淀粉样变性病讲解PPT课件.ppt

AFieldGuidepart2 GenomeresourcesSequencesimilarity Apr 2007 ShandongUniversity 1 GenomeResources LocusLink Genedatabase UniGene TraceArchive MapViewer Homologene 2 GenomicBiology 3 4 5 6 GenomeProjects microb 7 8 9 GenomeResources LocusLink Genedatabase UniGene TraceArchive MapViewer Homologene 10 Asinglequeryinterfaceto Sequences RefSeqs GenBank HomologeneMaps MapViewerEntrezlinks LocusLink LocusLinkwillbereplacedbyEntrezGeneonMARCH1 2005 CheckGeneFAQforcurrentinformation 11 EntrezGene LocusLink Asinglequeryinterfaceto Sequences RefSeqs GenBank HomologeneMaps MapViewerEntrezlinks EntrezGene Moreorganisms allRefSeqgenomesEntrezintegration 12 Gsn sym 淀粉样变性病 13 14 GlobalEntrez NADH2 nadh2 47 15 EntrezGene NADH2 26records 16 GeneRecordforPongoNADH2 17 DisplayExons Introns GeneTable 18 GeneTable 19 ARecordWithMoreData HumanHFE 血色沉着病 20 GeneGraphicLinks 21 Introns Exons GeneTable linkstosequence 22 ARecordWithMoreData HumanHFE 23 EntrezSNP hfe genename ANDhuman orgn 52 血色沉着病 24 LinkingtoSNP 染色体定位 基因定位 序列定位 25 SNPinStructure 26 LinktoOMIM 27 VariantsinOMIM 28 GenomeResources LocusLink Genedatabase TraceArchive MapViewer Homologene UniGene 29 Gene orientedclustersofexpressedsequences AutomaticclusteringusingMegaBlastEachclusterrepresentsauniquegeneInformedbygenomehitsInformationontissuetypesandmaplocationsUsefulforgenediscoveryandselectionofmappingreagents UniGene 30 AClusterofESTs query 5 ESThits 3 ESThits 31 Unigene 32 UniGeneCollections 33 ExampleUniGeneCluster 34 HistogramofclustersizesforUniGeneHsbuild177 35 UniGeneClusterHs 95351 36 UniGeneClusterHs 95351 37 UniGeneClusterHs 95351 expression 38 UniGeneClusterHs 95351 seqs 39 Downloadsequences webpage ftpsite 40 GenomeResources LocusLink Genedatabase UniGene TraceArchive MapViewer Homologene 41 TheNewHomologene Automateddetectionofhomologsamongtheannotatedgenesofcompletelysequencedeukaryoticgenomes NolongerUniGenebasedProteinsimilaritiesfirstGuidedbytaxonomictreeIncludesorthologsandparalogs 42 Orthologs和Paralogs是同源序列的两种类型 Orthologs 垂直同源基因 是指来自于不同物种的由垂直家系 物种形成 进化而来的蛋白 并且典型的保留与原始蛋白有相同的功能 Paralogs 平行同源基因 是那些在一定物种中的来源于基因复制的蛋白 可能会进化出新的与原来有关的功能 请参考文献获得更多的信息 43 geneduplication ParalogsvsOrthologs earlyglobingene A chaingeneB chaingene paralogs orthologsorthologs 44 TheNewHomologene 45 RAG1 Homologene rag1 12 recombinationactivatinggene 46 RAG1 Homolgene RAG1 Amniota 47 Homolgene RAG1 48 49 Homolgene RAG1 50 GenomeResources LocusLink Genedatabase UniGene TraceArchive MapViewer Homologene 51 52 53 54 MapViewer 55 ListView 56 HumanMapViewer 腺甙脱氨酶 57 MapViewer HumanADAR 4 58 MVHsADAR 59 Maps Options Sequencemaps AbinitioAssemblyRepeatsBES CloneCloneNCI CloneContigComponentCpGislanddbSNPhaplotypeFosmidGenBank DNAGenePhenotypeSAGE TagSTSTCAG RNATranscript RNA Hs UniGeneHs EST Cytogeneticmaps IdeogramFISHCloneGene CytogeneticMitelmanBreakpointMorbid Disease GeneticMaps deCODEGenethonMarshfield RHmaps GeneMap99 G3GeneMap99 GB4NCBIRHStandford G3TNGWhitehead RHWhitehead YAC Mm UniGeneMm ESTRn UniGeneRn ESTSsc UniGeneSsc ESTBt UniGeneBt ESTGga UniGeneGga ESTVariation Maps Options 60 MapViewer UniGene Component Repeats Gene 61 Mastermap repeats 62 Gene Phenotype Variation 63 Maps Options Maps Options 64 GenomeResources LocusLink Genedatabase UniGene TraceArchive MapViewer Homologene 65 66 67 2019 12 29 68 StrongylocentrotuspurpuratusTraces 69 BLAST BasicLocalAlignmentSearchTool 70 WebAccess BLAST VAST Entrez Text Sequence Structure 71 72 BasicLocalAlignmentSearchTool Whyusesequencesimilarity BLASTalgorithmBLASTstatisticsBLASToutputExamples 73 WhyDoWeNeedSequenceSimilaritySearching ToidentifyandannotatesequencesToevaluateevolutionaryrelationshipsOther modelgenomicstructure e g Spidey checkprimerspecificityinsilico NCBI stool 74 BLASTWebsiteStats 75 GlobalvsLocalAlignment 76 GlobalvsLocalAlignment Seq1 WHEREISWALTERNOW 16aa Seq2 HEWASHEREBUTNOWISHERE 21aa 77 TheFlavorsofBLAST StandardBLASTtraditional contiguous wordhitpositionindependentscoringnucleotide proteinandtranslations blastn blastp blastx tblastn tblastx MegablastoptimizedforlargebatchsearchescanusediscontiguouswordsPSI BLASTconstructsPSSMsautomatically usesasqueryverysensitiveproteinsearchRPSBLASTsearchesadatabaseofPSSMstoolforconserveddomainsearches 78 WidelyusedsimilaritysearchtoolHeuristicapproachbasedonSmithWatermanalgorithmFindsbestlocalalignmentsProvidesstatisticalsignificanceAllcombinations DNA Protein queryanddatabase DNAvsDNA blastnDNAtranslationvsProtein blastxProteinvsProtein blastpProteinvsDNAtranslation tblastnDNAtranslationvsDNAtranslation tblastxwww standalone andnetworkclients BasicLocalAlignmentSearchTool 79 TranslatedBLAST Query Database Program ucleotide rotein N N N N P P blastx tblastn tblastx Particularlyusefulfornucleotidesequenceswithoutproteinannotations suchasESTsorgenomicDNA 80 HowBLASTWorks Makelookuptableof words forqueryScandatabaseforhitsUngappedextensionsofhits initialHSPs Gappedextensions notraceback Gappedextensions traceback alignmentdetails 81 NucleotideWords GTACTGGACATTACTGGACATGACTGGACATGGCTGGACATGGATGGACATGGACGGACATGGACCGACATGGACCCACATGGACCCT Makealookuptableofwords 82 ProteinWords GTQTQIQITITVTVEVEDEDLDLF Makealookuptableofwords f11 blastpdefault 83 MinimumRequirementsforaHit NucleotideBLASTrequiresoneexactmatchProteinBLASTrequirestwoneighboringmatcheswithin40aa GTQITVEDLFYNISEIYYN ATCGCCATGCTTAATTGGGCTTCATGCTTAATT neighborhoodwords oneexactmatch twomatches A40 blastpdefault 84 BLASTPSummary High scoringpair HSP 85 ScoringSystems Nucleotides AGCTA 1 3 3 3G 3 1 3 3C 3 3 1 3T 3 3 3 1 Identitymatrix CAGGTAGCAAGCTTGCATGTCA rawscore 19 9 10CACGTAGCAAGCTTG GTGTCA r1 q 3 86 ScoringSystems Proteins PositionIndependentMatricesPAMMatrices PercentAcceptedMutation Derivedfromobservation smalldatasetofalignmentsImplicitmodelofevolutionAllcalculatedfromPAM1PAM250widelyusedBLOSUMMatrices BLOckSUbstitutionMatrices Derivedfromobservation largedatasetofhighlyconservedblocksEachmatrixderivedseparatelyfromblockswithadefinedpercentidentitycutoffBLOSUM62 defaultmatrixforBLASTPositionSpecificScoreMatrices PSSMs PSI andRPS BLAST 87 A4R 15N 206D 2 216C0 3 3 39Q 1100 35E 1002 425G0 20 1 3 2 26H 201 1 300 28I 1 3 3 3 1 3 3 4 34L 1 2 3 4 1 2 3 4 324K 120 1 311 2 1 3 25M 1 1 2 3 10 2 3 212 15F 2 3 3 3 2 3 3 3 100 306P 1 2 2 1 3 1 1 2 2 3 3 1 2 47S1 110 1000 1 2 20 1 2 14T0 10 1 1 1 1 2 2 1 1 1 1 2 115W 3 3 4 4 2 2 3 2 2 3 2 3 11 4 3 211Y 2 2 2 3 2 1 2 32 1 1 2 13 3 2 227V0 3 3 3 1 2 2 3 331 21 1 2 20 3 14X0 1 1 1 2 1 1 1 1 1 1 1 1 1 200 2 1 1 1ARNDCQEGHILKMFPSTWYVX BLOSUM62 88 Position SpecificScoreMatrix DAF 1 Serine Threonineproteinkinasescatalyticloop 89 ARNDCQEGHILKMFPSTWYV435K 100 1 23030 2 21 1 1 1 1 1 1 1 2436E0102 102 10 1 1000 100 1 1 1437S00 10110110 100020 1 10 1438N 10 1 110 133 1 11 100 1 111 1439K 211 1 20 1 2 2 1 251 2 2 1 1 2 2 1440P 2 2 2 2 3 2 2 2 2 1 2 10 37 1 2 3 1 1441A3 21 20 101 2 2 20 1 2310 3 30442M 3 4 4 4 3 4 4 5 470 410 4 4 2 4 12443A4 4 4 40 4 4 3 44 1 4 2 3 4 1 2 4 34444H 4 2 1 3 5 2 2 410 6 5 3 4 3 2 3 4 50 5445R 48 3 40 1 2 3 2 5 40 3 2 4 3 30 4 5446D 4 4 18 6 20 3 3 5 6 3 5 6 4 2 3 7 5 5447I 4 5 6 6 3 4 5 6 535 511 5 5 3 4 31448K001 3 5 1 1 3 3 5 57 4 5 3 1 2 5 4 4449S0 3 2 30 2 2 3 3 4 4 2 4 5262 5 4 4450K0301 500 4 1 4 34 3 221 1 5 4 4451N 4 38 1 5 2 2 3 1 6 6 2 4 5 4 1 2 6 4 5452I 3 5 5 60 5 5 6 562 52 2 5 4 3 5 33453M 4 4 6 6 3 4 5 6 506 510 5 4 3 4 30454V 3 3 5 6 3 4 5 6 533 42 2 5 4 3 5 35455K 2114 50 1 21 4 24 3 2 30 1 5 2 3456N1130 4 110 3 4 43 2 5 22 2 5 4 4457D 3 255 1 11 10 5 40 2 5 10 2 6 4 5458L 3 10 30 3 23 4 23011 2 2 35 1 3 Position SpecificScoreMatrix catalyticloop blastpgp iNP 499868 2 dnr j3 QNP 499868 pssm 90 LocalAlignmentStatistics HighscoresoflocalalignmentsbetweentworandomsequencesfollowtheExtremeValueDistribution Score S Alignments ExpectValueE numberofdatabasehitsyouexpecttofindbychance S yourscore expectednumberofrandomhits Moreinfo www ncbi nlm nih gov BLAST tutorial Altschul 1 html 91 AdvancedBLASTOptions Nucleotide ExampleEntrezQueriesnucleotideall Filter NOTmammalia Organism greenplants Organism biomolmrna Properties gbdivest Properties ANDrat organism OtherAdvanced e10000expectvalue v2000descriptions b2000alignments 92 AdvancedBLASTOptions Protein MatrixSelectionPAM30 moststringentBLOSUM45 leaststringent ExampleEntrezQueriesproteinsall Filter NOTmammalia Organism greenplants Organism srcdbrefseq Properties OtherAdvanced e10000expectvalue v2000descriptions b2000alignments LimitbytaxonMusmusculus Organism Mammalia Organism Viridiplantae Organism 93 sp P27476 NSR1 YEASTNUCLEARLOCALIZATIONSEQUENCEBINDINGPROTEIN P67 Length 414Score 40 2bits 92 Expect 0 013Identities 35 131 26 Positives 56 131 42 Gaps 4 131 3 Query 362STTSLTSSSTSGSSDKVYAHQMVRTDSREQKLDAFLQPLSKPLS SQPQAIVTEDKTD418S SSSS SSS S SSS EKSbjct 29SSSSSESSSSSSSSSESESESESESESSSSSSSSDSESSSSSSSDSESEAETKKEESKDS88 Filtered Unfiltered LowComplexityFiltering 94 OtherBLASTAlgorithms MegablastDiscontiguousMegablastPSI BLASTPHI BLAST 95 Megablast NCBI sGenomeAnnotator LongalignmentsofsimilarDNAsequencesGreedyalgorithmConcatenationofquerysequencesFasterthanblastn lesssensitive 96 MegaBLAST WordSize Trade off sensitivityvsspeed 97 DiscontiguousMegablast UsesdiscontiguouswordmatchesBetterforcross speciescomparisons 98 TemplatesforDiscontiguousWords W 11 t 16 coding 1101101101101101W 11 t 16 non coding 1110010110110111W 12 t 16 coding 1111101101101101W 12 t 16 non coding 1110110110110111W 11 t 18 coding 101101100101101101W 11 t 18 non coding 111010010110010111W 12 t 18 coding 101101101101101101W 12 t 18 non coding 111010110010110111W 11 t 21 coding 100101100101100101101W 11 t 21 non coding 111010010100010010111W 12 t 21 coding 100101101101100101101W 12 t 21 non coding 111010010110010010111 Reference Ma B Tromp J Li M PatternHunter fasterandmoresensitivehomologysearch BioinformaticsMarch 2002 18 3 440 5 W wordsize matchesintemplatet templatelength 99 Discontiguous Cross species MegaBLAST 100 DiscontiguousWordOptions 101 MegaBLASTvsDiscontiguousMegaBLAST NM 017460 HomosapienscytochromeP450 family3 subfamilyA polypeptide4 CYP3A4 transcriptvariant1 mRNA 2768letters vsDrosophila 102 MegaBLASTvsDiscontiguousMegaBLAST MegaBLAST Nosignificantsimilarityfound DiscontiguousmegaBLAST 103 AnotherExample DiscontiguousmegaBLAST numeroushits Query NM 078651DrosophilamelanogasterCG18582 PA mbt mRNA 3244bp note mushroombodiestiny synonyms Pak2 STE20 dPAK2 MegaBLAST Nosignificantsimilarityfound Database nr nt Mammalia orgn 104 Ex DiscontiguousMegaBLAST 105 Ex BLASTN 106 PSI BLAST Example Confirmingrelationshipsofpurinenucleotidemetabolismproteins Position specificIteratedBLAST 107 gi 113340 sp P03958 ADA MOUSEADENOSINEDEAMINASE ADENOSINEMAQTPAFNKPKVELHVHLDGAIKPETILYFGKKRGIALPADTVEELRNIIGMDKPLSLPGFVIAGCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVDPMPWNQTEGDVTPDDVVDEQAFGIKVRSILCCMRHQPSWSLEVLELCKKYNQKTVVAMDLAGDETIEGSSLFPGHVEAYRTVHAGEVGSPEVVREAVDILKTERVGHGYHTIEDEALYNRLLKENMHFEVCPWSSYLTGAVRFKNDKANYSLNTDDPLIFKSTLDTDYQMTKKDMGFTEEEFKRLNINAAKSSFLPEEEKK PSI BLAST 0 005 EvaluecutoffforPSSM 108 RESULTS InitialBLASTP Sameresultsasprotein proteinBLAST differentformat 109 ResultsofFirstPSSMSearch OtherpurinenucleotidemetabolizingenzymesnotfoundbyordinaryBLAST 110 TenthPSSMSearch Convergence Justbelowthreshold anothernucleotidemetabolismenzyme 111 ReversePSI BLAST RPS BLAST 112 Adenosine AMPDeaminaseDomain 113 PHI BLAST gi 231729 sp P30429 CED4 CAEELCELLDEATHPROTEIN4MLCEIECRALSTAHTRLIHDFEPRDALTYLEGKNIFTEDHSELISKMSTRLERIANFLRIYRRQASELIDFFNYNNQSHLADFLEDYIDFAINEPDLLRPVVIAPQFSRQMLDRKLLLGNVPKQMTCYIREYHVIKKLDEMCDLDSFFLFLHGRAGSGKSVIASQALSKSDQLIGINYDSIVWLKDSGTAPKSTFDLFTDILKSEDDLLNFPSVEHVTSVVLKRMICNALIDRPNTLFVFDDVVQEETIRWAQELRLRCLVTTRDVEIASQTCEFIEVTSLEIDECYDFLEAYGMPMPVGEKEEDVLNKTIELSSGNPATLMMFFKSCEPKTFEK GA xxxxGK ST 114 What sNew 115 BLASTDatabases Nucleotiderefseq rna NM XM refseq genomic NC NG env ntenvironmentalsample filter e g 16SrRNAProteinrefseq NP XP env nr 116 NewFormatter Selectlowercase Sel