | Methods and compositions for capping nucleic acids |
WO2021092431A1 (en) | 2019-11-08 | 2021-05-14 | Omniome, Inc. | Engineered polymerases for improved sequencing by binding |
WO2021102236A1 (en) | 2019-11-22 | 2021-05-27 | Illumina, Inc. | Circulating rna signatures specific to preeclampsia |
WO2021104845A1 (en) | 2019-11-27 | 2021-06-03 | Illumina Cambridge Limited | Cyclooctatetraene containing dyes and compositions |
US11597969B2 (en) | 2019-11-27 | 2023-03-07 | Illumina Cambridge Limited | Cyclooctatetraene containing dyes and compositions |
US12031178B2 (en) | 2019-11-27 | 2024-07-09 | Illumina Cambridge Limited | Cyclooctatetraene containing dyes and compositions |
DE202019106695U1 (en) | 2019-12-02 | 2020-03-19 | Omniome, Inc. | System for sequencing nucleic acids in fluid foam |
DE202019106694U1 (en) | 2019-12-02 | 2020-03-19 | Omniome, Inc. | System for sequencing nucleic acids in fluid foam |
WO2021113287A1 (en) | 2019-12-04 | 2021-06-10 | Illumina, Inc. | Preparation of dna sequencing libraries for detection of dna pathogens in plasma |
WO2021118349A1 (en) | 2019-12-10 | 2021-06-17 | Prinses Máxima Centrum Voor Kinderoncologie B.V. | Methods of typing germ cell tumors |
WO2021123074A1 (en) | 2019-12-18 | 2021-06-24 | F. Hoffmann-La Roche Ag | Methods of sequencing by synthesis using a consecutive labeling scheme |
WO2021127436A2 (en) | 2019-12-19 | 2021-06-24 | Illumina, Inc. | High-throughput single-cell libraries and methods of making and of using |
US11225688B2 (en) | 2019-12-23 | 2022-01-18 | Singular Genomics Systems, Inc. | Methods for long read sequencing |
US11747262B2 (en) | 2019-12-23 | 2023-09-05 | Singular Genomics Systems, Inc. | Flow cell carrier and methods of use |
WO2021133685A1 (en) | 2019-12-23 | 2021-07-01 | Singular Genomics Systems, Inc. | Methods for long read sequencing |
US11498078B2 (en) | 2019-12-23 | 2022-11-15 | Singular Genomics Systems, Inc. | Flow cell receiver and methods of use |
US11813615B2 (en) | 2019-12-23 | 2023-11-14 | Singular Genomics Systems, Inc. | Flow cell receiver and devices |
US12066370B2 (en) | 2019-12-23 | 2024-08-20 | Singular Genomics Systems, Inc. | Flow cell carrier device |
WO2021138094A1 (en) | 2019-12-31 | 2021-07-08 | Singular Genomics Systems, Inc. | Polynucleotide barcodes for long read sequencing |
US11155858B2 (en) | 2019-12-31 | 2021-10-26 | Singular Genomics Systems, Inc. | Polynucleotide barcodes for long read sequencing |
WO2021158511A1 (en) | 2020-02-04 | 2021-08-12 | Omniome, Inc. | Flow cells and methods for their manufacture and use |
WO2021168014A1 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Knowledge distillation and gradient pruning-based compression of artificial intelligence-based base caller |
WO2021168353A2 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Artificial intelligence-based many-to-many base calling |
US11749380B2 (en) | 2020-02-20 | 2023-09-05 | Illumina, Inc. | Artificial intelligence-based many-to-many base calling |
WO2021168018A1 (en) | 2020-02-20 | 2021-08-26 | Illumina, Inc. | Hardware execution and acceleration of artificial intelligence-based base caller |
US11891633B2 (en) | 2020-02-27 | 2024-02-06 | Singular Genomics Systems, Inc. | Modified pyrococcus polymerases and uses thereof |
US11851687B2 (en) | 2020-02-27 | 2023-12-26 | Singular Genomics Systems, Inc. | Modified Pyrococcus polymerases and uses thereof |
US11034942B1 (en) | 2020-02-27 | 2021-06-15 | Singular Genomics Systems, Inc. | Modified pyrococcus polymerases and uses thereof |
US11884943B2 (en) | 2020-02-27 | 2024-01-30 | Singular Genomics Systems, Inc. | Engineered Pyrococcus enzymes and uses thereof |
WO2021178467A1 (en) | 2020-03-03 | 2021-09-10 | Omniome, Inc. | Methods and compositions for sequencing double stranded nucleic acids |
US11608528B2 (en) | 2020-03-03 | 2023-03-21 | Pacific Biosciences Of California, Inc. | Methods and compositions for sequencing double stranded nucleic acids using RCA and MDA |
US12077816B2 (en) | 2020-03-06 | 2024-09-03 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
US11359238B2 (en) | 2020-03-06 | 2022-06-14 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
US11891660B2 (en) | 2020-03-06 | 2024-02-06 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
US11365445B2 (en) | 2020-03-06 | 2022-06-21 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
US11519029B2 (en) | 2020-03-06 | 2022-12-06 | Singular Genomics Systems, Inc. | Linked paired strand sequencing |
WO2021180733A1 (en) | 2020-03-09 | 2021-09-16 | Illumina, Inc. | Methods for sequencing polynucleotides |
EP4421187A2 (en) | 2020-03-30 | 2024-08-28 | Illumina, Inc. | Methods and compositions for preparing nucleic acid libraries |
WO2021202403A1 (en) | 2020-03-30 | 2021-10-07 | Illumina, Inc. | Methods and compositions for preparing nucleic acid libraries |
WO2021221500A1 (en) | 2020-04-27 | 2021-11-04 | Agendia N.V. | Treatment of her2 negative, mammaprint high risk 2 breast cancer. |
WO2021225886A1 (en) | 2020-05-05 | 2021-11-11 | Omniome, Inc. | Compositions and methods for modifying polymerase-nucleic acid complexes |
WO2021226285A1 (en) | 2020-05-05 | 2021-11-11 | Illumina, Inc. | Equalization-based image processing and spatial crosstalk attenuator |
US11694309B2 (en) | 2020-05-05 | 2023-07-04 | Illumina, Inc. | Equalizer-based intensity correction for base calling |
WO2021231477A2 (en) | 2020-05-12 | 2021-11-18 | Illumina, Inc. | Generating nucleic acids with modified bases using recombinant terminal deoxynucleotidyl transferase |
WO2021252617A1 (en) | 2020-06-09 | 2021-12-16 | Illumina, Inc. | Methods for increasing yield of sequencing libraries |
WO2021252800A1 (en) | 2020-06-11 | 2021-12-16 | Nautilus Biotechnology, Inc. | Methods and systems for computational decoding of biological, chemical, and physical entities |
US11935311B2 (en) | 2020-06-11 | 2024-03-19 | Nautilus Subsidiary, Inc. | Methods and systems for computational decoding of biological, chemical, and physical entities |
EP4231174A2 (en) | 2020-06-11 | 2023-08-23 | Nautilus Subsidiary, Inc. | Methods and systems for computational decoding of biological, chemical, and physical entities |
US11787831B2 (en) | 2020-06-22 | 2023-10-17 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3′ acetal blocking group |
CN115867560A (en) * | 2020-06-22 | 2023-03-28 | 伊鲁米纳剑桥有限公司 | Nucleosides and nucleotides having 3' acetal capping groups |
US20210403500A1 (en) * | 2020-06-22 | 2021-12-30 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3' acetal blocking group |
WO2021259881A1 (en) | 2020-06-22 | 2021-12-30 | Illumina Cambridge Limited | Nucleosides and nucleotides with 3' acetal blocking group |
WO2022006081A1 (en) | 2020-06-30 | 2022-01-06 | Illumina, Inc. | Catalytically controlled sequencing by synthesis to produce scarless dna |
WO2022006495A1 (en) | 2020-07-02 | 2022-01-06 | Illumina, Inc. | A method to calibrate nucleic acid library seeding efficiency in flowcells |
WO2022010965A1 (en) | 2020-07-08 | 2022-01-13 | Illumina, Inc. | Beads as transposome carriers |
US11486004B2 (en) | 2020-07-13 | 2022-11-01 | Singular Genomics Systems, Inc. | Methods of sequencing circular template polynucleotides |
US11993801B2 (en) | 2020-07-21 | 2024-05-28 | Illumina Singapore Pte. Ltd. | Base-modified nucleotides as substrates for TdT-based enzymatic nucleic acid synthesis |
US11981964B2 (en) | 2020-07-28 | 2024-05-14 | Illumina Cambridge Limited | Substituted coumarin dyes and uses as fluorescent labels |
WO2022023353A1 (en) | 2020-07-28 | 2022-02-03 | Illumina Cambridge Limited | Substituted coumarin dyes and uses as fluorescent labels |
WO2022031955A1 (en) | 2020-08-06 | 2022-02-10 | Illumina, Inc. | Preparation of rna and dna sequencing libraries using bead-linked transposomes |
WO2022040176A1 (en) | 2020-08-18 | 2022-02-24 | Illumina, Inc. | Sequence-specific targeted transposition and selection and sorting of nucleic acids |
WO2022053610A1 (en) | 2020-09-11 | 2022-03-17 | Illumina Cambridge Limited | Methods of enriching a target sequence from a sequencing library using hairpin adaptors |
WO2022087150A2 (en) | 2020-10-21 | 2022-04-28 | Illumina, Inc. | Sequencing templates comprising multiple inserts and compositions and methods for improving sequencing throughput |
US12071665B2 (en) | 2020-10-22 | 2024-08-27 | Singular Genomics Systems, Inc. | Nucleic acid circularization and amplification on a surface |
US12031179B2 (en) | 2020-10-30 | 2024-07-09 | Singular Genomics Systems, Inc. | Methods and compositions for reducing nucleotide impurities |
US11781185B2 (en) | 2020-10-30 | 2023-10-10 | Element Biosciences, Inc. | Methods and reagents for nucleic acid analysis |
WO2022103499A1 (en) | 2020-11-11 | 2022-05-19 | Microsoft Technology Licensing, Llc | Spatial control of polynucleotide synthesis by strand capping |
WO2022109269A3 (en) * | 2020-11-20 | 2022-06-30 | The General Hospital Corporation | Methods for dna methylation analysis |
WO2022129437A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Long stokes shift chromenoquinoline dyes and uses in sequencing applications |
WO2022129930A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Alkylpyridinium coumarin dyes and uses in sequencing applications |
WO2022129439A1 (en) | 2020-12-17 | 2022-06-23 | Illumina Cambridge Limited | Methods, systems and compositions for nucleic acid sequencing |
WO2022140291A1 (en) | 2020-12-21 | 2022-06-30 | Singular Genomics Systems, Inc. | Systems and methods for multicolor imaging |
US11415515B2 (en) | 2020-12-21 | 2022-08-16 | Singular Genomics Systems, Inc. | Systems and methods for multicolor imaging |
US11686681B2 (en) | 2020-12-21 | 2023-06-27 | Singular Genomics Systems, Inc. | Systems and methods for multicolor imaging |
WO2022136402A1 (en) | 2020-12-22 | 2022-06-30 | Illumina Cambridge Limited | Methods and compositions for nucleic acid sequencing |
WO2022155331A1 (en) | 2021-01-13 | 2022-07-21 | Pacific Biosciences Of California, Inc. | Surface structuring with colloidal assembly |
WO2022165188A1 (en) | 2021-01-29 | 2022-08-04 | Illumina, Inc. | Methods, compositions and kits to improve seeding efficiency of flow cells with polynucleotides |
WO2022169972A1 (en) | 2021-02-04 | 2022-08-11 | Illumina, Inc. | Long indexed-linked read generation on transposome bound beads |
US11913071B2 (en) | 2021-02-08 | 2024-02-27 | Singular Genomics Systems, Inc. | Methods and compositions for sequencing complementary polynucleotides |
US11788133B2 (en) | 2021-02-08 | 2023-10-17 | Singular Genomics Systems, Inc. | Methods and compositions for sequencing complementary polynucleotides |
US11486001B2 (en) | 2021-02-08 | 2022-11-01 | Singular Genomics Systems, Inc. | Methods and compositions for sequencing complementary polynucleotides |
US11560590B2 (en) | 2021-02-08 | 2023-01-24 | Singular Genomics Systems, Inc. | Methods and compositions for sequencing complementary polynucleotides |
WO2022174054A1 (en) | 2021-02-13 | 2022-08-18 | The General Hospital Corporation | Methods and compositions for in situ macromolecule detection and uses thereof |
US11884977B2 (en) | 2021-03-12 | 2024-01-30 | Singular Genomics Systems, Inc. | Nanoarrays and methods of use thereof |
US11629380B2 (en) | 2021-03-12 | 2023-04-18 | Singular Genomics Systems, Inc. | Nanoarrays and methods of use thereof |
WO2022197752A1 (en) | 2021-03-16 | 2022-09-22 | Illumina, Inc. | Tile location and/or cycle based weight set selection for base calling |
WO2022204032A1 (en) | 2021-03-22 | 2022-09-29 | Illumina Cambridge Limited | Methods for improving nucleic acid cluster clonality |
WO2022212269A1 (en) | 2021-03-29 | 2022-10-06 | Illumina, Inc. | Improved methods of library preparation |
WO2022212280A1 (en) | 2021-03-29 | 2022-10-06 | Illumina, Inc. | Compositions and methods for assessing dna damage in a library and normalizing amplicon size bias |
WO2022212330A1 (en) | 2021-03-30 | 2022-10-06 | Illumina, Inc. | Improved methods of isothermal complementary dna and library preparation |
WO2022212402A1 (en) | 2021-03-31 | 2022-10-06 | Illumina, Inc. | Methods of preparing directional tagmentation sequencing libraries using transposon-based technology with unique molecular identifiers for error correction |
WO2022213027A1 (en) | 2021-04-02 | 2022-10-06 | Illumina, Inc. | Machine-learning model for detecting a bubble within a nucleotide-sample slide for sequencing |
US11515010B2 (en) | 2021-04-15 | 2022-11-29 | Illumina, Inc. | Deep convolutional neural networks to predict variant pathogenicity using three-dimensional (3D) protein structures |
US12070744B2 (en) | 2021-04-22 | 2024-08-27 | Illumina, Inc. | Valve assemblies and related systems |
US11578320B2 (en) | 2021-04-27 | 2023-02-14 | Singular Genomics Systems, Inc. | High density sequencing and multiplexed priming |
US11649452B2 (en) | 2021-04-27 | 2023-05-16 | Singular Genomics Systems, Inc. | High density sequencing and multiplexed priming |
WO2022233795A1 (en) | 2021-05-05 | 2022-11-10 | Illumina Cambridge Limited | Fluorescent dyes containing bis-boron fused heterocycles and uses in sequencing |
WO2022235163A1 (en) | 2021-05-07 | 2022-11-10 | Agendia N.V. | Endocrine treatment of hormone receptor positive breast cancer typed as having a low risk of recurrence |
WO2022240764A1 (en) | 2021-05-10 | 2022-11-17 | Pacific Biosciences Of California, Inc. | Single-molecule seeding and amplification on a surface |
WO2022240766A1 (en) | 2021-05-10 | 2022-11-17 | Pacific Biosciences Of California, Inc. | Dna amplification buffer replenishment during rolling circle amplification |
WO2022243480A1 (en) | 2021-05-20 | 2022-11-24 | Illumina, Inc. | Compositions and methods for sequencing by synthesis |
WO2022265994A1 (en) | 2021-06-15 | 2022-12-22 | Illumina, Inc. | Hydrogel-free surface functionalization for sequencing |
WO2023278184A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Methods and systems to correct crosstalk in illumination emitted from reaction sites |
WO2023278966A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Machine-learning model for generating confidence classifications for genomic coordinates |
WO2023278609A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Self-learned base caller, trained using organism sequences |
WO2023278927A1 (en) | 2021-06-29 | 2023-01-05 | Illumina Software, Inc. | Signal-to-noise-ratio metric for determining nucleotide-base calls and base-call quality |
WO2023278608A1 (en) | 2021-06-29 | 2023-01-05 | Illumina, Inc. | Self-learned base caller, trained using oligo sequences |
WO2023287617A1 (en) | 2021-07-13 | 2023-01-19 | Illumina, Inc. | Methods and systems for real time extraction of crosstalk in illumination emitted from reaction sites |
WO2023003757A1 (en) | 2021-07-19 | 2023-01-26 | Illumina Software, Inc. | Intensity extraction with interpolation and adaptation for base calling |
US11989265B2 (en) | 2021-07-19 | 2024-05-21 | Illumina, Inc. | Intensity extraction from oligonucleotide clusters for base calling |
WO2023004357A1 (en) | 2021-07-23 | 2023-01-26 | Illumina, Inc. | Methods for preparing substrate surface for dna sequencing |
WO2023004323A1 (en) | 2021-07-23 | 2023-01-26 | Illumina Software, Inc. | Machine-learning model for recalibrating nucleotide-base calls |
WO2023009758A1 (en) | 2021-07-28 | 2023-02-02 | Illumina, Inc. | Quality score calibration of basecalling systems |
WO2023014741A1 (en) | 2021-08-03 | 2023-02-09 | Illumina Software, Inc. | Base calling using multiple base caller models |
WO2023020728A1 (en) | 2021-08-14 | 2023-02-23 | Illumina, Inc. | Polymerases, compositions, and methods of use |
US12077789B2 (en) | 2021-08-14 | 2024-09-03 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2023023500A1 (en) | 2021-08-17 | 2023-02-23 | Illumina, Inc. | Methods and compositions for identifying methylated cytosines |
US11932905B2 (en) | 2021-09-03 | 2024-03-19 | Singular Genomics Systems, Inc. | Amplification oligonucleotides |
US11802307B2 (en) | 2021-09-03 | 2023-10-31 | Singular Genomics Systems, Inc. | Amplification oligonucleotides |
US11859244B2 (en) | 2021-09-03 | 2024-01-02 | Singular Genomics Systems, Inc. | Amplification oligonucleotides |
WO2023035110A1 (en) | 2021-09-07 | 2023-03-16 | 深圳华大智造科技股份有限公司 | Method for analyzing sequence of target polynucleotide |
WO2023035108A1 (en) | 2021-09-07 | 2023-03-16 | 深圳华大智造科技股份有限公司 | Method for analyzing sequence of target polynucleotide |
WO2023044229A1 (en) | 2021-09-17 | 2023-03-23 | Illumina, Inc. | Automatically identifying failure sources in nucleotide sequencing from base-call-error patterns |
WO2023049558A1 (en) | 2021-09-21 | 2023-03-30 | Illumina, Inc. | A graph reference genome and base-calling approach using imputed haplotypes |
WO2023049215A1 (en) | 2021-09-22 | 2023-03-30 | Illumina, Inc. | Compressed state-based base calling |
WO2023049212A2 (en) | 2021-09-22 | 2023-03-30 | Illumina, Inc. | State-based base calling |
WO2023056328A2 (en) | 2021-09-30 | 2023-04-06 | Illumina, Inc. | Solid supports and methods for depleting and/or enriching library fragments prepared from biosamples |
WO2023052427A1 (en) | 2021-09-30 | 2023-04-06 | Illumina Cambridge Limited | Polynucleotide sequencing |
WO2023069927A1 (en) | 2021-10-20 | 2023-04-27 | Illumina, Inc. | Methods for capturing library dna for sequencing |
US11455487B1 (en) | 2021-10-26 | 2022-09-27 | Illumina Software, Inc. | Intensity extraction and crosstalk attenuation using interpolation and adaptation for base calling |
WO2023081485A1 (en) | 2021-11-08 | 2023-05-11 | Pacific Biosciences Of California, Inc. | Stepwise sequencing of a polynucleotide with a homogenous reaction mixture |
WO2023085932A1 (en) | 2021-11-10 | 2023-05-19 | Omnigen B.V. | Prediction of response following folfirinox treatment in cancer patients |
WO2023102354A1 (en) | 2021-12-02 | 2023-06-08 | Illumina Software, Inc. | Generating cluster-specific-signal corrections for determining nucleotide-base calls |
US12099178B2 (en) | 2021-12-16 | 2024-09-24 | Singular Genomics Systems, Inc. | Kinematic imaging system |
WO2023122362A1 (en) | 2021-12-23 | 2023-06-29 | Illumina Software, Inc. | Facilitating secure execution of external workflows for genomic sequencing diagnostics |
WO2023122363A1 (en) | 2021-12-23 | 2023-06-29 | Illumina Software, Inc. | Dynamic graphical status summaries for nucelotide sequencing |
WO2023129896A1 (en) | 2021-12-28 | 2023-07-06 | Illumina Software, Inc. | Machine learning model for recalibrating nucleotide base calls corresponding to target variants |
WO2023126457A1 (en) | 2021-12-29 | 2023-07-06 | Illumina Cambridge Ltd. | Methods of nucleic acid sequencing using surface-bound primers |
WO2023129764A1 (en) | 2021-12-29 | 2023-07-06 | Illumina Software, Inc. | Automatically switching variant analysis model versions for genomic analysis applications |
WO2023141154A1 (en) | 2022-01-20 | 2023-07-27 | Illumina Cambridge Limited | Methods of detecting methylcytosine and hydroxymethylcytosine by sequencing |
WO2023164660A1 (en) | 2022-02-25 | 2023-08-31 | Illumina, Inc. | Calibration sequences for nucelotide sequencing |
WO2023164492A1 (en) | 2022-02-25 | 2023-08-31 | Illumina, Inc. | Machine-learning models for detecting and adjusting values for nucleotide methylation levels |
US11795505B2 (en) | 2022-03-10 | 2023-10-24 | Singular Genomics Systems, Inc. | Nucleic acid delivery scaffolds |
WO2023183937A1 (en) | 2022-03-25 | 2023-09-28 | Illumina, Inc. | Sequence-to-sequence base calling |
WO2023186815A1 (en) | 2022-03-28 | 2023-10-05 | Illumina Cambridge Limited | Labeled avidin and methods for sequencing |
WO2023186819A1 (en) | 2022-03-29 | 2023-10-05 | Illumina Cambridge Limited | Chromenoquinoline dyes and uses in sequencing |
WO2023192917A1 (en) | 2022-03-29 | 2023-10-05 | Nautilus Subsidiary, Inc. | Integrated arrays for single-analyte processes |
WO2023192163A1 (en) | 2022-03-29 | 2023-10-05 | Illumina Cambridge Limited | Systems and methods of sequencing polynucleotides |
WO2023186982A1 (en) | 2022-03-31 | 2023-10-05 | Illumina, Inc. | Compositions and methods for improving sequencing signals |
WO2023192900A1 (en) | 2022-03-31 | 2023-10-05 | Illumina Singapore Pte. Ltd. | Nucleosides and nucleotides with 3' vinyl blocking group useful in sequencing by synthesis |
WO2023196572A1 (en) | 2022-04-07 | 2023-10-12 | Illumina Singapore Pte. Ltd. | Altered cytidine deaminases and methods of use |
WO2023212601A1 (en) | 2022-04-26 | 2023-11-02 | Illumina, Inc. | Machine-learning models for selecting oligonucleotide probes for array technologies |
WO2023220627A1 (en) | 2022-05-10 | 2023-11-16 | Illumina Software, Inc. | Adaptive neural network for nucelotide sequencing |
WO2023224487A1 (en) | 2022-05-19 | 2023-11-23 | Agendia N.V. | Prediction of response to immune therapy in breast cancer patients |
WO2023224488A1 (en) | 2022-05-19 | 2023-11-23 | Agendia N.V. | Dna repair signature and prediction of response following cancer therapy |
WO2023232829A1 (en) | 2022-05-31 | 2023-12-07 | Illumina, Inc | Compositions and methods for nucleic acid sequencing |
WO2023235353A2 (en) | 2022-06-03 | 2023-12-07 | Illumina, Inc. | Circulating rna biomarkers for preeclampsia |
WO2023239917A1 (en) | 2022-06-09 | 2023-12-14 | Illumina, Inc. | Dependence of base calling on flow cell tilt |
WO2023250504A1 (en) | 2022-06-24 | 2023-12-28 | Illumina Software, Inc. | Improving split-read alignment by intelligently identifying and scoring candidate split groups |
WO2024006769A1 (en) | 2022-06-27 | 2024-01-04 | Illumina Software, Inc. | Generating and implementing a structural variation graph genome |
WO2024006779A1 (en) | 2022-06-27 | 2024-01-04 | Illumina, Inc. | Accelerators for a genotype imputation model |
WO2024006705A1 (en) | 2022-06-27 | 2024-01-04 | Illumina Software, Inc. | Improved human leukocyte antigen (hla) genotyping |
WO2024003087A1 (en) | 2022-06-28 | 2024-01-04 | Illumina, Inc. | Fluorescent dyes containing fused tetracyclic bis-boron heterocycle and uses in sequencing |
WO2024015962A1 (en) | 2022-07-15 | 2024-01-18 | Pacific Biosciences Of California, Inc. | Blocked asymmetric hairpin adaptors |
WO2024026356A1 (en) | 2022-07-26 | 2024-02-01 | Illumina, Inc. | Rapid single-cell multiomics processing using an executable file |
CN115260262A (en) * | 2022-08-09 | 2022-11-01 | 深圳赛陆医疗科技有限公司 | Preparation method of cytosine azide |
CN115260262B (en) * | 2022-08-09 | 2024-09-27 | 深圳赛陆医疗科技有限公司 | Cytosine azide Process for the preparation of compounds |
WO2024039516A1 (en) | 2022-08-19 | 2024-02-22 | Illumina, Inc. | Third dna base pair site-specific dna detection |
WO2024059852A1 (en) | 2022-09-16 | 2024-03-21 | Illumina, Inc. | Cluster segmentation and conditional base calling |
WO2024073516A1 (en) | 2022-09-29 | 2024-04-04 | Illumina, Inc. | A target-variant-reference panel for imputing target variants |
WO2024073043A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Methods of using cpg binding proteins in mapping modified cytosine nucleotides |
WO2024073519A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Machine-learning model for refining structural variant calls |
WO2024068971A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Polymerases, compositions, and methods of use |
WO2024073047A1 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Cytidine deaminases and methods of use in mapping modified cytosine nucleotides |
WO2024069581A1 (en) | 2022-09-30 | 2024-04-04 | Illumina Singapore Pte. Ltd. | Helicase-cytidine deaminase complexes and methods of use |
WO2024068889A2 (en) | 2022-09-30 | 2024-04-04 | Illumina, Inc. | Compositions and methods for reducing photo damage during sequencing |
WO2024077096A1 (en) | 2022-10-05 | 2024-04-11 | Illumina, Inc. | Integrating variant calls from multiple sequencing pipelines utilizing a machine learning architecture |
WO2024077162A2 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for improving coronavirus sample surveillance |
WO2024077202A2 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for improving environmental sample surveillance |
WO2024077152A1 (en) | 2022-10-06 | 2024-04-11 | Illumina, Inc. | Probes for depleting abundant small noncoding rna |
WO2024081649A1 (en) | 2022-10-11 | 2024-04-18 | Illumina, Inc. | Detecting and correcting methylation values from methylation sequencing assays |
WO2024118903A1 (en) | 2022-11-30 | 2024-06-06 | Illumina, Inc. | Chemoenzymatic correction of false positive uracil transformations |
WO2024118791A1 (en) | 2022-11-30 | 2024-06-06 | Illumina, Inc. | Accurately predicting variants from methylation sequencing data |
WO2024123866A1 (en) | 2022-12-09 | 2024-06-13 | Illumina, Inc. | Nucleosides and nucleotides with 3´ blocking groups and cleavable linkers |
WO2024129672A1 (en) | 2022-12-12 | 2024-06-20 | The Broad Institute, Inc. | Trafficked rnas for assessment of cell-cell connectivity and neuroanatomy |
WO2024129969A1 (en) | 2022-12-14 | 2024-06-20 | Illumina, Inc. | Systems and methods for capture and enrichment of clustered beads on flow cell substrates |
WO2024130031A1 (en) | 2022-12-16 | 2024-06-20 | Illumina, Inc. | Boranes on solid supports |
WO2024137886A1 (en) | 2022-12-21 | 2024-06-27 | Illumina, Inc. | Context-dependent base calling |
WO2024137765A1 (en) | 2022-12-22 | 2024-06-27 | Illumina, Inc. | Transition-metal catalyst compositions and methods for sequencing by synthesis |
WO2024137774A1 (en) | 2022-12-22 | 2024-06-27 | Illumina, Inc. | Palladium catalyst compositions and methods for sequencing by synthesis |
WO2024145154A1 (en) | 2022-12-27 | 2024-07-04 | Illumina, Inc. | Methods of sequencing using 3´ allyl blocked nucleotides |
WO2024147904A1 (en) | 2023-01-06 | 2024-07-11 | Illumina, Inc. | Reducing uracils by polymerase |
WO2024167954A1 (en) | 2023-02-06 | 2024-08-15 | Illumina, Inc. | Determining and removing inter-cluster light interference |
WO2024173756A1 (en) | 2023-02-17 | 2024-08-22 | Illumina, Inc. | Cell-free dna signals as biomarkers of preeclampsia |
CN117886850A (en) * | 2024-03-14 | 2024-04-16 | 深圳赛陆医疗科技有限公司 | Preparation method of azide compound |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200399692A1 (en) | Modified nucleotides | |
DK3147292T3 (en) | LABELED NUCLEOTIDES | |
US20170002408A1 (en) | Labelled nucleotides | |
US20100028885A1 (en) | Labelled nucleotides | |
US11028115B2 (en) | Labelled nucleotides | |
ES2786983T3 (en) | Modified nucleotides for polynucleotide sequencing |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
ENP | Entry into the national phase |
Ref document number: 0405884 Country of ref document: GB Kind code of ref document: A Free format text: PCT FILING DATE = 20030822 |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2003792519 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2005501219 Country of ref document: JP |
|
WWP | Wipo information: published in national office |
Ref document number: 2003792519 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2007166705 Country of ref document: US Ref document number: 10525401 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 10525401 Country of ref document: US |