深圳中恒华发股份有限公司.pptx
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1、Lecture 4.11Protein InteractionsMichel DumontierBlueprint Initiativemjdumontblueprint.org http:/blueprint.org Lecture 4.12OutlineMolecular interactionsDiscoveryExperimentalComputationalStorageData MiningFuture DirectionsLecture 4.13Molecular InteractionsBetween two molecular objectsDNA,RNA,gene,prot
2、ein,molecular complex,small molecule,photonBinding SitesUnder an Experimental ConditionWith a particular Cellular LocationPossibly causing some Chemical ActionBALecture 4.14Interaction DiscoveryExpression,Interaction Data,Function,Protein modificationsMicroarrayTwo-HybridMassSpectrometryGeneticsLect
3、ure 4.15A measure of confidence?How do you know if the interaction really exists?Each method has its advantages and disadvantages.Be aware of systematic errors(i.e.tag effects)Be aware of contaminating proteins.Each method observes interactions from a slightly different experimental condition.Suppor
4、t from many different sources is certainly better than just one.Lecture 4.16High-throughput Mass Spectrometric Protein Complex Identification(HMS-PCI)Ste12Ho et al.Nature.2002 Jan 10;415(6868):180-3Mike Tyers,SLRILecture 4.17FilteringRemove promiscuously binding proteins:Proteins identified by MS in
5、 control lanesProteins that were found at a high frequency in the overall experimentKnown high-abundant proteins ribosomal elementsLecture 4.19Synthetic Genetic InteractionsSynthetic genetic interactions(lethal,slow growth)Mate two mutants without phenotypes to get a daughter cell with a phenotypeSy
6、nthetic lethal(SL),slow growthrobotic mating using the yeast deletion libraryGenetic interactions provide functional data on protein interactions or redundant genesAbout 23%of known SLs(1295-YPD+MIPS)are known protein interactions in yeastTong et al.Science.2001 Dec 14;294(5550):2364-8Lecture 4.110W
7、orking overtimeCharlie Boones RobotsCell PolarityCell Wall Maintenance Cell StructureMitosisChromosome StructureDNA Synthesis DNA RepairUnknownOthersSynthetic Genetic Interactions in YeastTong,BooneLecture 4.112PreBIND Literature MiningPreBIND is a data mining tool that helps researchers locate biom
8、olecular interaction information in the scientific literature.Start with a protein name or accession find abstracts with significant interaction information.Ranked list of potential interactors based on the number of high-scoring abstracts found and SVM score.Information is only available for yeast,
9、mouse and human proteins described by NCBI RefSeq identifiersDonaldson et al.PreBIND and Textomy-mining the biomedical literature for protein-protein interactions using a support vector machine.BMC Bioinformatics.2003 Mar 27;4(1):11.Lecture 4.113Search PreBIND with“Chk1”Lecture 4.114View Possible In
10、teractionsLecture 4.115View the abstractLecture 4.116Lecture 4.117Confirm and submit a BIND InteractionLecture 4.118Computational Interaction PredictionBy HomologyIf A and B interact andC is homologous to A and D is homologous to BDo C and D interact?Transitive property They may,ifC&D are from the s
11、ame species unless host-pathogen interactionBinding surface is conservednote domain interactionsBinding residues are conserved Localize to the same cellular compartmentLecture 4.119OutlineMolecular interactionsDiscoveryStorageDatabasesFile FormatsData MiningFuture DirectionsLecture 4.120Information
12、ScopeDBEvolutionary BiologyBiochemistryClinical StudiesChemistryBiophysicsBioinformaticsPharmacologyPopulation BiologyProteomicsEpidemiologyMolecular BiologyImmunologyGenomicsGeneticsLecture 4.121A free,open-source database for archiving and exchanging molecular assembly information.BIND is managed
13、by the Blueprint Initiative at Mount Sinai Hospital in Toronto.The database contains Interactions/ReactionsMolecular complexesPathwaysBIND has an extensive data model,GNU software tools and is based on the NCBI toolkit;extended recently to XML/JavaThe 97000 BIND records are curated and validated.htt
14、p:/bind.caBader GD,Betel D,Hogue CW.(2003)BIND:the Biomolecular Interaction Network Database.Nucleic Acids Res.31(1):248-50 PMID:12519993 Lecture 4.122Browse Interface(v2.5)Lecture 4.123BIND Submit Record View(v3.0)Lecture 4.124Publication LinksLecture 4.125OntoglyphsLecture 4.126Gene OntologyFuncti
15、onal protein annotationhttp:/www.geneontology.org Controlled vocabulary for protein function and localizationMolecular function e.g.DNA helicaseBiological process e.g.mitosisCellular Component e.g.nucleusLecture 4.127BIND Interaction Viewer 3.0Lecture 4.128Database of Interacting Proteins(DIP)The DI
16、P database catalogs experimentally determined interactions between proteins.It combines information from a variety of sources to create a single,consistent set of protein-protein interactions.The data stored within the DIP database were curated,both,manually by expert curators and also automatically
17、 using computational approaches that utilize knowledge about the protein-protein interaction networks extracted from the most reliable,core subset of the DIP data.44349 interactions from 107 organisms involving 17048 proteinsSalwinski L,Miller CS,Smith AJ,Pettit FK,Bowie JU,Eisenberg D(2004)The Data
18、base of Interacting Proteins:2004 update.NAR 32 Database issue:D449-51http:/dip.doe-mbi.ucla.eduCopyright 1999-2003 UCLAThe DIP database is the property of the Regents of the University of California.It is forbidden to redistribute,derivatize,or encapsulate the DIP in another database without permis
19、sion from UCLA and David Eisenberg.Lecture 4.129DIP Search InterfaceLecture 4.130MINTMINT database v3.0.MINT is a relational database designed to store interactions between biological molecules.MINT focuses on experimentally verified protein interactions with special emphasis on proteomes from mamma
20、lian organisms.MINT consists of entries mined in the scientific literature by curators.The curated data can be analyzed in the context of the high throughput data and viewed graphically through the MINT Viewer.42534 Interactions with 18148 proteinsZanzoni A.,Montecchi-Palazzi L.,Quondam M.,Ausiello
21、G.,Helmer-Citterich M.and Cesareni G.MINT:a Molecular INTeraction database.(2002)FEBS Letters,513(1);135-140.http:/mint.bio.uniroma2.it/mint Lecture 4.131MINT Record ViewLecture 4.132MINT Interaction ViewerLecture 4.133Other Interaction DatabasesMIPShttp:/mips.gsf.de/proj/yeast/tables/interaction/In
22、tAct EBIs interaction databasehttp:/www.ebi.ac.uk/intact/Human Protein Interaction Databasehttp:/www.hpid.org/TRANSFAC transcription factorshttp:/www.gene- Repository for Interaction Sets(GRID)http:/biodata.mshri.on.ca/grid/servlet/IndexLecture 4.134Data Exchange File FormatsBIND http:/bind.ca Peer
23、reviewed but closed process(Spec v3.1)ASN.1 or XML DTD/SchemaPSI-MI http:/ Peer reviewed,HUPO community standardWidely adoptedBioPax http:/www.biopax.org Community schema(Sloan Kettering,BioPathways Consortium)XML Schema,OWL,Protg and GKBSBMLWidely adopted for representing models of biochemical reac
24、tion networksLecture 4.135BINDASN.1(text)XMLFlat FileLecture 4.136MINT PSI level 1Lecture 4.137PSI Record FormatLecture 4.138BioPAXCollaborative effort to create a data exchange format for biological pathway data http:/www.biopax.org Lecture 4.139OutlineMolecular interactionsDiscoveryStorageData Min
25、ingGraph TheoryComparisonsVisualization ToolsFuture DirectionsLecture 4.140Integrated Data MiningDetermine new relationships between data.Identify non-obvious patternsStatistical clustering(e.g.microarray)Graph theoryLecture 4.141Graph TheoryVertex(node)EdgeCycle-5Directed Edge(Arc)Weighted Edge710W
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