WO2001020024A2 - Verfahren zum ermitteln von nuklein- und/oder aminosäuresequenzen - Google Patents
Verfahren zum ermitteln von nuklein- und/oder aminosäuresequenzen Download PDFInfo
- Publication number
- WO2001020024A2 WO2001020024A2 PCT/EP2000/007953 EP0007953W WO0120024A2 WO 2001020024 A2 WO2001020024 A2 WO 2001020024A2 EP 0007953 W EP0007953 W EP 0007953W WO 0120024 A2 WO0120024 A2 WO 0120024A2
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- WIPO (PCT)
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- sequences
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Classifications
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- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
- G16B30/10—Sequence alignment; Homology search
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
Definitions
- the present invention relates to a method for the detection of DNA and / or nucleic acid sequences and in particular to a method for the detection of such DNA and / or nucleic acid sequences of a given species (hereinafter referred to as "type sequences") which have a potentially increased significance and which are therefore particularly worthwhile research objects.
- the present invention is based on the object of creating a method for determining DNA and / or nucleic acid sequences, in which those DNA and / or nucleic acid sequences that have a potentially increased significance are specifically selected, that is to say which can be examined with significantly less research effort in terms of specific functions, in particular with regard to a potential relevance to the disease, than would be possible with the other DNA sequences that were not selected in this way.
- steps b and c could be carried out first and then step a of claim 1.
- any type sequences of a species of interest are determined using biological or genetic engineering methods.
- the determined type sequences are in a usual nomenclature as a letter code, the z. B. consists of four letters, stored in a first database.
- step b all known DNA and / or nucleic acid sequences of a given group of biological species or classes are recorded in a second database in which in general, the functional meanings of such sequences are stored together with the sequences.
- publicly accessible databases also sometimes contain additional information about the individual sequences.
- bio-sequences sequences originating from several species
- sequences of the species of interest are referred to throughout here as “species sequences”.
- the given group of species or classes may, but need not, contain the species of interest.
- step c the bio sequences recorded in a database according to step b are compared in a homology test with the already known and possibly stored in the same database type sequences (of the type of interest), with the simplest possible homology test due to the relatively large number of sequences to be compared should be used. If the homology between the known art sequences and the known bio sequences then lies above a certain threshold value, then all of these bio sequences homologous to known art sequences are separated out from the database to be considered further in accordance with step d. This means that the amount of the remaining known bio sequences compared to the publicly known bio sequences is not only reduced by a restriction to a group of specific species, but also to those sequences for which no homologous species sequences have been determined to date.
- step e The DNA / nucleic acid sequences stored or newly determined according to step a are then compared in step e with this remaining, reduced stock of bio sequences in a homology test.
- the type sequence and the biological sequence homologous to it are expediently adapted to one another in order to confirm the homology and to better understand the corresponding sections of the sequences. If the homology is above a predetermined second limit value, the relevant bio sequences are stored in accordance with step f together with at least one link that uniquely identifies the associated bio sequence, or are output as a potentially significant type sequence.
- references are recorded in the publicly accessible databases, which are stored there in the second, public database relating to biological sequences, namely to the bio-sequences, which were previously determined as homologs to new art sequences, preferably using and evaluating such information that points to a taxonomically organized database.
- a taxonomically organized database contains selected keywords for the respective biological sequences according to uniform scientific criteria, which are then compared in step h with a predetermined list of keywords, which list is in turn selected so that it covers the research areas of a user.
- the relevant bio sequence and the associated type sequence are therefore only obtained in the data stock to be defined as worthwhile target objects if there are correspondences between a given keyword list and the keywords assigned according to taxonomic criteria in the corresponding database (third database).
- the relevant keywords which in a way represent functional meanings, in turn allow more targeted research into the special properties of a style sequence.
- the database in which newly determined style sequences are stored for further investigation can be a public database, but is usually a private database to which only the user or a few users have access, but not the public.
- the second database which also contains additional information on the relevant bio-sequences and references to other databases and information stored therein, generally has public access.
- a third database which is particularly suitable for the purposes of the present invention and contains keywords (MeSH terms) selected according to taxonomic criteria is the so-called “MEDLINE” database.
- This database contains an identification number for each biomedical reference and additional information together with a A number of other data, including keywords that are referred to as "medicai subject headings".
- keywords that are referred to as "medicai subject headings”.
- the MEDLINE database contains a so-called sequence identifier, which is preferably used as one of the necessary links.
- the method according to the invention automatically passing homology tests and targeted filtering and Apart from information sources, comprehensive information about an art sequence is generated, which characterize the meaning and function of the sequence and enable targeted research. All type sequences for which functions and meanings can be determined in this way are supplemented by this additional information. However, they can be accessed again at any time if the database in the second (publicly accessible) database has been expanded accordingly, so that in this way, separate art sequences can later turn out to be worthwhile target objects.
- the homology tests that are carried out between type sequences and bio sequences are preferably carried out in a pipeline process, so that complete data sets do not always have to be recorded and managed.
- FIG. 2 shows a diagram of databases and database links as they are used for the further evaluation of information according to the present invention
- FIG. 3 shows the display of a screen display with control fields and information fields for a (hypothetical) nucleic acid sequence.
- the public sequence database already contains data about the species of interest. Therefore, a homology test is first carried out between the sequences of the species of interest documented in the public database with the bio-sequences of the selected group of species stored in the same database. All bio sequences that are homologous to the art sequences already stored in the public database are discarded, since they have apparently already been or are the subject of corresponding research.
- results of this method step are expediently logged, so that when the same process is repeated, e.g. B. a week later, all bio sequences that have already been sorted out are disregarded from the outset, which speeds up the process considerably.
- the homology test can then be limited to the newly added biological sequences or, conversely, the previously not separated biological sequences must still be compared in a homology test with newly added biological sequences.
- bio sequences are then compared with the newly determined art sequences in a homology test.
- homologous bio-sequences are found for some of the newly determined art sequences.
- a list or table of the type sequences and the newly found, homologous bio-sequences is then prepared, and additional information from the public database is also adopted in this table or list.
- a further step (h) of the method consists in classifying the type sequences output or stored in step f), ie. H. Classification (sorting) into certain classes of sequences by linguistic analysis of text definitions of the additional information stored for the homologous bio-sequences. This enables a division into partial data records, which in turn can only be supplemented by a part of the other databases
- step i the property information of the homologous biological sequences to be assigned to the potentially significant type sequences is supplemented by recording information (links) on the biological sequences recorded according to step f) in the second database on at least a third database and recording the biological sequences mentioned in the third database stored information
- the third database should provide a classification that is taxonomically organized in at least some areas, preferably the so-called MEDLINE database.
- the keywords assigned to the respective bio sequences according to taxonomic criteria are compared with a predetermined list or file of keywords, and matching keywords as well as the relevant bio sequences and the homologous art sequences sequences or an identifier of the same, for which matching keywords with the specified list of keywords were found, are output.
- B. can be selected from the group consisting of the Unigene, Genemap and GDB (new) as well as OMIM, KEGG and UMLS databases.
- the species of interest is primarily that of Homo sapiens, but the method according to the invention can also be used for another species with a substantially similar purpose.
- step c in claim 1 already known species sequences of the species of interest are compared with the biological sequences in a homology test which belong to a predetermined group of biological sequences which are stored in the second database.
- a further homology test is then carried out with the type sequences which were determined in accordance with step a, using the bio sequences remaining from the second database, which had not previously been determined as a homologue to known type sequences.
- This step is designated in Fig. 1 with "Blastn proprietary genes”. If homologous bio-sequences have been found, the best possible adaptation and alignment takes place (this step is labeled "bestfit" in FIG. 1) and the data characterizing the adaptation, length and alignment are stored together with the relevant sequence.
- the status 0 assigned to the corresponding bio sequences means that these bio sequences continue to remain in the pool of data of interest.
- bio-sequences remain in the reduced and interesting data pool for which homologues could neither be found under the determined art sequences nor under the already known art sequences.
- a screen display is shown schematically, which a mortgage results of a determination of potentially significant style sequences according to the invention. It should be pointed out, however, that the result shown is not a real product, but merely a hypothetical, artificially synthesized result, which, however, can in principle be used to read off all the essential steps and results of a typical exemplary embodiment.
- the left side of the screen shows a number of command and parameter fields that the user can operate. For example, he selects a limit value parameter in field 1.2, which specifies the minimum length of homology between type sequence and bio sequence, which according to the homology test and the best possible adaptation match the nucleic acids of the homologous sequence. The limit of a percentage match is shown in field 1.3. In field 1.4 e.g. a keyword is entered which is to be searched in connection with the corresponding homologous sequences.
- the other control panels are self-explanatory.
- Fig. 3 shows that 124 species sequences have one or more bio-sequences which are homologous with a percentage identity greater than 95% and have a homology length greater than 500 base pairs.
- the MeSH entries have terms that are mainly associated with CNS (Central Nervous System).
- Fig. 3 shows the fifth style sequence out of the 124 entries, which is designated with the number sequence 44567.
- the biosequences, which are homologous with the species sequence are indicated in the right half of the picture under "seeds".
- the Medline database and the MEDLINE identifier (block "Medline ID"), which is registered in many other databases, plays a key role here.
- the sequences given under "seeds" are characterized by a gene bank identifier.
- This Entries identified by the genebank identifier can also contain medline identifiers, among other things.
- the titles of the corresponding entries can be determined from the MEDLINE database using this Medline identifier.
- references to certain enzymes which are associated with the gene segment in question are often stored in this database, and this in turn results in the biochemical reaction pathways which are influenced by these enzymes.
- the MEDLINE identifier can also be used to obtain further information from other databases, e.g. about pathological information, the location of genes on certain chromosome sections, etc.
- the sequence 44567 shows the biochemical name, the creation date of the information, and the position of the gene segment on a chromosome at 17q23. Beneath this are genes that are located on the same chromosome arm.
- the UNIGENE database contains information about clusters from gene fragments (EST clusters) that are identified by a specific number (Hs.198237).
- the number of ESTs in this cluster in relation to the total number of components of the present sequence is given as 54/82.
- Proangiotensin-angiotensin indicates the most likely metabolic pathways or chemical reactions to which the known bio-sequences belong.
- BRAIN also indicates the organ in which the relevant sequences are found most frequently. The organ distribution of the EST components is illustrated by different bar lengths. The most likely area of a disease indication, which was determined in connection with the data comparison, is indicated with CNS. In the left half you can still see a horizontal row of bars, with the length of these bars corresponding to the type sequence and the associated bio-sequences or sequence sections indicated in the corresponding line.
- the bio-sequences are listed in detail under "seeds", including their percentage agreement and the length of the corresponding sequence segments.
- the titles of the relevant magazines, the enzymes, and various keywords are also given.
- KIF Knowledge Interchange Format
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Bioinformatics & Computational Biology (AREA)
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Abstract
Description
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU72759/00A AU7275900A (en) | 1999-09-01 | 2000-08-16 | Method for determining nucleic and/or amino acid sequences |
JP2001523795A JP2003509062A (ja) | 1999-09-01 | 2000-08-16 | 核酸および/またはアミノ酸配列の決定方法 |
EP00960458A EP1224325A2 (de) | 1999-09-01 | 2000-08-16 | Verfahren zum ermitteln von nuklein- und/oder aminosäuresequenzen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19941606.0 | 1999-09-01 | ||
DE19941606A DE19941606A1 (de) | 1999-09-01 | 1999-09-01 | Verfahren zum Ermitteln von Nuklein- und/oder Aminosäuresequenzen |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2001020024A2 true WO2001020024A2 (de) | 2001-03-22 |
WO2001020024A3 WO2001020024A3 (de) | 2002-05-23 |
Family
ID=7920397
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2000/007953 WO2001020024A2 (de) | 1999-09-01 | 2000-08-16 | Verfahren zum ermitteln von nuklein- und/oder aminosäuresequenzen |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1224325A2 (de) |
JP (1) | JP2003509062A (de) |
AU (1) | AU7275900A (de) |
DE (1) | DE19941606A1 (de) |
WO (1) | WO2001020024A2 (de) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1373885A2 (de) * | 2001-03-29 | 2004-01-02 | Evogene Ltd. | Zur identifizierung, isolierung und verwendung von die genexpression in einem organismus regulierenden nukleotidsequenzen geeignete verfahren, plattformen und kits |
US7695968B2 (en) | 2003-03-12 | 2010-04-13 | Evogene Ltd. | Nucleotide sequences regulating gene expression and constructs and methods utilizing same |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002269114A (ja) * | 2001-03-14 | 2002-09-20 | Kousaku Ookubo | 知識データベース及び知識データベースの構築方法 |
DE10323917A1 (de) * | 2003-05-23 | 2004-12-16 | Protagen Ag | Verfahren und System zur Aufklärung der Primärstruktur von Biopolymeren |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5871697A (en) * | 1995-10-24 | 1999-02-16 | Curagen Corporation | Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing |
WO2000063687A1 (en) * | 1999-04-15 | 2000-10-26 | The Trustees Of Columbia University In The City Of New York | Gene discovery through comparisons of networks of structural and functional relationships among known genes and proteins |
WO2001013105A1 (en) * | 1999-07-30 | 2001-02-22 | Agy Therapeutics, Inc. | Techniques for facilitating identification of candidate genes |
-
1999
- 1999-09-01 DE DE19941606A patent/DE19941606A1/de not_active Withdrawn
-
2000
- 2000-08-16 EP EP00960458A patent/EP1224325A2/de not_active Withdrawn
- 2000-08-16 JP JP2001523795A patent/JP2003509062A/ja active Pending
- 2000-08-16 AU AU72759/00A patent/AU7275900A/en not_active Abandoned
- 2000-08-16 WO PCT/EP2000/007953 patent/WO2001020024A2/de not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5871697A (en) * | 1995-10-24 | 1999-02-16 | Curagen Corporation | Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing |
WO2000063687A1 (en) * | 1999-04-15 | 2000-10-26 | The Trustees Of Columbia University In The City Of New York | Gene discovery through comparisons of networks of structural and functional relationships among known genes and proteins |
WO2001013105A1 (en) * | 1999-07-30 | 2001-02-22 | Agy Therapeutics, Inc. | Techniques for facilitating identification of candidate genes |
Non-Patent Citations (2)
Title |
---|
MADDEN T L ET AL: "APPLICATIONS OF NETWORK BLAST SERVER" METHODS IN ENZYMOLOGY,ACADEMIC PRESS INC, SAN DIEGO, CA,US, Bd. 266, 1996, Seiten 131-141, XP001006313 ISSN: 0076-6879 * |
WORLEY K C ET AL: "BEAUTY: AN ENHANCED BLAST-BASED SEARCH TOOL THAT INTEGRATES MULTIPLE BIOLOGICAL INFORMATION RESOURCES INTO SEQUENCE SIMILARITY SEARCH RESULTS" GENOME RESEARCH,US,COLD SPRING HARBOR LABORATORY PRESS, Bd. 5, Nr. 2, 1. September 1995 (1995-09-01), Seiten 173-184, XP000534406 ISSN: 1088-9051 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1373885A2 (de) * | 2001-03-29 | 2004-01-02 | Evogene Ltd. | Zur identifizierung, isolierung und verwendung von die genexpression in einem organismus regulierenden nukleotidsequenzen geeignete verfahren, plattformen und kits |
EP1373885A4 (de) * | 2001-03-29 | 2004-06-23 | Evogene Ltd | Zur identifizierung, isolierung und verwendung von die genexpression in einem organismus regulierenden nukleotidsequenzen geeignete verfahren, plattformen und kits |
US7695968B2 (en) | 2003-03-12 | 2010-04-13 | Evogene Ltd. | Nucleotide sequences regulating gene expression and constructs and methods utilizing same |
Also Published As
Publication number | Publication date |
---|---|
EP1224325A2 (de) | 2002-07-24 |
AU7275900A (en) | 2001-04-17 |
DE19941606A1 (de) | 2001-03-08 |
JP2003509062A (ja) | 2003-03-11 |
WO2001020024A3 (de) | 2002-05-23 |
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