CN100350406C - Method, system and computer software for providing genomic web portal - Google Patents

Method, system and computer software for providing genomic web portal Download PDF

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CN100350406C
CN100350406C CNB018041396A CN01804139A CN100350406C CN 100350406 C CN100350406 C CN 100350406C CN B018041396 A CNB018041396 A CN B018041396A CN 01804139 A CN01804139 A CN 01804139A CN 100350406 C CN100350406 C CN 100350406C
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probe
group
identifier
user
data
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CN1426534A (en
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大卫M·克拉福德
弗农A·诺维尔
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Affymetrix Inc
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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
    • G16B50/00—ICT programming tools or database systems specially adapted for bioinformatics
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    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
    • G16B25/30—Microarray design
    • 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
    • G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression

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Abstract

Systems, methods, and computer program products are described that process inquiries or orders regarding purchase of biological devices, substances, or related reagents. In some implementations, a user selects probe-set identifiers that identify microarray probe sets capable of enabling detection of biological molecules. Corresponding genes or EST's are identified and are correlated with related product data, which is provided to the user. Further, the user may select products for purchase based on the product data. If so, the user's account may be adjusted based on the purchase order. In the same or other implementations, a local genomic database is periodically updated. In response to a user selection of probe-set identifiers, data related to corresponding genes or EST's is provided to the user from the local genomic database.

Description

Be used to provide the method and system of genomic web portal
Related application
It is No.60/178 that the application requires the U.S. Provisional Patent Application sequence number, 077, title for " be used to provide the method for genomic web portal; system; and computer software " right of priority, this application was filed an application on January 25th, 2000, this in conjunction with reference to its full content to be used for all purposes.
Background technology
The present invention relates to field of bioinformatics, particularly on network, be used to provide the computer system of gene information, method, and product such as the Internet.
For molecular biology, biological chemistry needs a large amount of organizational structures with the research of many relevant health fields and the analysis of the complex data that produced by new experimental technique.Be engaged in these tasks by the field of bioinformatics of fast development.For example referring to, by " the bioinformatics basis " of H.Rashidi and K. Buehler work: biology and medical application ( Application in Biological Science and Medicine) (CRC Press, London, 2000); Bioinformatics: the practical guide of analyzing gene and protein ( A Practical Guide to the Analysis of Gene and Proteine) (B.F.Ouelette and A.D.Bzevanis, eds., Wiley﹠amp; Sons, Inc., 1998), at this in conjunction with full content with reference to them.That summarizes says, a category of bioinformatics is that computing technique is applied to large-scale gene database, usually on the network such as the Internet, distribute and by access to netwoks, so that reach explanation gene structure and/or position, protein function, and the relation between the metabolism processing.
Summary of the invention
It is an expulsive force that promotes the biological information development that microarray technology is used in expansion.Specifically, microarray grows up fast with relevant instrument and computer system, and the data of the expression formula of related gene or expressed sequence tag (EST) in the sampling of large-scale collection organization.In the middle of these things, can use of the sudden change of these data to be used to studying hereditary capacity and to detect related gene and other diseases or condition.More particularly, the data that obtain by the microarray experiment are valuable for research, because in the middle of many other reasons, the numerous disease state comes down to different performance level by range gene and shows its feature, also (for example transcribe (transcripts) by the change in duplicating of hereditary DNA is several or by specific gene, pass through start-up control, provide RNA precursor, or RNA handles) change in the level.Like this, for example, the researcher uses microarray to answer a question: which gene what show in the cell of a pernicious lump is, but not performance or in tissue, do not show in health tissues according to the treatment of a special status? is that show in the special organization structure which gene or EST and do not show in the tissue at other? is that show in special kind which gene or EST and do not show in the kind at other? yet, in the problem of answering these and other, data aggregation is a beginning step.Extracting the information of biological meaning and the testing equipment of design improvement from the lot of data that is produced by microarray technology, is a major challenge to the researchist.What need now is to offer the researcher so that carry out these tasks with advanced instrument and information.
At these needs system, method and computer program product have been described at these and other.In some implementations, a web portal is handled relevant biological plant or the material bought, the perhaps inquiry or the order of relevant reagent.The user selects " probe is provided with identifier " (broad terms that is described below), it can with the probe groups of one or more probes be provided with the group relevant.These probes can the detection of biological molecule.These biomolecule include, but are not limited to this, comprise that the nucleic acid of DNA performance or the mRNA of corresponding gene transcribe and/or show (for convenience, after this this nucleic acid simply be called " mRNA transcribes ").Corresponding gene or EST is identified and relevant with the relevant data that offers the user.With some aspect, the user can select to buy the product based on data.If a purchase is made in user's decision, adjust user's account according to the order of buying.
An advantage of these implementations is based on the result from an initial experiment, can show a user with the product suggestion at experiment.The option table that probe by the user is provided with identifier illustrates these preliminary results, for example by specifying those probes that identifier is set, they are corresponding to the probe that is expressed as quite high-grade differential expression in the sampling of control neutralization test.
In identical or other implementation, a local genome database is by the renewal in cycle.In some aspects, can make this renewal from remote data base.The user that identifier is set in response to probe selects, and the data of related gene or EST are provided to the user from local genome database.On the other hand, the data of related gene or EST are provided to the user to respond user's selection of a gene and/or EST identifier from local gene database.
Some advantages of these implementations comprise the ability that can start a data request based on the result of experiment user.As just an example, user by selecting is provided with identifier corresponding to the probe of high relatively differential gene expression formula and shows these results.In addition, these realizations can also have advantage, because this gene data is local available and do not need to comprise the request that remote data base of inquiry responds the user usually on the time of user request.On the contrary, the inquiry of carrying out the remote data storehouse in cycle, for example a week.Like this, identifier is set, indicates expression formula or the differential expression of a large amount of genes and EST, can be provided to the user to a response apace from local gene database even user's selection comprises a large amount of probes.Because the multipath of remote data base or batch inquiry and avoided effective delay usually.
In addition, in aforesaid and other realization, described a kind of method, placed a computer implemented inquiry or order relevant one or more products of buying by a user.The user selects first group of probe that identifier is set, this selection is sent to an entrance system through the Internet, this system can have the probe of selecting corresponding to the user one or more genes of identifier or the related data of EST are set.The user receives relevant data from entrance system.The user can select the data of some or all otherwise express other expectation and buy the product relevant with data.If the user selects to buy a product, therefore user's account is adjusted.
In some implementations, a kind of system has been described, be used to provide the data of relevant one or more genes or EST, wherein each gene or EST have one at least corresponding to the probe setting that identifier identification is set by a probe, and can detect a biological molecule.Biological molecule can be that a kind of nucleic acid or a kind of mRNA of a corresponding gene transcribes.As mentioned above, one or more probes are provided with identifier can comprise a gene or EST identifier, inserts numbering such as one.System comprises an input manager, and it receives user's selection that first group of probe is provided with identifier; A gene determiner, gene or EST that identification is provided with corresponding to the probe that the identifier sign is set by first group of probe; A correlator is with data related gene or EST; With an output manager, provide data to the user.The input and output manager of these instruments can be coupled to the user through the Internet.
It can be the subclass that the probe of second group of probe setting is provided with identifier that first group of probe is provided with identifier, and the probe setting has the expression formula that can detect corresponding gene or EST or the ability of differential expression.For example, a graphical user interface user who provides by a probe array software application can select this subclass.For example can make this selection like this, by drawing a circle round outlier in the scatter-plot that is provided with at the expression probe, wherein this outlier represents to have the probe setting of the differential expression of relative high-order.As the example of many possible other, the highlighted input item user who by probe identifier is set in the form of an instruction can select subclass.
Typically the probe setting being placed on one or more probe arrays, as mentioned, can be any various types of microarray, such as using VLSIPS TMThose of technology (describing below) comprehensive or the point-like array.Therefore, term " probe setting " is generally understood as and not only comprises one group of comprehensive probe, for example according to VLSIPS TMTechnology, but also comprise the one or more points that deposit according to various point-like array techniques (also being described below).These points for example are oligonucleotide or other cDNA vegetative propagation or the PCR product that produce from those clones.These data can comprise about availability, price, composition, the product data of applicability, the order that perhaps comprises the various products of biological plant or material, perhaps a kind of reagent, it can be used for biological plant or material, perhaps Fu Jia information, such as nucleotide or protein order information or location or functional annotation information.As some examples, this equipment can be a probe array or a slide, and perhaps material can be the clone, oligonucleotide, antibody, or protein.
Other implementation is directly at the method that is used to provide about the data of one or more genes or EST, wherein each gene or EST have at least by probe and the corresponding probe setting of identifier identification are set and can carry out the detection of biomolecule.Biomolecule can be that the mRNA of a kind of nucleic acid or a kind of corresponding gene transcribes.The method comprising the steps of: receive user's selection that first group of probe is provided with identifier; Gene or EST that identification is provided with corresponding to the probe that the identifier sign is set by first group of probe; Carry out relevant with data with gene or EST; And data are offered the user.The instrument that also has other is directly at a kind of computer program of realizing preceding method.
Realization in addition is used to place the order instruction of a computer implemented inquiry or the one or more products of relevant purchase directly at a kind of method.The method comprising the steps of: receive user's selection that first group of one or more probe is provided with identifier on subscriber computer, wherein each probe is provided with probe setting that can detect the expression formula of corresponding gene of identifier identification; The user is selected to be provided to an entrance system by the Internet, this entrance system can enough data with carry out relevant corresponding to one or more genes or EST that the probe setting that identifier identifies is set by first group of probe; And from the relevant data of entrance system reception.In addition, the user can also select the product data that are used to buy.
Another is realized directly at a kind of system, be used to provide the data of relevant one or more genes or EST, wherein each gene or EST have one at least and the corresponding probe setting of identifier sign are set and can be detected a biomolecule by probe.Biomolecule can be that an a kind of nucleic acid or an a kind of mRNA corresponding to gene transcribe.System comprises a data librarian, and it is updated periodically a local gene database that includes correlation gene or EST data; An input manager, the probe that receives user's selection is provided with identifier; A subscriber service management device is provided with the local gene data database data that identifier is configured with correlation gene or EST corresponding to probe; And an output manager, data are provided to the user.
In above-mentioned realization, database manager can periodically update local gene database, week for example, use sequence data, external structure or locator data, the splicing variable data, mark structure or locator data, polymorphic data, data of the same clan, protein grouped data of the same clan, path data, interchangeable unnamed gene data, the document enumerated data, explain data, other genome or protein group data, perhaps any their combination.By may being to finish this renewal periodically communicating by letter on the Internet with remote data base.Can comprise any hundreds of public or proprietary remote data base, such as GenBank, GenBank New, SwissPort, GenPept, DB EST, Unigene, PIR, Prosite, PFAM, Prodom, Blocks, PDB, PDBfinder, EC Enzyme, Kegg Pathway, Kegg Ligand, OMIM, OMIM Map, OMIM ALLele, DB SNP, and/or PubMed.And database manager is periodically communicated by letter with remote data base, typically (but not necessarily) do not respond a user's request, and the probe that input manager typical (but not necessarily) receives the user dynamically is provided with the selection of identifier.The word of Shi Yonging " dynamically " is intended to represent a user's of real-time response inquiry in this article.
In another is realized, a kind of system that is used to provide product data has been described, these data can comprise the biologics data.System has an input manager, and it receives a gene from the user, EST, and/or probe is provided with identifier.For example, the user can stipulate one or more gene access codes.In addition, system has a subscriber service management device, the relevant or associated gene with one or more product data, and EST, and/or probe is provided with identifier.The subscriber service management device can be selected collaborative data librarian in addition, from one or more parts and/or remote data base or other part or remote data source obtain product data, for example from a webpage.Also comprise an output manager in this external system, provide product data to arrive the user.In some respects, user account can be adjusted,, a supplier's account can be adjusted perhaps for the user who depends on the seller according to buying.Receive information and information is provided to the user and can carry out from the user, such as the Internet at a network.In yet another aspect, a kind of method that is used to provide product data has been described, for example, the biologics data.The method comprising the steps of: receive a gene from the user, and EST, and/or probe is provided with identifier; With one or more product data and gene, EST, and/or probe that identifier is set is relevant; From a part and/or a remote data base or other part and/or remote data source obtain product data; With provide product data to arrive the user.This method optionally comprises according to buying adjusts a user account, perhaps adjusts a seller's account for the user who depends on the seller.
Another aspect is a kind of system that is used to provide relevant one or more genes or EST product data.Each gene or EST have at least by a probe and the corresponding probe setting of identifier sign are set and can detect a biomolecule.This system comprises an input manager, receives one or more probes identifier is set; A correlator, that identifier is set is relevant with probe with first group of one or more product data; With an output manager, provide first group of data to the user.Another aspect is a kind of system that is used to provide about the product data of one or more genes or EST.This system comprises an input manager, receives one or more genes and/or EST identifier; A correlator is relevant with identifier with first group of one or more product data; With an output manager, provide first group of data to the user.
An additional aspect is a kind of method that is used to provide relevant one or more genes or EST product data.Each gene or EST have at least by a probe and the corresponding probe setting of identifier sign are set and can detect a biomolecule.The method comprising the steps of, receives one or more probes identifier is set; That identifier is set is relevant with probe with first group of one or more product data; With provide first group of data to the user.Another aspect provides a kind of method of relevant one or more genes or EST product data.The method comprising the steps of, receives one or more genes and/or EST identifier; First group with one or more product data is carried out relevant with identifier; With provide first group of data to the user.
According to another aspect of the present invention, a kind of system that is used to provide relevant one or more genes or EST product data has been described.This system comprises receiving trap, is used for receiving one or more genes or EST identifier on the Internet; Relevant apparatus is used for carrying out relevant with one or more product data with gene or EST identifier; And generator, be used to provide product data to the user.
According to another aspect of the present invention, a kind of system that is used to provide relevant one or more genes or EST product data has been described, wherein each gene or EST have the corresponding probe setting that the identifier sign is set by probe at least, and can detect a biomolecule.This system comprises: receiving trap is used for receiving first group the selection that one or more probes are provided with identifier from the user; Relevant apparatus is used for first group of probe with first group with one or more product data and identifier is set carries out relevant; And generator, be used to provide first group of data to the user.
One additional aspect, a kind of system that is used to provide relevant one or more genes or EST data has been described, wherein each gene or EST have corresponding probe setting being provided with by probe that identifier represents and can the detection of biological molecule at least.This system comprises updating device, is used to be updated periodically a local gene database that includes correlation gene or EST data; The input manager device is used for receiving first group the selection that one or more probes are provided with identifier from the user; Data administrator is used for being updated periodically relevant first group of data that the gene or the EST of identifier are set corresponding to first group of probe from local gene database; And generator, be used to provide first group of data to the user.
Above-mentioned implementation needn't comprise each other or repel and can make up by any way, be non-conflict and have various possiblely, no matter they are with identical, or different aspects or implementation occur.The description of a realization is not to be used for other implementations are limited.In addition, other local any one that describe or each functions in this instructions, step, operation, or technology can be combined in any one or a plurality of function of describing in the general introduction, step with interchangeable implementation, operation, or technology.Therefore, above-mentioned implementation only is example rather than is used for limiting.
Description of drawings
The following detailed description of carrying out in conjunction with the drawings, above-mentioned advantage with other will become more apparent.In the accompanying drawings, identical reference number is represented identical structure or method step, and the numbering of leftmost this figure of one or two numeral explanation of reference number, this reference unit is to occur (for example, unit 180 occurs in Fig. 1 for the first time and unit 1020 occurs in Figure 10 for the first time) for the first time in the drawings.In FBD (function block diagram), rectangle ordinary representation functional unit, parallelogram ordinary representation data, the data of the rectangle ordinary representation storage on band arc limit, have a pair of predefined functional unit of double-edged rectangle ordinary representation and trapezoidal ordinary representation manual operation.In method flow diagram, rectangle ordinary representation method step and rhombus ordinary representation identifying unit.Yet all these usages just are intended to typical case or example, rather than are used for restricted.
Fig. 1 is the functional-block diagram that comprises a probe array analytic system of a scanner and a computer system, can the object computer application program on computer system, be used to provide probe that identifier is set and be used to receive pin be used to handle the user that probe is provided with identifier and select;
Fig. 2 is the functional-block diagram of an embodiment of probe array analysis application, the as directed application program of storing at the system storage of the computer system of Fig. 1 of being used for;
Fig. 3 is the functional-block diagram that is used for obtaining through the Internet conventional system of gene information;
Fig. 4 is the functional-block diagram of an embodiment that is coupled to remote data base and webpage through the Internet and is coupled to gene inlet of client, comprises the network of the user machine system with Fig. 1;
Fig. 5 is the functional-block diagram of an embodiment of the gene inlet of Fig. 4, comprises a database server, the example embodiment of inlet appliance computer system and inlet end Internet server;
Fig. 6 is a reduced graph, and an embodiment of expression computer utility platform is used for realizing that in conjunction with the client shown in Fig. 4 the gene of Figure 4 and 5 enters the mouth;
Fig. 7 is the method flow diagram of an embodiment, is used to offer a subscriber-related gene expression formula, perhaps differential expression, the gene prod information of experimental result;
Fig. 8 is the functional-block diagram of an embodiment using of subscriber service management device can carrying out in the inlet appliance computer system of Fig. 5;
Fig. 9 is a reduced graph, represents that a gene or probe are provided with the embodiment of identifier to database, such as passing through the method for the subscriber service management device of Fig. 8 in conjunction with Fig. 7;
Figure 10 is the embodiment of a GUI, can produce by the probe array analytical applications of Fig. 2; And
Figure 11 is the embodiment of another GUI, can produce by the probe array analytical applications of Fig. 2.
Embodiment
Now, in conjunction with coming descriptive system, method and computer product with reference to an example embodiment of gene inlet 400.Shown inlet 400 is in the internet environment among Fig. 4, and has carried out more detailed example in Fig. 5-11.
In typical a realization, inlet 400 can be used for from the experiment that has probe array relevant result's information being offered a user.This experiment generally includes uses right hybridization of scanning device detector probe target and the hybridization by various software application analyzing and testing, is described in conjunction with Fig. 1 and 2 now.
Probe array 103
Various technology and science and technology can be used to deposit or synthesize the intensive array of the biomaterial on a substrate or holder.For example, by the Affymetrix  GeneChip  array of California Santa Clara Affymetrix company limited manufacturing, according to being called VLSIPS sometimes TMThe technology of (ultra-large fixed polymer is comprehensive) is synthesized.VLSIPS TMAll there is description some aspects of technology in following United States Patent (USP): 5,143,854 (Pirrung, et al.); 5,445,934 (Fodor, et al.); 5,744,305 (fodor, et al.); 6,022,963 (Mcgall, et al.); With 6,083,697 (Beecher, et al.) exist.At this as a reference in conjunction with the full content of these patents.The probe of these arrays is made up of oligonucleotide, and it synthesizes by certain methods, and this method comprises the step that activates a substrate area and contact substrate then with the monomer solution of selection.The zone that is activated shows with a light source that by a mask this is identical with the camera technique that uses in making integrated circuit.Other zones of substrate keep unactivated state, because mask has been blocked the irradiation to them.By the different zone group of reconditioning with contact different monolithic solution with substrate, on substrate, produced the different array of polymkeric substance.Various other steps in the various realizations of these methods, have been used, such as the unreacted monolithic solution of washing from substrate.
These probes usually use together with the Biosample of label, such as cell, and protein, gene or EST, other dna sequence dna, or other bio-element.This be called these samples of " target " processed in case they with probe array in definite probe space on be associated.For example, the Biosample of one or more chemical tags, promptly target is distributed on probe array.Compensation probe hybridization and remaining on the position of probe on some targets and the space at least, the target of non-hybridization simultaneously is by flush away.These have their " marks " or " label " hybridization target thereby with the compensation probe target relevant.The probe and the target of hybridization can be known as " probe-target to " sometimes.Detect these to can be for various purposes, such as determining whether that the acid of a kind of target nucleoprotein has and a nucleotide sequence that specific reference sequences is identical or different.For example referring to, U.S. Patent No. 5,837,832, relate to and combine top content.Other use comprises that the gene expression formula monitors and assessment (for example referring to, U.S. Patent No. 5,800,992 (Fodor, et al.); U.S. Patent No. 6,040,138 (Lockhart, et al.); With international application no PCT/US98/15151, be disclosed as WO99/05323 (BALABAN, et al.)), gene type (U.S. Patent No. 5,856,092, Dal, et al.), or the detection of other nucleoprotein acid.Above-mentioned ' 992 ', ' 138 ' and ' 092 ' patent, and publication WO99/05323, this for all purposes in conjunction with reference to their full content.
Existingly be useful at a substrate or supporting other technology of deposition probe.For example, commercial " the point-like array " on micro-eyeglass, made.These arrays comprise liquid dot, and they comprise the complex of potential variation and the biomaterial of concentrate.For example, a point in array can comprise a little billet oligonucleotide in a kind of aqueous solution, and perhaps it can comprise highly enriched rectangular synthetic protein.Affymetrix  417 TMThe array device is a kind of equipment, it is according to these technology and method, the biomaterial array of the intensive compression of deposition on a micro-eyeglass, these technology and method apply for that at PCT PCT/US99/00730 (international publication number WO99/36760) is described, this in conjunction with it full content as a reference.In addition, also there is other the technology be used to produce the point-like array.For example, United States Patent (USP) nO.6,040,193 (Winkler, et al.) are at handling the preparation drops to produce the point-like array.' 193 patents and U.S. Patent No. 5,885,837 (Winkler) have also been described on the substrate or high-volume using microchannel or fine groove on the piece at substrate, so that the array of synthesising biological material.These patents have further described by inertia district on the reaction zone and test point the reaction zone of a substrate have been isolated from each other.At this full content in conjunction with reference ' 193 and ' 837 patents.Other technology is based on the jet flow biomaterial to form a point-like array.The spraying technique of other enforcements can be used such as syring or pressure electronic pump to advance biomaterial.There have various other technology to be used on a substrate or in substrate at present to be synthetic, deposition, or location biomaterial.
In order to ensure suitable explanation term " probe " as used herein, should note the conflicting convention that in pertinent literature, occurs.The word that uses in some articles " probe " does not relate to aforesaid at the biomaterial that is synthesized on the substrate or be deposited on a slide glass, but is known as " target " at this.For avoiding confusion, term " probe " is known as such as according to VLSIPS as used herein TMThose probes that technology is synthetic; So that generate the biomaterial of the deposition of point-like array; With synthetic, deposition, or the sample of location is to form according to other arrays present or WeiLai Technology.Like this, for convenience, after this microarray that forms according to any of these technology can be called " probe array " by common and concentrated area.And term " probe " is not limited to be fixed on the probe in the array format.On the contrary, for other parallel testing equipment, the function of description and method also are useful for genomic information and intelligent e-commerce are provided.For example, these functions and method can be applied to probe identifier is set, be identified on the pearl and pearl in, in the optical fiber, or the fixing probe of other materials or media.
Typical probe occurs by detecting that transcribing of mRNA exists or abundance can detect corresponding gene or the expression formula of EST in target.CRNA by tags detected can in turn finish this detection, and the cRNA of this label derives among the cDNA that derives of the mRNA from target.Usually, a probe setting is included in the subsequence in unique transcriptional domain and does not correspond to a complete gene order.Relate to one or more at this normally used word " setting "; For example, probe setting can be made up of and one group of probe is provided with identifier and can identifier be set by one or more probes and forms one or more probes.
Scanner 190
Fig. 1 is the functional-block diagram of a system, is particularly useful for analyzing in other things by the probe array of the target of label hybridization.The probe array 103 of the expression hybridization of Fig. 1 can comprise the probe array of any kind, as mentioned above.Use various business equipment can detect the target of the label in hybridization probe array 103, after this be called " scanner " for convenience.The equipment of an example shown in Figure 1 is scanner 190.By from label, detecting fluorescence or other radiation, perhaps pass through to launch, reflection, or the radiation scanning instrument imageable target of scattering.For convenience, after this these are handled the detection that simply is called " radiation " of concentrating usually and use various detection schemes.The type that depends on radiation and other factors.A typical scheme is to use light and other element exciting light to be provided and optionally to collect radiation.In addition, generally include the use photodiode, charge-coupled device, photomultiplier, or similar equipment is so that the various light detector system of radiation are collected in registration.For example, a kind of scanning system of using fluorescence labels is in U.S. Patent No. 5,143, is described in 854, can carry out combination with reference to foregoing.In United States Patent (USP) 5,578,832; 5,631,734; 5,834,758; 5,981,956 and 6,025,601, and scanner or the scanning system of in PCT application PCT/US99/06097 (publication number WO99/47964), having described other, this for all purposes in conjunction with full content with reference to them.
Scanner 190 provides the data of the intensity (can be other feature also, such as color) of the radiation of representing detection, and the position that detects radiation on substrate.These data generally are stored in the memory devices with a kind of form of data file, such as in the system storage 120 of subscriber computer 100.One type data file such as image data file shown in Figure 2 212, generally comprises intensity and positional information corresponding to the element of the subregion of scanning substrate.Term in article " element " means the intensity from this area radiation, and/or other feature, and each represents a single value.When being shown as image that is used to watch or handles, the pictorial element of element, or pixel, this information of ordinary representation.Therefore, for example, when having from the substrate scanning radiation, a pixel represents a single value of the intensity of substrate subregion element.This pixel also can have the other value of the other feature of expression, such as color.For example, detecting the subregion of element of a scanning of high-level radiation therein (after this can represent by the pixel with high brightness, be called " becoming clear " pixel) and low-inensity radiation can represent by a pixel of low-light level (" dimness " pixel).Interchangeable, can make the value of color of a pixel and represent intensity, color, or other feature of the radiation that detects.Like this, the zone of a high brightness radiation can be shown as red pixel and low-light level radiation areas can be shown as blue pixel.As another example, the radiation of the detection of a wavelength on the specific subregion of substrate can be expressed as red pixel and the radiation of second wavelength that detects on another subregion can be represented by a kind of approaching blue pixel.Many other schemes are known.
Probe array analytical applications 199
General, people can check the image that the data by in an image file printing or that show constitute and can discern those is that become clear or dim unit, perhaps discerns by a pixel characteristic (such as color) in addition.Yet this needs frequent with a kind of robotization, and gageable and repeated mode provides this information, this and various Flame Image Process and/or analytical technology compatibility mutually.For example, the computer utility by relevant position can provide information to be used for handling, the target of on this position, hybridizing with known position probing, and on known position, known identical probe is synthesized or deposits.Then can be derived such as the nucleotide of target dna or RNA or the information of monomer.The technology of making these derivations has been described, for example, in U.S. Patent No. 5,733, among 729 (Lipshutz) and United States Patent (USP) NO.5, in 837,832, at this for various purposes in conjunction with full content with reference to them.
Commercially obtain various computer software application and be used for gated sweep instrument (instrument of handling with other relevant hybridization is such as the hybridization case), and be used to obtain and handle the image file that provides by scanner.Example is the Jaguar from Affymetrix company TMApplication program, this is described in U.S. Provisional Patent Application on the one hand, sequence number is 60/226,999, use in application on August 22nd, 2000 with from the microarray program of Affymetrix, this respect is described in U.S. Provisional Patent Application, sequence number is 60/220,587, applies on July 25th, 2000.The processed images file that is produced by these application programs is further processed usually to extract additional data.Particularly, the data mining software application program is generally used for accessory ID and analyzes the pattern of being concerned about on the biology or the degree of the hybridization that probe is provided with.Affymetrix  Data Mining Tools is the example of such software application.In addition, software application is used to store and manage usually by probe array experiment and the lot of data by above-mentioned Flame Image Process and data mining software generation.Affymetrix  Laboratory Information Management System (LIMS) is an example of these data-management application programs, its these contents are described in U.S. Provisional Patent Application, sequence number is 60/220,645, in submit applications on July 25th, 2000.In addition, various characteristics database by the database management language visit, such as Affymetrix  EASI (expression parsing sequence information) database and database software, offer the relation between setting of researcher's probe and gene or the EST identifier.All patented claims of in this section, mentioning at this in conjunction with full content with reference to them.
Convenience for reference, the computer software application of these types (promptly is used for obtaining and handling image file, data mining, data management, various databases and other the application program of analyzing with relevant probe array) in Fig. 1, concentrate usually be expressed as analysis application 199.Fig. 2 is a functional-block diagram of probe array analysis application 199, and (corresponding to the executable code 199A of application program 199) that is used for carrying out as example storage is in the program of the system storage 120 of the subscriber computer 100 of Fig. 1.
As it will be apparent to those skilled in the art that application program 199 is stored in and/or carrying out from computing machine 100 is not essential; On the contrary, some or all of application program 199 can be stored in and/or carry out from an apps server or other computer platform, and they are connected to computing machine 100 in one network.For example, just has special superiority for relating to the large scale database application program operating, such as Affymetrix  LIMS or Affymetrix  Data Mining Tools (DMT), to carry out from a database server, such as the user database server 412 of Fig. 4.Interchangeable, LIMS, DMT, and/or other application program can be carried out from computing machine 100, but some or all of Yun Hang those application's data storehouses can be stored the public visit on server 412 (may together with a data library manager, such as the Oracle  8.0.5 data base management system (DBMS) from Oracle company) of usefulness thereon.Use commercial available hardware and software just can realize such network arrangement according to known technology, can be used for a LAN or wide area network such as those.Represented subscriber computer 100 to be connected to a LAN (Local Area Network) of user database server 412 (and be connected to user side the Internet client 410, it can be identical computing machine) among Fig. 4 by network cable 480.Same, for gated sweep instrument 190 and the purpose of reception, can make scanner 190 (or a plurality of scanner) be used for a user's network through cable 480 from the data of its input.
With reference to figure 2, executable application program 199A produces various types of data with various forms again, and those are shown as just example.For convenience, term " file " relates to the data that produced by executable application programs 199A or use as used herein, but can use association area known replaceable technology any kind be used for the storage, transmit, and/or the data of operation.In the example of this figure, DAP 210 receives image data files 212 and generation unit intensity file 216 therein from scanner 190.The file 216 of this example comprises each probe by scanner 190 scannings, and expression is for the single value of that probe by the pixel intensity of scanner 190 measurements.Like this, this value is a measurement of abundance that appears at the mRNA of the mark in the target, and this target hybridizes to corresponding probe.Many such mRNA can appear in each probe, can comprise as a probe, and for example, millions of oligonucleotide instrument of design is to detect nRNA.
In the example of example, probe array DAP 210 produces one and comprises relevant test, and the experiment information file 213 of sampling and probe array information, this document are usually by user's 101 inputs.A main function of the DAP 210 of this example is Study document 216 and/or file 212, may be together with information and internal library file (not shown) from file 213, they have stipulated the sequence of probe and control and the details of position.Purpose such as the program of this routine DAP 210 normally provides information, such as the hybridization degree, absolute and/or differential (experimentally two or more) expression formula, genotype relatively, polymorphic and mutation detects, and the result of other analyses.In this embodiment, the analysis output of this DAP 210 of file 215 expressions.DAP 210 can be handled file 215 to generate report file 214, and it can respond user 101 relevant form and requests for content.As those of ordinary skills, be noted that, the file aforesaid and described later that produces by the DAP 210 of example, report, and data representation only is an example, can handle with many other methods, combination is arranged, and/or the data of expression description and other data.
In addition, DAP 210 produce various types of curves, figure, form and other tabular and/or figure such as the expression formula that is included in the analysis data in the file 215.Shown an example in Figure 10, shown a graphical user interface (GUI) 1000, it has distributing drawing window 1010 and sheet format window 1020.In scatter- plot window 1010,1011 pairs in straight line is provided with the grade of organizing the differential expression of measuring by probe in different experiments provide a reference data.The position of point, each some expression is from a probe setting of one or more microarraies, along an axis convention one the experiment or one group the experiment (for example, the experiment of measurement control sampling) degree of the expression formula of middle probe setting, with axle along other, another experiment or organize the intensity grade (for example, measuring the experiment of disease sampling) of the expression formula in the experiment separately.
In Figure 10, user 101 has round one of constellation points 1,016 1014 (the using existing known technology) of circumscribing.In sheet format window 1020, be identified and be described in a row that separates corresponding to each the probe setting of a point in the window 1010.In this embodiment, and as capable input item in the row 1034 is included in the measurement (as at row 1032) of expressing grade in the special test, one indicates whether that there be not (A) in expression formula or have (P) in experiment.Corresponding to the row of point, promptly probe is provided with group, is enclosed in highly being illuminated in window 1020 so that user 101 can be easy to discern the information that the relevant probe of selecting is provided with group in the ring 1014.In addition, as at row 1036, the every row in window 1020 comprises that a probe is provided with identifier.
For example, be provided with by highlight corresponding to this probes of row 1021 and 1022 and go to be illustrated in the window 1010 around its corresponding point.In row 1036 for these row, that is, " input item of M13903_at " and " M14091_at " is respectively that the probe that is used for its corresponding probe setting is provided with identifier.Therefore Figure 10 has illustrated by user 101 to select probe that a lot of technology of identifier are set.Especially, user 101 in current example by the point that centers at window 1010 (and in such cases, the probe of this selection is provided with identifier and comprises the point that centers on) and/or in window 1020, carry out these selections (and in such cases, the probe of this selection is provided with identifier and is included in title in the row 1036) by selecting a row.What as shown in Figure 2, probe was provided with identifier 222 expression these or other can be provided with identifier by applying the probe that is provided for selecting such as DAP 210 by user 101.In addition, when including, the agreement that is used for naming the DAP 210 of probe setting to use of this example represents the access numbering of this gene or the EST information that is provided with corresponding to this probe.For example, be expert at that probe in 1021 is provided with the access numbering of identification name " M13903_at " expression gene or be the EST that is provided with corresponding to this probe of M13903 corresponding to this row.In other example, this corresponding numbering that inserts can directly show.These equipment that insert numbering that are used for being selected by user 101 are to be represented by the access numbering 124 at Fig. 2.Though, as described, the access numbering can play a kind of probe identifier (therefore insert numbering 124 and can be considered to the sub-group that probe is provided with identifier 222) is set, for illustrate and discuss convenient for the purpose of, they are clearly shown that in Fig. 2.
Other executable application 199A also can provide probe that identifier 222 (optionally comprise and insert numbering 224) is set such as Data Mining Tools 220 and give user 101.Another example is database application 230, and one of them illustrative GUI represents in Figure 11.Database application 230 is one and is used for the application program that relevant probe is provided with, usually by probe identifier is set for corresponding gene or EST, such as title, number and/or Symbol recognition.An example of database 230 is the EASI database applications that derive from the Affymetrix company of above-mentioned note.In the example of Figure 11, GUI1100 comprises a query window 1110 and a result window 1120.As shown in figure 11, according to known technology, by selecting the relevant probe setting of a specific probe array 1112 and the comment part 1114 relevant with array 1112 or any and array 1112, user 101 has produced an inquiry effectively.Application program 230 is implemented the search of this database (not shown), and shows the result of this inquiry in window 1120.As below with respect to the explanation of the database of Fig. 5, database application 230 with and relevant database function also can selectively be included in the inlet 400, make the inquiry of satisfying this user by data base administration 512 by inquiry local program library database 516.In both cases, the result of this user inquiring usually comprises the sign of the probe array that satisfies this inquiry, and for example array 1122, and probe is provided with identifier, for example identifier 1124 and 1126.As formerly giving an example, the title " AF058789_at " that is given identifier 1124 can represent it is the access numbering or the EST of the gene that is provided with of the probe corresponding to its sign.User 101 can be provided with identifier with probe of corresponding identifier 1126 highlights, such as shown in Figure 11.The tree structure of generally acknowledging of window 1120 is represented to be arranged on the array 1122 by this probe setting of identifier 1126 identifications.By identifier 1126 identification relevant descriptive information is set also by highlight with this probe, and in identical row, show with the tree structure the same with identifier 1126.
LIM application 225 also is the example as the demonstration of an executable analysis application 199A shown in figure 2.Use 225 and can manage the file that uses or produce by DAP 210 (for example file 212-216), and by the probe array analysis application generation of DMT 220 and other types or file or the data of using.LIM 225 can be along with the storage of past of time, keep, handle and show these and other data that produced by one or more experimenters, goes streamlining management and planning of experiments and proposes report with regard to its result.Based on routine library database (not shown), LIM 225 also can be provided in the SIF information of being represented by file 217 (being described below) among Fig. 2.With respect to application program 230, file 217 can be selected or additionally be stored and maintenance by inlet 400 as mentioned above.For example, SIF information can be stored in the local program library database 516, and by data base administration 512 management, and it can comprise LIM such as LIM 225 or merge some or all its functions.
Subscriber computer 100
Subscriber computer 100 shown in Figure 1 can be the calculation element of special design and equipment, to support and to carry out some or all functions of probe array application program 199.Computing machine 100 also can be any various types of multi-purpose computers of exploitation now or from now on, such as personal computer, the webserver, workstation or other computer platform.Computing machine 100 usually comprises known components and parts, such as processor 105, operating system 110, graphic user interface (GUI) controller 115, system storage 120, memory storage device 125 and input/output control unit 130.Those skilled in the relevant art will understand, there are many possible configurations in the element of computing machine 100, unshowned some components and parts usually can be included in the computing machine 100, such as cache, data backup unit and a lot of other equipment.Processor 105 can be commercial processor, for example the Pentium that is made by Intel company Processor, the SPARC that makes by the Sun micro-system Processor perhaps can be processor a kind of of available other.Processor 105 executive operating systems 110, for example it can be the Windows that derives from Microsoft Type operation system is (such as the Windows NT with SP6a 4.0); Can be from the Unix of many sellers' acquisitions Perhaps Linux type operation system; Other or following operating system; Perhaps their some combination.Operating system 110 and routine package and computer hardware be interface in known manner, and is convenient to the function that the different computer program of writing with various programming languages was coordinated and carried out to processor 105.Operating system 110 is usually collaborative with processor 105, the function of the ingredient of other of coordination and object computer 100.Operating system 110 also provides timetable, input and output control, file and data management, memory management according to known technology fully, and Control on Communication and relevant business.
System storage 120 can be any memory storage equipment known or that occur in the future.For example it comprise any usually available random-access memory (ram), such as the magnetic medium of the hard disk of resident data or tape, such as the optical medium of read and write CD or other memory storage device.Memory storage equipment 125 can be any equipment known or that occur in the future, comprises compact disc driver, tape drive, disk cartridge driver or floppy disk.Such memory storage device 125 generally reads and/or writes from the program storage medium (not shown) respectively, such as compact disc, tape, disk cartridge or flexible plastic disc.These all program storage medium, perhaps other now with or may develop after a while can think computer program.Obviously, usually storage computation machine software program and/or data of these program storage medium.Be also referred to as in this program storage device that computer software programs usually are stored in the system storage 120 and/or combined memory memory device 125 uses of computer control logic.
In certain embodiments, the computer program of describing comprises the medium that the computing machine with steering logic (computer software programs comprise program code) of storage thereon can be used.When being carried out by processor 105, this steering logic makes processor 105 go to be implemented in function described herein.In another embodiment, for example, some function mainly is to implement in the computer hardware that uses the computer hardware state machine.The realization of computer hardware state machine makes that being implemented in function described herein will be conspicuous to persons skilled in the relevant art.
Input/output control unit 130 can comprise and be used to accept and handle known device from any kind of of user profile, no matter is artificial or mechanical, and is no matter local or long-range.Above-mentioned equipment comprises that for example, modem card, network interface unit, sound card or other types are used for the controller of the known input media of any kind of 102.The o controller of input/output control unit 130 can comprise and is used for the controller that presentation information is given the known display device 180 of user's any kind of, no matter is artificial or mechanical, and is no matter local or long-range.If a kind of display device 180 provides visual information, this information usually can be the array that is organized as picture element in logic and/or physically, and picture element often is called as pixel.Graphic user interface (GUI) controller 115 can comprise the known or following software program of any kind of that is used for providing the figure IO interface between computing machine 100 and user 101 and is used for the process user input.In illustrational embodiment, the functional element of this computing machine 100 communicates with one another by system bus 104.Some of these communications can use the telecommunication of network or other types to realize at different embodiment.
For the technician in those relevant fields, if with software implementation, application program 199 can will be obvious via a kind of loading system storer 120 in the input media 102 and/or memory storage device 125.Application program 199 all or part of also can reside in the similar device of ROM (read-only memory) or memory storage device 125, and above-mentioned equipment does not require that application program 199 at first loads via input media 102.Those it will be appreciated by those skilled in the art that, be convenient operation, application program 199 or its part can be loaded in system storage 120 or cache (not shown) or two the above-mentioned storeies in known manner by processor 105.
Obtain the conventional art of genomic data
The some conventional methods that are used for obtaining through the Internet genomic data are available, and some of them are described in by the book that Ouelette and Bzevanis compiled, above being incorporated in as a reference.Fig. 3 is the functional block diagram of the example of an expression simplification.As shown in Figure 3, user 101 can consult any a lot of public or other data with obtain to insert numbering 224 '.As manual operations 312 expressions, (as addressable internet url http in January calendar year 2001: the internet address at national biotechnology information (NCBI) center of // www.ncbi.nlm.nih.gov) National Library starts request 312 to user 101 by enter medical science and National Institutes of Health via any web browser.Especially, user 101 can enter Entrez search and searching system, and it provides information at NCBI from different databases.These databases provide for the sequence of nucleotide sequence, protein, macromolecular structure, whole genome and the information that is relevant to this publish data.Exemplarily supposition, user 101 enters NCBI Entrez nucleotide database 314 in this way, and receives the information that comprises gene or est sequence 316.Especially, if insert numbering 224 ' expression a large amount of (for example 100) interested EST or gene, as the situation of the analysis that can easily do the probe array experiment, the operation task of describing so far expensive time of possibility, perhaps several hours.
User 101 is usually from sequence 316 replication sequence information, and pastes this information by the BLAST webpage 324 (addressable at http://www.ncbi.nlrn.nih.gov/ BLAST/ as January calendar year 2001) of NCBI and enter within the addressable html file.This crowd BLAST by Fig. 3 that the user starts asks 322 operations of representing, if comprise many sequences, it also may be time-consuming and tediously long.BLAST is the abbreviation of basic local fixed-position searching instrument, in this field is well-known, and be made up of the similarity searching program, the sequence library that uses the heuristic algorithm to seek for two protein and DNA goes to seek local location.For example, user 101 can use " blastn " nucleotide sequence database to implement blast search.It may be not all right continuing a lot of hours by the result of this batch blast search of sequence data 326 expression of similar nucleotide and/or protein for user 101.User 101 can manually or use various Software tools to start relatively and estimate 332 then.User 101 can quote report 334 subsequently, with the discovery of explaining search and positioning strategy and for next step experimental requirements
Be input to genome inlet 400 from user 101
Fig. 4 is an exemplary illustration can be connected configuration with genome web portal 400 by user 101 a functional block diagram.Should be able to understand that Fig. 4 just simplifies and illustrative ground, a lot of enforcement and the variation that are connected with the Internet at the network shown in Fig. 4 will be obvious for those those of ordinary skill in the art.
User 101 utilize subscriber computer 100 and aforesaid analysis application 199 (comprise produce and/or access file 212-217 some or all).As shown in Figure 4, in this example, file 212-217 is remained on the user database server 412, subscriber computer 100 is coupled to user database server 412 through network cable 480.Computing machine 100 ', 100 " and in LAN (Local Area Network) or comprise that other user's computer in the wide area network of intranet, the Internet or any other network also can be coupled to server 412 through cable 480.
Should be understood that cable 400 only represents the network connectivty of any kind, but it can comprise cable, transmitter, relay station, the webserver and many not shown are ingredients of obvious other for those persons of ordinary skill in the relevant.Through subscriber computer 100, user 101 Web browser that is provided by user side the Internet client 410 can be provided go to communicate by letter with inlet 400 by the Internet 499.Inlet 400 can be similar to through the Internet 499 with other user and/or user's network service, as by the Internet client 410 ' and 410 " expressions.
As previously mentioned, offer inlet 400 information by user 101 and generally comprise one or more " probe is provided with identifier ".These probes be provided with identifier usually as the result of experiment on probe array, implemented to cause user 101 attention.For example, user 101 can select those probes that can allow to transcribe the sign micro probe array of expression from the detection mRNA of corresponding interested especially gene or EST that identifier is set.As well known in the art, an EST is the fragment that can not characterize gene order fully, yet gene order normally fully and characterize fully.This speech " gene " is generally used for relating to whole sizes of the known array of gene herein, and relates to the gene that can calculate reckoning.In some is implemented, these genes of representative or the concrete sequence of EST by this array detection can be called as " sequence information fragment (SIF) ", and can be recorded in " SIF file " with respect to LIMS 225 operations as mentioned above.In specific enforcement, SIF has thought to represent preferably the part of the consensus sequence that the mRNA from given gene or EST transcribes.This consensus sequence may be obtained by comparison and grouping EST, and also may obtain by comparison EST and genome sequence column information.A SIF is a part that is designed for the consensus sequence of probe on this array particularly.With respect to the operation of web portal 400, suppose that some micro probe array setting can be designed to can detect the expression of gene formula based on est sequence.
As mentioned above, term " probe setting " general reference is come one or more probes of the row's probe on the comfortable microarray.For example, at an Affymetrix GeneChip In the probe array, its middle probe synthetic on substrate, probe setting can be made up of 30 or 40 probes, usually half Be Controlled wherein.These probes common or with them some or all different combinations be considered to represent the expression formula of gene or EST.In the fixed point probe array, one or more points can similarly constitute one " probe setting ".
This term " probe is provided with identifier " is used widely herein, this identifier of wherein a lot of types may with the implication that will be included in this term in.Probe is provided with the symbol of distributing to the purpose that the identification probe is provided with that a type of identifier is title, number or other.This title, number or symbol for example can be the settings of at random being distributed to probe by the manufacturer of this probe array.For example the user can or key in this title and select the probe of this type that identifier is set by highlight.Probe setting as the another kind of type of wanting herein is figured probe setting.For example, those points that can on scatter-plot or other synoptic diagram, show, wherein each point is represented a probe setting.
Typically, on figure the location tables of this point be shown in one or more experiments from mix, mark, target intensity (more detailed description below), signal.Like this, the user perhaps selects one or more points can select a probe that identifier is set by knocking, draw a ring that centers on.Combine in operation with DAP 210, and more particularly, with draw with respect to user 101 that being centered around looses and draw on painting ring 1014, and/or the selection title relevant or insert the example that the numbering combination provides above-mentioned selection with highlight row 1021 or 1022.Other example provides with respect to the row of being selected in database by user 101 1126 in the above, and this database comes relevant probe setting to insert numbering with other genomic information.
As the term that uses herein, the probe of another type is provided with identifier and comprises nucleotide sequence.For example, the specific SIF of illustrative ground supposition is the single order of 500 bases, and it is the part of common sequences or from the sample sequences of EST and/or genome sequence information gathering.Further the one or more probe settings of supposition are designed to represent this SIF.Therefore stipulate that the whole or a part of user of 500 base sequences can think had that corresponding probe is provided with whole or some.As a further example, the user can stipulate the part of 500 base sequences, and it can be that SIF is unique, perhaps also can identify group, consensus sequence and/or the gene grouping of another SIF, EST, EST.Under the sort of situation, this user is provided with identifier for one or more genes or EST regulation probe.In another changed, supposition specific SIF in illustrative ground was the part of specific consensus sequence.Further the part of supposition user regulation consensus sequence is not to be included in this SIF, and is unique to the consensus sequence that will represent or the consensus sequence of gene or EST.Under the sort of situation,, be identifier to be set corresponding to the probe that this SIF identifies this probe setting by user-defined this sequence even user-defined sequence is not included in this SIF.Technician as those relevant fields will be understood that now, and it is possible requiring situation in parallel with respect to the instruction manual of the partial sequence of EST and gene or EST.
Another example that probe is provided with identifier is the access numbering of gene or EST.Gene and EST insert numbering be disclose available.Therefore probe setting can be by the number identification of the gene that inserts numbering or one or more EST and/or be provided with corresponding to this probe.The probe setting and EST's or gene between consistance can in appropriate databases, keep, such as what visited by database application 230 or local program library database 516, wherein this consistance can offer the user.Similarly, concerning using it to disclose available access numbering is provided with identifier as probe the purpose, genetic fragment except that EST or sequence can mapped (for example, by consulting appropriate databases) be given corresponding gene or EST.For example, the user can be interested in product or the genomic information relevant with specific SIF, and specific SIF stems from EST-1 and EST-2.This user can be equipped with in SIF (perhaps the SIF sequence is some or all of) and EST-1 or EST-2 or bipartite consistance.In order to obtain product relevant or genomic data with this SIF, perhaps its partial sequence, this user can select EST-1, EST-2 or both accesses numbering.
Genome web portal 400
Genome web portal 400 offers user 101 and one or more genes or the relevant data of EST.Each gene or EST have the probe setting that probe is provided with identifier identification of passing through of at least one correspondence, as described, property as an illustration and nonrestrictive example, this probe identifier can be number, title, access numbering, symbol, diagrammatic representation (for example or the clauses and subclauses of the tabulation of highlight) or nucleotide sequence.This corresponding probe setting can allow to detect its corresponding expression of gene formula.One or more probes that the response user selects are provided with identifier, and inlet 400 provides genomic information for user 101 and/or about the information of biological products.This information can help user 101 to resolve result of experiment, and designs or implement follow-up experiment.
Fig. 5 is one the functional block diagram of the many possible embodiment of inlet 400.In this example, inlet 400 has the hardware ingredient that comprises three computer platforms: database server 510, Internet server 530 and application server 520.The different functional unit of inlet 400, such as database manager 512, input and output manager 532 and 534, and subscriber service management device 522 is carried out its operation on these computer platforms.Promptly, in typical an enforcement, manager 512,532,534 and 522 function are by the execution of software application and by being carried out by the computer platforms of server 510,530 and 520 representatives.Inlet 400 is at first described with respect to its computer platform, describes with respect to its functional unit then.
Though they typically belong to the computing machine classification that is commonly called server, server 510,520 and 530 each can be any kind known computer platform or future with the exploitation type.But they also can be main frame, workstation or other computer type.They connect by any known or following type of cable or other communication system, and both sides network or do not network.They can be that mutually in fact location or they can separate.Constitute according to type and/or selected computer platform, on any computer platform, can adopt different operating system.Close proper operating system and comprise Windows NT , Sun Solaris, Linux, OS/400, Compaq Tru64, Unix, SGI IRIX, Siemens Reliant Unix or the like.
There is very big advantage in the function of carrying out inlet 400 in this way on a plurality of computer platforms, such as low cost allotment, database conversion or be converted to enterprise application, and/or more effective fire wall.But other configuration also is possible.For example, be well-known for the those skilled in the art of those association areas, except the three stratum server end ingredients of being represented by Fig. 5, so-called dual or N layer structure is possible.For example, referring to the Mastering Enterprise JavaBeans of E. Roman TMAnd Java TM2 platforms (John Wiley ﹠amp; Sons company, NY, 1999) and the Using Enterprise Java of J.Schneider and R.Arora TM(Que company, Indianapolis 1997), for general purpose in its integral body this merge with reference to wherein both.
The very clear many hardware that are used for Internet commerce not shown in Figure 5 can be implemented in the server end structure with relevant software or routine package ingredient.Go protected data and application program, uninterrupted power source supply, LAN switch, webserver route software and many other ingredients all not shown for the ingredient of implementing one or more fire walls.Similarly, various computing machines composition parts and other the type computer that is usually included in the server classification computing platform will be comprised still not shown.For example, these ingredients comprise the ingredient that processor, storage unit, input-output apparatus, bus and described above and subscriber computer 103 are relevant.Those this areas those skilled in the art will easily understand how to realize these and other conventional ingredient.
Inlet 400 functional unit also can be according to various software suppliers and Platform Implementation (though do not get rid of some of inlet 400 or whole functions also can realize with hardware or routine package).Can utilize the product that is used to realize the ecommerce web portal among various commercial products is BEA WebLogic from the BEA system, its " middleware " application program that is so-called.These and other middleware application program is called as " application server " sometimes, but does not obscure with application server 520, and application server 520 is computing machines.The function of these middleware application programs normally will assist other software unit (such as manager 512,522 or 532) to go shared resource and coordination behavior.This target comprises making and writes, keeps and to change this software unit easier, avoiding data jamming, and prevents system in case of system halt or recovers from the system failure.Therefore, these middleware application programs can provide load balance, failure process and fault tolerance degree, and those common technician in relevant field will understand these all features.
Other development is such as the Java from Sun Microsystems, Inc. TM2 platforms can adopt in inlet 400 so that a cover application programming interface (API) to be provided, and especially improve and implement upgradeable and safe ingredient.What derive from the Sun micro-system is called as J2EE (Java TM2 enterprise versions) platform is arranged to the JavaBeans of enterprise and uses.The JavaBeans of enterprise uses the distributed object application program of writing with Java language to simplify the structure of server end ingredient.Therefore, in one embodiment, the functional unit of inlet 400 can be write with Java, and uses J2EE and the JavaBeans of enterprise to realize.As understanding by those this areas those skilled in the art, various other software development methodology or structure can be used for realizing entering the mouth 400 functional unit with and interconnect.
An enforcement of these platforms and ingredient is shown in Figure 6.Fig. 6 is the figure of a simplification, explanation is in user side the Internet client 410 on the user side with in inlet end surf the Internet reciprocation between the input and output manager 532 and 534 of server 530 and the communication among three layers (servers 510,520 and 530) of inlet 400.Browser 605 on client 410 receives HTML documents 620 to server 530 transmissions with from server 530.HTML document 625 comprises applet 627.The browser 605 of operation provides container working time that is used for applet 627 on subscriber computer 103.Manager 532 on server 530 and 534 function can be with Java such as the realization of GUI operation TMPlatform operations realizes by servlet and/or JSP 640.The servlet engine of carrying out on server 530 provides container working time that is used for servlet 640.JSP (java server homepage) from Sun Microsystems, Inc. is a literal class environment that is used for the GUI operation, and a kind of alternatives is the ASP (active server homepage) from Microsoft.App server 650 is the products that are called as middleware in the above, and carries out on application server 520.EJB (the JavaBeans of enterprise TM) be a kind of standard that is given for the beans of enterprise structure, it is an application component.Similarly, CORBA (general object is asked the agent software structure for instructions) is a kind of standard that is used for the distributed object system, that is, be such as Java by CORBA product successively by the CORBA standard TMIDL realizes.The example of the product that a kind of EJB complys with is called as WebLogic in the above.For the technician in those relevant fields, the more detailed data of enforcement that is used for standard, platform, ingredient and other unit of the Internet inlet and itself and client communication is well known.
As mentioned above, a functional unit of inlet 400 is input managers 532.Manager 532 499 receives one group from user 101 through the Internet, and promptly one or more probes are provided with identifier.Manager 532 is handled and is transmitted these information and gives customer service manager 522.These functions are also introduced this server with similar literal reference usually by according to the shared technology implementation of the known operation by Internet server.Another functional unit of inlet 400 is an output manager 534.Also according to those known methods, manager 534 499 provides information by 522 combinations of customer service manager to user 101 through the Internet, and one of them aspect is described as above with respect to Fig. 6.Information by manager 522 combinations is expressed as data 524 in Fig. 5, be labeled as " the response user asks comprehensive genome and/or product web page ".In a sense, these data are provided with on the technical manual of identifier based on the probe that these data are integrated in by user 101 especially at least in part, therefore have shared relation corresponding to this gene of those identifiers and/or EST.Data 524 by manager 534 representatives can realize according to various known methods.As some example, data 524 can comprise HTML or XML document, Email or alternative document or other forms of data.These data can comprise the internet url address, make user 101 to fetch additional HTML, XML or other document or data from remote source.
Inlet 400 further comprises database manager 512.In illustrational embodiment, database manager 512 coordinate from or to storage, the maintenance of the data of any local data base 511,513,514,516 and 518, the transmission that replenishes or the like other.Manager 512 can with the appropriate databases application program, cooperation realizes these functions such as Oracle 8.0.5 data base management system (DBMS).
In some was implemented, manager 512 was updated periodically local genome database 518.Data Update in database 518 comprises with one or more probes corresponding gene or the relevant data of EST is set.This probe setting can use or plan to use on any microarray products, and/or expectation or plan to use in any manufacturer or researchist's microarray products.For example, this probe setting can be included in the GeneChip from the stock of Affymetrix company All probe settings of synthetic on the probe array comprise its Arabidopsis genome array, CYP450 array, drosophila gene group pattern, bacillus coli gene group pattern, GenFlex TMThe genome U74 group of mark array, HIV PRT Plus array, HuGeneFL array, human genome U95 group, HuSNP probe array, Muridae, P53 probe array, mouse gene group U34 group, mouse Neurobiology U34 group, mouse toxicology U34 array or yeast genes group S98 array.This probe setting can comprise that also those are used for user 101 or other synthetic on conventional arrays.But data updated need not so limit in database 518.But it can relate to many genes or EST.The type that can be stored in the data of database 518 is described below with respect to the operation of manager 522, directly regularly gather these data, in database 518, be provided at the local data that keep and give the user from remote source.
The data type of being quoted with respect to database application 230 above database 516 is included in, that is, its corresponding gene or EST with and the relevant data of identifier.Database 516 also comprises SIF and other routine library data.Customer service manager 522 will provide database manager 512 with respect to the information of routine library and other Data Update sometimes.Sometimes, utilize though these information also can be disclosed, load as being used on website, these lastest imformations will be provided by the owner or the supvr of Proprietary Information.
In native product database 514, can similarly provide or obtain such as website from public resource by the seller, sellers or commission merchant by manager 512 canned datas.Relevant product information miscellaneous can be included in the database 514, wherein for example comprises practicality, price, composition, suitability or subscription data.This information can relate to product miscellaneous, comprises the biological plant or the material of all types, the reagent that can be used for biological plant or material of perhaps all types.Several examples only are provided, and can be a kind of oligonucleotide, probe array, clone, antibody or protein as this equipment, material or reagent.The data that are stored in the database 514 also can comprise link, such as the internet url address, to the available far-end address of product data, such as seller's network address.
Database 511 comprises that the probe relevant with the sequence of probe is provided with the information of identifier.Can be used to by manufacturer, the designing probe of probe to fix a point researchist or other people of array or other conventional arrays provides these information.In addition, the application of inlet 400 is not limited to the probe with array format.As described, probe can be fixed on globule, optical fiber or other substrate or the medium or among.Therefore, database 511 may also comprise the information of considering these probe sequences.
Database 519 comprises that user and they are used for and or carries out the account's of commercial affairs information through inlet 400.Can obtain the account information of any kind of from the user, such as the order in current order, past or the like, all will be easily conspicuous for those common art technology people.Simultaneously, according to the known method of in ecommerce, using, can and/or resolve the user and study by record with the reciprocation of inlet 400 with user-dependent information.For example, customer service manager 522 may be noticed the genome area of user interest, their purchase or product inquiry behavior, access frequency of its various business or the like, and this information is offered database manager 512, be used in database 519 storages or renewal.
Another functional unit of inlet 400 is a customer service manager 522.Manager 522 can periodically make database manager 512 go from various information sources, upgrades local genome database 518 such as remote data base 402.For example, according to arbitrarily chronologically successively timetable (for example, every day weekly or the like), according to known method, manager 522 can start search remote data base 402 by working out suitable inquiry, the URL of the various databases 402 of addressing, perhaps the classic method by other is used for by the Internet implementation data search and/or retrieve data or document.These search inquiries and corresponding address can offer output manager 534 in known manner and be used to show to database 402.The answer that input manager 532 receives for inquiry, and provide them to manager 522, provide them to database manager 512 then, be used for more new database 518, all these all according to various known methods be used for management information flow to, from and in internet site.
The administrative aspect of inlet application manager 526 administration portals 400 may utilize the auxiliary of middleware product such as application server product.One of described these administrative tasks can be the regular update that manager 522 deactivation databases 518 are given in the regular instruction of issue.Alternatively, manager 522 can start this task automatically.Need all data in database 518 not be updated according to identical cycle timetable.But, according to different timetables, generally be for different types of data and/or from the Data Update of different information sources.In addition, these timetables can change, and need not be according to the moment of unanimity.That is, can occur later at one day, upgrade once more later at two days then, secondly can continue to change with the different cycles for the renewal of specific data.Several factors can influence through manager 526 or manager 522 determine keep or change these cycles, such as response time from various remote data bases 402, the value of information and/or timeliness in those databases, the cost consideration relevant or the permission of this database with visit, the information content that must visit or the like.
In some is implemented, manager 522 from the data local genome database 518 constitute one group with corresponding to probe group identifier gene or the relevant data of EST are set by user's 101 selections.This user selects and can be transmitted to manager 522 in accordance with known methods by input manager 532.Equally in accordance with known methods, select based on this user, manager 522 obtains data by forming suitable inquiry such as a kind of sql like language from database 518.Manager 522 these inquiries of forwarding give database manager 512 to carry out with respect to database 518 then.
As described, can visit various types of data from remote data base 402 in this way, and remain in the local genome database 518.Example comprises sequence data, external (exonic) structure or locator data, splicing variable data, mark structure or locator data, polymorphic data, data of the same clan, protein grouped data of the same clan, path data, interchangeable gene name data, literature enumerated data and annotation data.Also have many other examples.Equally, not available at present, and can visit and as keeping of describing herein in this locality at the genomic data that become available future.The example that is applicable to the remote data base 402 of visiting in the mode of describing at present comprises GenBank, GenBank New, SwissProt, GenPept, DB EST, Unigene, PIR, Prosite, PPAM, Prodom, Blocks, PDB, PDBfinder, EC Enzyme, Kegg Pathway, Kegg Ligand, OMIM, OMIM Map, OMIM Allele, DB SNP and PubMed.Have at present suitable hundreds of other database, so this tabulation only is illustrative.
In addition, local genome database 518 also can replenish with the data that obtain or from the data of being derived (by subscriber service management device 522) by other local data base of database manager 512 services.Especially, though the native product database 514 that illustrates for convenience of description separates with database 518, it can be same database.As selection, a total data in database 514 or a part can be duplicated or addressable from database 518.
Example more specifically is provided now, and how subscriber service management device 522 receives and responds request from user 101, to be used for genomic information and to be used for product information and/or order.These examples are described with respect to Fig. 7, Fig. 8 and Fig. 9.
Fig. 7 is a process flow diagram of representing exemplary method, and the embodiment of explanation inlet 400 can respond the request of user to genome or product information by way of example.According to the step 710 of this example, input manager 532 499 receives by user's 101 requests for data from client 410 through the Internet.For example, this request can comprise a HTML or XML file, and it comprises that some probes are provided with the user's 101 of identifier selection.As described, as an infinite example, it can be numeral, title, access numbering, symbol, diagrammatic representation or nucleotide or other sequence that this probe is provided with identifier.In some cases, user 101 can carry out this selection by utilizing one or more analysis application 199A, to select probe identifier to be set (for example, draw a ring that centers on point as mentioned above), activate by various known methods then and enter the mouth 400 communicate by letter, such as right-click mouse.According to various known methods, this request can stipulate that also user 101 is whether interested in the type details of genome and/or product data and desired data.For example, user 101 can select the title or the like of classification, the seller or the product of product from drop-down menu.As mentioned above, manager 532 provides user 101 request to subscriber service management device 522.
According to step 720, subscriber service management device 522 starts user 101 identification.Fig. 8 is a block scheme that more provides to details the functional unit of manager 522, comprises account ID determiner 822, and it carries out the task of identifying user 101 in this illustrative embodiment.Determiner 822 can utilize any known method to go to obtain this information, such as using the cookies technology or extracting from the user's request by the identification number of user's input.By database manager 512, determiner 810 can compare user ID and the clauses and subclauses in user account database 513 with further identifying user 101.In another embodiment, as mentioned above,, need not obtain user 101 sign though can write down statistics or the information relevant with user 101 request.
According to step 725, subscriber service management device 522 is worked out a suitable inquiry (for example, the use sql like language version) probe that is used for being correlated with identifier and corresponding gene or EST is set.Gene or EST determiner 820 are functional units of exemplarily carrying out the manager 522 of this operation task.Determiner 820 is transmitted this inquiry and is given database manager 512.If the probe that is provided by user 101 is provided with identifier and comprises sequence information, this inquiry can be from database 511 so, and/or from the SIF information database 516, seek, the sequence that the identification of one or more probe settings has corresponding (for example, being similar to the biology implication).If being provided with identifier, this probe (for example comprises title or number, insert numbering), this inquiry can be sought the sign that this probe is provided with from database 516 so, as described, comprise with title, number and other probes the relevant data of identifier are set corresponding to gene or EST.User 101 also can adopt database application 230 to go to obtain this information in this locality, and in accordance with known methods, comprises it in this information request.In this case, need not implementation step 725.
As in step 730 expression, subscriber service management device 522 is then used genomic information and/or product information be correlated with represented gene and/or EST.The execution of this operation task is undertaken by correlator 830 in illustrational example.In of many possible embodiment, correlator 830 is worked out an inquiry and is arrived database 513 via database manager 512, so that obtain the suitable information that is connected in native product database 514 and/or local genome database 518.Fig. 9 is the diagrammatic representation that a database 513 is simplified.Those this areas those skilled in the art will be understood that, this expression provides for clearly demonstrating purpose, and many other embodiment are possible.In aspect of the suitable inquiry of database 513, in order to illustrate that supposition is a relational database, gene or EST insert numbering 902 to probe ID 912 to be set relevant with linking 904.As representing that at Fig. 9 by two ID 902A and 902B are related to same link 904N, it is relevant that a plurality of genes and/or EST can be provided with ID with same probe.The information that provides at database 516 as mentioned above is provided the info class that is used for setting up this correlationship, and therefore this link can be used database 516 to pre-determine or dynamically determine.
In another embodiment, correlator 830 simple relevant one or more genes or EST identifiers are such as inserting the product of numbering with such as biological products.These embodiment are by representing up to the arrow of correlator 830 from determiner 810 (it is selectable) footpath in Fig. 8.Should relevant can realize, such as by providing an inquiry to native product database 514, to long-range homepage 404 and/or remote data base 402 according to the classic method of any kind of.These inquiries can for example, be tabled look-up in check by the seller's index or the keying of classification, type, title or product, may be appropriate in relational database or other the data structure.In addition, according to the method known to those those of ordinary skill in the related art, this inquiry can searching products, product web page, perhaps the product data source of other relevant with gene or EST identifier in logic or on the sentence structure.The result of this inquiry can offer user 101 by output manager 534 then, such as 499 offering client 410 through the Internet.
Along with the suitable link 904 that ID912 is set to probe, can obtain to be linked to one or more links 916 of relevant product and/or genomic data.For example, link 904N can be linked to probe 912C is set, and it is that to arrive relevant product and/or genomic data related with link 916C.Being used to set up this relevant information can be analyzed (for example, statistics and/or by an adaptive system, such as nervous system network) by the inquiry essence that the user carries out based on specialty input and/or computing machine and pre-determine.For example, can observe or expect that the experiment of (as described, by artificial or computing machine) user's guiding gene expression formula causes discerning certain gene and may wish to use the antibody for this gene to go to continue the experiment of control protein level.Relation between gene and suitable antibody can be stored in the suitable data storehouse, and for example database 516.Therefore link the link that 916C can be included in product or genomic data identifier, its identification about suitable antibody (for example, the link of the data link to product/genome ID922A), (for example discern general antibody directory link, ID922B), perhaps discerning the probe array that clearly is designed for the joint form gene that detects another interest links (for example, ID922C).For illustrative purposes, especially in this example, suppose that link 916C leads to ID922C.Can pre-determine by the content of link 926 about the information that engages variable probe array availability.For example, the link 926D (as shown, with ID922C relation being arranged) that can store the Internet and/or database query URL leads to seller's webpage, native product database 514 and/or local genome database 518.Equally, the content of link 926D can by database 514 or 518 or remote data base such as database 402 or webpage 404 dynamically determine.These handle and similarly handle step 735 expression by Fig. 7.
Those skilled in the art will appreciate that as those this illustrative arrangement of database 513 may have the embodiment of a lot of changes and variation.For example, probe is provided with identification data can be linked to array identifier (such as array ID914), and it can be with to link 916 relevant then.As a lot of possible examples another, gene or EST insert numbering can directly be linked to product and/or genomic data ID922, perhaps, even directly arrives and links 926.For example the enforcement of example is offered an opportunity based on narrower inquiry by the user and is used to carry out association on a large scale.For example, the user can only select a probe that identifier is set, but identifier can be linked to the data of multiple gene and/or ETS, and it can also be linked to a plurality of products or genomic data.In another example, link 926D can comprise a link to local genome database 518.Based on probe identifier, gene or EST are set and insert the data that numbering, sequence information or other the inquiry by user 101 provide or release, database 518 can be according to known inquiry and/or the relevant data of retrieval technique retrieval.
Turn back to Fig. 7 now, especially step 740, the essence that the data of returning according to the inquiry that is had by correlator 830 are used as the suitable data of returning offers product data processor 842, genomic data processor 844, perhaps both.This be convenient to explanation, processor 842 and 844 functional separation illustrate, but there is no need so to do. Processor 842 and 844 all known introductions of application or data transferring technique are to prepare graphical user interface, the file that is used to transmit and the data of other form.The data that to handle like this offer output manager 534 then, are used to send to client 410.
In certain embodiments, user 101 can be to this data response that sends by representing hope purchase product or reception more information.The request that is used to ask for further information can be handled in the aforesaid mode that is similar to Fig. 7.If user 101 expresses the requirement of wishing to buy product (referring to identifying unit 745), the product of this expression can be prepared shipment or other processing, and implement the method for ecommerce according to known being used to, can adjust this user's account.As one of many selective embodiment, subscriber service management device 522 can be notified the order of product seller user 101, and this seller can shipping or order the shipment of this batch product.In aspect of this embodiment, manager 522 can illustrate that then expense should be from the seller's charge that is used to introduce.
In some embodiment of inlet 400, user 101 can offer inlet 400 (for example, via client 410, the Internet 499 and input manager 532) one or more genes or EST rising number or other gene or EST identifiers.Alternatively, perhaps in addition, user 101 can offer inlet 400 one or more probes identifier is set.User 101 can be from public resource, carry out the result of test prod array from sign user 101 conduct, perhaps from have the series of genes or the EST of corresponding probe at probe array, perhaps from arbitrarily other resource or obtain gene, EST and/or probe groups identifier in other mode arbitrarily.Input manager 532 receives one or more genes, EST or probe groups identifier, and offers subscriber service management device 522 with it or they, and it is worked out an inquiry and gives database manager 512.According to known method for inquiring and form, this inquiry is from being provided with the native product database 514 searching information of the relevant product information of identifier with gene, EST and/or probe.For this purpose, native product database 514 based on or keying on any one or more genes, EST and/or probe groups identifier can index or can search product.In accordance with known methods, some embodiment can comprise with gene, EST or probe identifier similarity coupling is set, if for example submitted the whole or a part of of gene, EST, SFI (corresponding to this probe groups identifier) sequence to.Equally, in accordance with known methods such as tabling look-up, can implement title annexation function, the form that makes selective title or gene, EST or probe that identifier is set can find, and uses in the product data inquiry.In addition, in certain embodiments, according to known Internet search technology, manager 522 can start the teledata retrieval of remote data base 402 and/or long-range seller's webpage 404 to obtain product information from remote source.These search can be based on for example product classification or the seller, and this product classification in native product database 514 with product, classification is relevant or the seller and gene, EST or by the probe that user 101 provides identifier to be set relevant.Manager 522 can provide the product data corresponding to gene, EST and/or probe groups identifier, from native product database 514 and/or long-range page or leaf or database 404 or 402, obtain product data, and these product data are offered user 101 via output manager 534.For example, these product data may be included in the webpage 524.In certain embodiments, inlet 400 provides one to be used to provide product data, the system of typical biological products data.This system comprises: input manager 532, and it receives one or more genes, EST and/or probe groups identifier from user 101; Subscriber service management device 522, it comes related gene, EST and/or probe that identifier is set with one or more product data, and make (for example, via database manager 512) product data or for example from local data base 514 or for example remotely obtain in certain embodiments from homepage 404 or database 402; And output manager 534, it offers user 101 with these product data.
Similarly, provide a kind of method that the biological products data are provided, this method comprises step: receive one or more genes, EST and/or probe from user 101 identifier is set; With one or more product data related genes, EST and/or probe groups identifier; Product data are obtained from local (for example database 514) or from far-end (for example homepage 404 or database 402); And these product data offer user 101.
As noted above, the functional unit of inlet 400 can be realized with hardware, software, routine package or its combination in any.In aforesaid embodiment, the function of supposition inlet 400 realizes with software usually for convenience's sake.That is, the functional unit of illustrational embodiment comprises the software instruction device, so that go to carry out the function of description.These software instructions can be with the programming of any programming language, such as Java, Perl, C++, other high-level programming language, low-level language with and combination in any.Therefore 400 the functional unit of entering the mouth can be called executions " one group of genome Web portal instruction ", with and functional unit can be described to the device that instructs by server 510,520 and the 530 genome web portals of carrying out similarly.
In certain embodiments, computer program is described to comprise the medium that the computing machine with steering logic (computer software programs comprise program code) of storage thereon can be used.When being carried out by processor, this steering logic makes processor go to be implemented in the function of inlet 400 described herein.In another embodiment, for example, some above-mentioned function mainly is to implement in the computer hardware that uses the computer hardware state machine.The realization of computer hardware state machine makes that being implemented in function described herein is conspicuous with the technician to relevant field.
Various embodiment and embodiment have been described, should be conspicuous for those those skilled in the relevant art, the foregoing description that has only presented by way of example is illustrative, rather than determinate.Many other the schemes that are used among the various functional units of illustrational embodiment distribution function are possible.The function of any unit can be carried out in the multiple mode in alternatives embodiment.Equally, in alternatives embodiment, the function of plurality of units can be carried out by less or individual unit.
For example, for the sake of clarity, the function of subscriber service management device 522 is used as by describing in the enforcement of the functional unit shown in Fig. 8.But manager 522 there is no need to be divided into these or other different functional unit.Similarly, the operation of the specific functional unit of describing respectively for convenience's sake there is no need to carry out respectively.For example, some of product data processor 842 or repertoire can be implemented by genomic data processor 844, and vice versa.Similarly, in certain embodiments, all functional units can be carried out operations still less or different with respect to the embodiment that illustrational embodiment describes than those.Equally, in a certain embodiments, for the functional unit that illustrates for the purpose of the explanation clearly may be incorporated in other the functional unit.
For example, processor 842 and 844 function can be attributed to the individual feature unit.Similarly, some of database manager 512 or repertoire can be carried out by subscriber service management device 522 and/or by input manager 532.
Also have, this function sequence or partial function can change usually.For example, the function of account ID determiner 810 can be carried out after user data processor 840.Thereby data traffic in this in Fig. 8 and control only are exemplary.Similarly, there is no need always to carry out at the method step shown in Fig. 7 according to the order of the illustrative example suggestion of those figure.For example, identification user's method step 720 can be carried out after step 725,730 or 735.
Some functional unit, file, data structure or the like can be as being arranged in the system storage 120 of computing machine 100 or describing at server 510,520 or 530 usually in illustrational embodiment.But in other embodiment, they can be positioned at or be distributed in computer system or other platform, and it is located and/or away from each other mutually.For example, locate mutually in one or more data files shown in Fig. 5 or data structure 511,513,514,516 or 518, and " be confined to " server 510, can be arranged in computer system or away from the system of server 510.In these cases, can transmit data and/or control to or carry out through network or known being used to by any numerous other with respect to the operation of the database manager 512 of these data files or data structure from the device of remote location.
In addition, those those skilled in the relevant art will understand, between functional unit and the various data structure and among control and data stream can from aforesaid control and data stream, change in many methods.Especially, intermediate function unit (not shown) is control data stream directly, and the function of various unit can make up, decomposes or resequence and goes the reason that allows parallel processing or be used for other.Equally, intermediate data structure or file can use, and the data structure of various descriptions or file can make up or arrange.Therefore a lot of other embodiment and improving all drop on by claims with and the scope of the present invention of equivalent stipulative definition within.

Claims (43)

1. system, be used to provide the data of relevant one or more genes or expressed sequence tag, wherein each gene or expressed sequence tag have the corresponding probe setting that the identifier sign is set by probe at least, and can the detection of biological molecule, comprising:
Constitute input manager, and be set to receive the selection that one or more probes of first group are provided with identifier from the user;
Constitute the gene determinant, and be set to discern one or more gene or expressed sequence tag that group is set corresponding to the probe that the identifier sign is set by first group of probe of first group;
Constitute correlator, and be set to one or more data of first group relevant with first group gene or expressed sequence tag; With
Constitute output manager, and be set to first group of data offered the user.
2. the system of claim 1, wherein:
First group of probe is provided with the probe that identifier identification can detect the biomolecule that comprises nucleic acid group is set.
3. the system of claim 1, wherein:
First group of probe is provided with the probe that identifier identification can detect the biomolecule that the mRNA that comprises corresponding gene transcribes group is set.
4. the system of claim 1, wherein:
First group of probe is provided with the probe that one or more probes of second group all or part that identifier comprises the expression formula that can detect their corresponding gene or expressed sequence tag or differential expression are provided with group identifier is set.
5. the system of claim 4, wherein:
The probe that identifier sign is set by second group of probe is provided with group and is positioned on one or more probe arrays.
6. the system of claim 5, wherein:
The probe that identifier sign is set by second group of probe is provided with group and comprises synthetic on the spot oligonucleotide.
7. the system of claim 6, wherein:
Probe array comprises a probe array that comprises oligonucleotide probes.
8. the system of claim 5, wherein:
At least one probe that identifier sign is set by second group of probe is provided with group and is made up of the single point on the probe array of point-like.
9. the system of claim 5, wherein:
Probe array comprises a point-like array.
10. the system of claim 9, wherein:
The point of at least one point-like array comprises oligonucleotide.
11. the system of claim 1, wherein:
Described user comprise the long-distance user and
Input manager is through network receiving remote user's selection.
12. the system of claim 11, wherein:
Described network comprises the Internet.
13. the system of claim 1, wherein:
At least the first probe that first group of probe is provided with identifier is provided with identifier and comprises the genetic identifier that the gene of identifier is set corresponding to first probe.
14. the system of claim 13, wherein:
Genetic identifier comprises that is inserted a numbering.
15. the system of claim 1, wherein:
The user selects first group of probe that identifier is set, this is to the indication based on the grade of the expression formula of gene or expressed sequence tag or differential expression of small part, and this gene or expressed sequence tag are provided with group corresponding to the probe that the identifier sign is set by first group of probe.
16. the system of claim 1, wherein:
One or more data of first group comprise relevant availability, price, composition, applicability, or one or any combination of the product data of order.
17. the system of claim 16, wherein:
One or more data of first group comprise the product data about biological plant or material, perhaps can be used for the reagent of a biological plant or material.
18. the system of claim 17, wherein:
Equipment, material, or reagent comprises oligonucleotide, probe array, nucleotide clone, antibody, or one or any combination of protein.
19. the system of claim 1, wherein:
Be stored in the data in the native product database one or more data of first group to comprising of small part.
20. the system of claim 19, wherein:
One or more data of first group comprise the link of the seller's that at least one arrives the expression biologics teledata.
21. a system is used to provide the product data about one or more genes or expressed sequence tag, comprising:
Constitute input manager, and be set to receive one or more genes or expressed sequence tag identifier;
Constitute correlator, and be set to one or more product data relevant with gene or expressed sequence tag identifier; With
Constitute output manager, and be set to product data are provided to the user.
22. the system of claim 21, wherein: described product data are biologics data.
23. the system of claim 21, wherein:
Described gene or expressed sequence tag identifier comprise that gene or expressed sequence tag insert numbering.
24. method, be used to provide the data of relevant one or more genes or expressed sequence tag, wherein each gene or expressed sequence tag have the corresponding probe setting that the identifier sign is set by probe at least, with can detect a kind of biomolecule, it comprises the following steps:
Input manager receives the selection that one or more probes of first group are provided with identifier from the user;
The identification of gene determinant is provided with first group one or more genes or expressed sequence tag of group corresponding to the probe that the identifier sign is set by first group of probe;
Correlator is relevant with first group gene or expressed sequence tag with one or more data of first group; With
Output manager offers the user with first group of data.
25. the method for claim 24, wherein
First group of probe is provided with the probe that identifier identification can detect the biomolecule that comprises nucleoprotein acid group is set.
26. the method for claim 24, wherein:
First group of probe is provided with the probe that identifier identification can detect the biomolecule that the mRNA that comprises corresponding gene transcribes group is set.
27. one kind is used to provide the method about the product data of one or more genes or expressed sequence tag, these product data are provided by the system that comprises input manager, correlator and output manager, and this method comprises:
Receive one or more genes or expressed sequence tag identifier by input manager;
By correlator that one or more product data are relevant with gene or expressed sequence tag identifier; With
Output manager offers the user with product data.
28. the method for claim 27, it is applicable to request or order that processing receives from the user by network.
29. the method for claim 28, this method comprise that identification is provided with one or more genes of identifier or first group of expressed sequence tag corresponding to probe that can the detection of biological molecule.
30. the method for claim 29, wherein the user selects one or more probes that first group of identifier is set, and provides the first set product data to the user by one or more webpages.
31. the method for claim 30, wherein:
In first group, probe is provided with the probe that identifier identification can detect the biomolecule that comprises nucleic acid group is set.
32. the method for claim 30, wherein:
In first group, probe is provided with the probe that identifier identification can detect the biomolecule that the mRNA that comprises corresponding gene transcribes group is set.
33. the method for claim 30 further comprises step:
Based on the part first set product data that are provided to the user, second user who receives one or more purchase products by network selects.
34. the method for claim 33 further comprises step:
Identification corresponding to account of user and
To small part based on the product price data of selecting corresponding to second user, adjust account corresponding to the user.
35. the method for claim 33 further comprises step:
Second user's selective selling product based on product is given the user.
36. the method for claim 30, wherein the user carries out at least one gene expression experiment about probe array, to select described probe identifier is set.
37. the method for claim 30, wherein the user selects first group of probe that identifier is set based on the indication corresponding to the degree of the expression of the gene of the probe groups that identifier sign is set by first group of probe or expressed sequence tag.
38. the method for claim 30, wherein:
At least one probe that identifier sign is set by first group of probe is provided with group and is positioned on one or more probe arrays.
39. the method for claim 30, wherein:
Described product data are to select from the group of the product data that comprise relevant availability, composition, applicability and order.
40. the method for claim 30, wherein:
Described product data are from comprising about biological plant or material, can be used for perhaps that the group of product data of a kind of reagent of biological plant or material selects.
41. the method for claim 30, wherein:
Described product data are to select from comprise the group with oligonucleotide, probe array, nucleotide clone, antibody or the relevant product data of protein.
42. the method for claim 30, wherein:
These product data are relevant with PCR primer and/or PCR probe.
43. the method for claim 30, wherein these product data comprise the link of the seller's that at least one arrives the expression biologics teledata.
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