2000 1999 12 15 115 GenBank DNA 46 5 DNA 535 EST 339 UniGene 7 25 70 2000 1 28 16% 37.7%DNA " "-- 22 1999 12EST (dbEST) SNPs DNARNA( ) RNA DNA DNA2.1Genbank EMBL DDBJ SWISS-PROT PIR PDB GDB TRANSFAC SCOP1. GenbankGenbank (NCBI) EST Genbank (EMBL) DNA (DDBJ) 1999 8 Genbank 460 34 Genbank NCBI FTP NCBI NCBIGenbank 55,000 56% ( 34% EST ) Genbank EST 16 EST(1)GenbankNCBI Entrez Entrez Web Entrez Genbank Genbank (MMDB) PubMed MedlineEntrez Entrez (Limits) (Index) (History) (Clipboard) Entrez(2) GenbankNCBI Genbank Web BankIt SequinBankItGenbank BankIt BankIt EST GSS BankIt BankItSequin Sequin Sequin FASTA ASN.1 Sequin Sequin ftp:///sequin/ SequinNCBI Entrez /entrez/BankIt /BankItSequin /Sequin/2. EMBLEMBL (EBI) Genbank DDBJ Oracal (SRS) EMBL Web WEBIN Sequin/embl/SRS /WEBIN /embl/Submission/webin.html3. DDBJDNA (DDBJ) Genbank EMBL SRS SequinDDBJ http://www.ddbj.nig.ac.jp/4. GDB(GDB) (HGP) GDB GDB ( amplimers PCR breakpoints cytogenetic markers fragile sites EST syndromic regions contigs ) ( content contig )( ) GDB WebGDB GDB /gdb/2.21. PIR PSDPIR (PSD) (PIR) (MIPS) (JIPID) 142,000 ( 99 9 ) 99% PSDPSD PIR BLAST FASTAGeneFINDPIR PSD /ftp:///pir/2. SWISS-PROTSWISS-PROT (EBI) SWISS-PROT 30(SRS) SWISS-PROT EBISWISS-PROT WebSWISS-PROT /swissprot/3. PROSITEPROSITE PROSITE motif PROSITE PROSITE profile profile PROSITEPROSITE http://www.expasy.ch/prosite/4. PDB(PDB) Brookhaven PDB X (NMR) PDB (RCSB) RCSB PDB PDB Rasmol PDBRCSB PDB /pdb/5. SCOP(SCOP) (fold) / SCOP ASTRAIL SCOP PDB-ISLSCOP /scop/6. COG(COGs) 21 COG COGNITOR COGs COG COG COG Web COGNITORCOG /COGCOG COGNITOR ftp:///pub/COG2.31. KEGG(KEGG) GENES PA THW AY KEGGLIGAND KEGG JavaKEGG http://www.genome.ad.jp/kegg/2. DIP(DIP) DIPDIP /3. ASDB(ASDB) ASDB( ) SWISS-PROT ASDB( ) GenbankASDB /asdb4. TRRD(TRRD) TRRD TRRD TRRDGENES( TRRD ) TRRDSITES( ) TRRDFACTORS( TRRD ) TRRDEXP( ) TRRDBIB( ) TRRDTRRD http://wwwmgs.bionet.nsc.ru/mgs/dbases/trrd4/5. TRANSFACTRANSFAC DNA profiles SITE GENE FACTOR CLASS MA TRIX CELLS METHOD REFERENCE TRANSFAC PA THODB S/MART DB TRANSPA TH CYTOMER TRANSFAC WebTRANSFAC http://transfac.gbf.de/TRANSFAC/2.41. DBCatDBCat 500 DNA RNADBCat biogen.fr/services/dbcat/DBCat ftp://biogen.fr/pub/db/dbcat2. PubMedPubMed NCBI MEDLINE Pre-MEDLINE Entrez PubMedPubMed /EMBNetprofile ]3.1motif 30%Needleman-Wunsch Smith-Waterman SIM FASTA LALIGN/ PAM BLOSUM PAM250 BLOSUM62 BLOSUM90 BLOSUM30 BLOSUM90 BLOSUM3010 15 1 2E EGenbank SWISS-PROT FASTA BLAST FASTAFASTA ktup ktup=2 FASTA E FASTABLAST FASTA NCBI Web BLAST BLAST1. BLASTblastpblastnblastx DNA ESTTblastntblastx EST2. BLASTNr SWISS-PROT,PIR,PRF GenBank PDBMonth nr 30Swiss-prot SWISS-PROTPdb PDBYeaste.coliKabat Kabatalu REPBASE Alu3. BLASTNr GenBank EMBL DDBJ PDB EST STS GSS 0,1,2HTGS nr 30Month Nr 30Dbest Genbank EMBL DDBJ PDB ESTDbsts Genbank EMBL DDBJ PDB STSHtgs0,1,2 (3 HTG nr )Yeaste.coliPdbKabat KabatV ector GenbankMitoAlu REPBASE Alugss (Genome Survey Sequence)BLAST FASTA FASTA “> 80IUB/IUPAC “- “U “* ( “N “X”)A C G T U R G A( ) Y T C( ) K G T( ) M A C( ) S G C( ) W A T( )B G TCD G A T HA C T V G C A N A G C T 20B Asp Asn U Z Glu Gln X “*BLAST 2.0 BLAST(PSI-BLAST) PSI-BLAST profile profile profile PSI-BLAST BLAST profile PSI-BLAST BLAST threading PSI-BLAST NCBI BLAST NCBI FTP PSI-BLASTNCBI BLUST /BLAST/BLUST ftp:///blast/FASTA ftp:///pub/fasta/3.2profile CLUSTALW( PC CLUSTALX) CLUSTALWCLUSTALW NCBI FTP CLUSTALW EBI Web CLUSTALW Email CLUSTALW FASTA PIR SWISS-PROT GDE Clustal GCG/MSF RSF ALN GCG PHYLIP GDECLUSTALW “* “.EBI CLUSTALW /clustalw/CLUSTALW ftp:///pub/software/DNA / “ ”104.1DNA DNA DNA DNA “ ” DNA “ ” TA TA Box cDNA EST1.CENSOR RepeatMasker Web Email XBLAST Internet XBLAST Repbase “X”CENSOR Repbase /CENSOR Email censor@RepeatMasker /cgi-bin/RepeatMaskerXBLAST ftp:///pub/jmcRepbase ftp://ncbi//repository/repbase/REF2.EST3.DNA “ ” ( ) ( 3,6,9,... ) / ( )GRAIL GenMark GRAIL WebGRAIL /Grail-1.3/4.5. /NetGene NetGene Email netgene@cbs.dtu.dk6.5' “Kozak ” Gelfand, M. S. (1995). Prediction of function in DNA sequence analyis. J. Comput. Biol. 2, 87-115.7.PolyA8.GENSCAN Web Email GENSCANGENSCAN /GENSCAN.html9. tRNAtRNA tRNA tRNAscan-SE tRNA 99% tRNA WebtRNAscan-SE /eddy/tRNAscan-SE/4.2X NMR1.20 ExPASyAACompIdent ( ) pI Mw( ) “ (ALL)” SWISS-PROT Email SWISS-PROT ( )TrEMBLAACompSim SWISS-PROT ExPASy PROPSEARCH 144 “ ” SWISS-PROT PIR WebExPASy http://www.expasy.ch/tools/PROSEARCH http://www.embl-heidelberg.de/prs.html2.Compute pI/MW ExPASyPeptideMass ExPASy LysC ArgC AspN GluCTGREASE FASTA -SAPSExPASy http://www.expasy.ch/tools/FASTA ftp:///pub/fasta/SAPS http://www.isrec.isb-sib.ch/software/SAPS_form.html3.“ ” nnPredict “H”( ) “E”( ) “-”( ) 79%PredictProtein SWISS-PROT MaxHom profile profile PHD 72% SOPMA “ ” GOR Levin PHD SOPMAnnPredict /~nomi/nnpredict.htmlPredictProtein /predictprotein/PredictProtein /predictprotein/SOPMA http://pbil.ibcp.fr/4.(Coiled Coils)COILSTMpred SWISS-PROT TmbaseSignalPCOILS /software/COILS_form.htmlTMpred /software/TMPRED_form.htmlSignalP http://www.cbs.dtu.dk/services/SignalP/5.“ ” “Threading” “ ” “Threading” PSI-BLASTSWISS-MODEL (First Approach mode) (Optimise mode) ExPdbCPHmodelsSWISS-MODEL http://www.expasy.ch/swissmod/SWISS-MODEL.htmlCPHmodels http://www.cbs.dtu.dk/services/CPHmodels/5.160 “ ” 60 “ ” “ ”Zucherkandl “ ”RNase C 0-30% 60 3000 -- 3000 4-5% DNA 8% 0.8% 1.1% 6 DNA. 60 --“ ” DNA 0.5 / /Motoo Kimura (1) (2)100% “ ” - “ ” random driftZuckerkandl Pauling“ ” “ ” “ ”C-5.2(evolutionary tree) (phylogenetic tree)PAM2501/ indelCLUSTALW 1 2 3 4 523maximum parsimony, MP maximum likelihood ML“A” “C” “A” “A”4BB 20 BB BB BB“ ” “ ” “ ” TBR tree bisection-reconnectionWagner Lake Hadamard Quartet puzzling ML565.3X ray NMR 70 [1]C “ ”12C3 CC30% 1.5 1/32“ ” PAM250 1 2 3 4PhylipPHYLIP 30 PHYLIP Mac, DOS, Unix, V AX/VMS, PHYLIP PAUPPAUP PAUP 3.0 MP PAUP 4.0 MLPAUP PHYLIP FastDNAml, MACCLADE, MEGA plus METREE, MOLPHY PAMLPHYLOGENETIC RESOURCES/subway/phylogen.htmlPHYLOGENY PROGRAMS/phylip/software.htmlPHYLOGENETIC ANALYSIS COMPUTER PROGRAMS/tree/programs/programs.htmlBIOCA TALOG MOLECULAR EVOLUTION :/biocat/phylogeny.htmlPHYLIP /phylip.htmlDNAEST (dbEST) SNPs1998 10 3 7 EST (Expressed Sequence Tags) 1999 12 200 90 1998 EST SNPs EST SNPs956.11. Wisconsin GCGGenetics Computer Group Wisconsin SeqLab GUI Wisconsin SeqLabWisconsin 120 Wisconsin GCG (GenBank , EMBL ) (PIR,SWISS-PROT, SP-TrEMBL) GCG Wisconsin BLAST BLAST LookUpGCG Wisconsin GCG Wisconsin GCG WisconsinSeqLab SeqLab(1) mRNA RNAmRNA ORFSeqLab Editor Functions Map Map Map 6 ORF ORF SeqLab Editor Edit Translate SeqLab EditorGap BestFit Gap BestFit(2)Functions LookUp LookUp Definiton, Author, Keyword Organism “and” & “or” | “but not” SWISS-PROT Description “lactate & dehydrogenase & h & chain”H lactate dehydrogenase H chain Output Manager SeqLab EditorFunctions PileUp PileUp Output Manager SeqLab Editor Features table(3)SeqLab Editor Functions FASTA FASTA Output Manager SeqLab Editor SeqLab Editor SeqLab EditorFunctions PileUp Output Manager SeqLab EditorFunctions PaupSearch PAUP Phylogenetic Analysis Using Parsimony GCG PaupDisplay PAUP GCG(4)contig Fragment Assmbly System GelStart GelEnter GelMerge contig GelAssemble Functions contig SeqLab EditorMap Frames TestCode Codon Preference Functions Edit Select Range EditFunctions BLAST BLAST Output Manager SeqLab Editor Main List(5)Functions PileUp PileUp Output Manager SeqLab Editor PileUp PileUp Options "realign a portion of an existing alignment "Edit Consensus Functions FindPatternsFindPatternsMotif Motif PROSITE PROSITE Motif 4.9 Motif(6) ProfileProfile profile ProfileProfileMake profile ProfileSearch profile ProfileSegment ProfileGap profile ProfileMake, ProfileSearch, ProfileSegments ProfileGap FunctionsGCG 2. ACEDBACEDB , Unix Macintosh OS Windows DNA , ACEDB ACEDB36.21restriction map kb cytogenetic map 10 4 kb STS STS content map radiation hybrid map 1Mb PCR STS STS TACs BACs STS 100% STS STS STS STS 1Mb Y AC bp STS STS STS DNA STS CEPH centre d Etudes du Polymorphisme Humain Y AC 10× ~1MbDNA gamma DNASTS DNA STS PCR STS PCR STS retention pattern STSSTS STS 1MSTS STS CEPH Y AC fingerprinting Alu inter-Alu product hybridization STS Y AC bin? FISH DNASTS ESTY AC STS DNA BAC 19 Lawrence Livemore2.NCBI GDB 1 NCBI EntrezEntrez NCBI Entrez DNA EntrezEntrez C. elegans2 GDBGDB GDB GDB NCBI GDB NCBI GDB WWW GDB3Entrez GDB Entrez GDB Entrez GDBGenethon 5264 1.6cM PostScript Genethon FTP GDBCooperative Human Linkage Center CHLC 10775 3.7cM1996 10 Horno sapiens Science 15000 Genethon STS 1000 1/5 UniGeneset NCBI ESTsGenethon 2cM the Whitehead Institute Stanford UniversityNCBI“ ” NCBI ScienceNCBI Mapview GDB What s New EntrezWhite head InstituteThe Whitehead Intitute/MIT Center for Genome Research STS Y AC 10000 12000 Whitehead G4 Genebridge 4 radiation hybrid panel 1Mbp Y AC 200kbp Genethon 150kb 20000 STSs WhiteheadWI Whitehead Institute Whitehead Center for Genome Research “ ” Human Physical Mapping Project pop-up STS Entrez STS GIF Macintosh PICT Whitehead GenBank STS Whitehead NCBIWhitehead STS3STS STS/Y ACSTSWhitehead STS/YAC STSs 2 STS 10Mb 1Mb STS/Y AC 1Mb STS 100 300kb 1Mb STS/Y ACSTS STS Y AC Y AC STS 5 Y AC STS 12.8 Y AC STS 2 Y AC STS 1 Y AC STSWhitehead Whitehead STS STS WhiteheadSTS WhiteheadSTS DNA PCR WWW TCP/IPWhitehead Genome Center WWW Primer PickingPCR WI Pick Primers DNA BLAST FASTA STS Whitehead STS/TACWhitehead STS/Y AC STSSTS CEPT mega-YAC STS/YAC 30000 1200 row plate column pool Y AC CEPH Y AC Research Genetics Corporation Whitehead Y AC 709 972 STSWhitehead Human Physical Mapping Project “Search for a Y AC to its address” pop-up Y AC Y AC Y AC Y AC Y AC “plate_row_column” “_” 709_A_1 Y AC carriage Y AC 709_a_1 709a1Y AC Search Y AC STS STSCEPH 40 50 Y AC Y AC STS FISHY AC Y AC STS STS STS STS STS STS Y ACWhiteheadSTS Whitehead STS/Y AC STS 93 PCR 1000 Whitehead Genebridge 4 radiation hybrid panel CEPH Y AC DNA PCR Whitehead PCR“rhv”sts_name1 001001011000001000000011010001101110011100101001211001110101010100101000sts_name2 000001111000001000000011010000001110011100101001211001110101010100100000PCR 0 PCR 1 2 “ ” “ ” G4rhp Whitehead “How the radiation hybrid maps were constructed” “G40” Research Genetics DNA Tab STSWhitehead “Place your own STSs on the genome framework map” STSEmail PCR EmailWhitehead STS Mac PICT Macintosh GIF Windows Uinx“ ” EmailRH Email98 Whitehead Whitehead Macintosh GIF Whitehead STSpop-up STSStanford UniversityStanford Human Genome Center G3 G4 G3 Stanford 375kb 8000 STS 3700 NCBI Stanford “ ”NCBIStanford Whitehead Research Genetics G3 STS STS Stanford Email G3 Stanford 75 STS 90PCR STS 83G3 DNA Stanford RH Protocol PCRStanford STS STS centiray cR STS Stanford STSStanford RH RH Server Web Submission Email Email STS Chromosome NumberEmail Stanford STS STS centirays STS Stanford STSCEPH Y AC1993 CEPH Centre d études du Polymorphisme Humain Genethon Y AC Y AC Y AC Y AC fingerprinting inter-Alu PCR FISH STS Y AC STS CEPH Y ACY AC inter-Alu PCR Y AC CEPH “level”1 level STS Y AC STS STS Y AC/Y AC2 STS Y AC inter-Alu PCR Y AC 2 Y AC/Y AC3 24 3 CEPH 4 CEPH 90 3CEPH Y ACCEPH Y AC QuickMap CEPH QuickMap QuickMap Sun CEPH QuickMap Infoclone STS Y AC Y AC inter-Alu PCRCEPH ECPH Genethon I Y AC STS Y AC plate_row_column _ _ 923_f_6 STS GDB D AFM20ZE3 AFM220ZE3 STS Y ACQuery CEPH STS STS Y AC Y AC PAC STS Alu-PCR probe Y AC inter-Alu PCR STS Y AC STS inter-Alu PCRY AC Query Y AC FISH STS inter-Alu PCRY AC PCR c CEPH E Y AC CEPH Y AC/Y AC a A PCR fCEPH Y AC Y AC Y AC DNA Y ACGDB NHGRI 3Whitehead Institute/MIT Center for Genome Research murine STS/Y AC 24000 Y AC 10000 STSMIT Whitehead Mouse Genetic and Physical Mapping Project STS WhiteheadWhitehead 6331 Copeland/Jenkins RFLP 1.1cM European Collaborative Interspecific Mouse BackCros 0.3cM ECJMBC 1997 5 5The Mouse Genome Database MGD Bar Harbor Jackson Laboratory MGD synteny MGD Jackson Laboratory Mouse Genome Informatics Mouse Genome DatabaseCEPH Y AC http://www.cephb.fr/ceph-genethon-map.htmlCHLC ECIMBC /MBx/MbxHomepage.htmlEntrez /Entrez/Entrez /Entrez/nentrez.overview.htmlGDB /GDB /gdb/hgp_resources.htmlGenethon FTP ftp://ftp.genethon.fr/pub/Gmap/Nature-1995I.M.A.G.E. Consortium /bbrp/image/iresources.htmlJackson /NHGRI /Data/Science /Science96/Stanford /Stanford RH /Mapping/rh/procedure/Whitehead /Whitehead FTP ftp:///pub/human_STS_releasesC.elegans ACEDB :8300/other/E.coli University of Wisonsin /D.melanogaster FlyBase :82/S.cerevisiae SGD,Stanford /Saccharomyces11.6.311.6.4 SNPDNA SNPs 1000 1 1000 SNPsSNPs SNPs SNPs SNPs 3000 SNP 100,000 SNPs SNP DNA MALDI-TOFSNPs SNP DNA7.1DNAcDNA cDNA (proteome) DNANPcDNA1cDNABrown /pbrown NHGRI Yidong Chen deArray,NHGRI cDNA ArrayDBArrayDBArrayDB cDNA ArrayDB cDNA ArrayDB ArrayDB GenBank IMAGE ArrayDB cDNA “ ”ArrayDB Unigene ()ArrayDB Web ArrayDB ID dbEST GenBank Unigene KEGGArrayDB 10K/15K BLASTNArrayDB ArrayViewer MultiExperiment viewerDeArray ArrayDB /DIR/LCG/15K/HTML212345mRNA data-normalizationDNA DNA12 “ ” DNA cDNA IMAGE clone_id3 Saccharomyces cerevisiae,Homo sapiens “ ”4 mRNA “ ”5Whitehead Affymetrix, Incyte,GeneLogic Affymetrix3 GeneX NCBI Gene Expression Omnibus; EBI ArrayExpress.XML /microarray/ EBI ArrayExpress , /arrayexpress3clustering analysis - support vector machines,SVMs“ ” cluster 1 2 hierarchical clustering 3 multidimensional scaling analysis,MDS Euclidean “ ”4 K-means “ ”well-separatedMichael Eisen Windows CLUSTER TREEVIEW pairwise average-linkage TREEVIEW CLUSTERCLUSTER /Eluclidean self organizing maps,SOMs - binary deterministic-annealing algorithm ,k-means Tamayo Windows SOMsCLUSTER TREEVIE - support vector machines,SVMs “ ” unsupervised clustering self-organizing mapshierarchical K-means “ ” cluster k-means “ ” “ ” cluster “ ” “ ” “ ”“ ” “ ” SVMs “ ” SVMs SVMs SOMs “ ” “ ” SVMsTREEVIEW7.2Marcotte Enright domain fusions two-hybrid system (mass spectrometry,MS) 2D PAGE DNA DNA microarray hybridization 5-50 30,000-300,000 30% 30% Marcotte Enright “ ” functionally linked .Marcotte phylogenetic profiles (domain-fusion analysis) mRNA (correlated messenger RNA expression patterns) Enrightfunctionally linkedcomponent proteins (fusion proteins) interface gene proximityMarcotte mRNA 97 DNA“ ” “ ” 50% 3-8 - Marcotte MSH6 DNA PMS1 RNAMarcotte 2,557 30% 15%Enright 215 mRNAstructural genomics 10,000A Adenineactive sitealignment alignment ofalignmentsallelesalpha carbon R-alternativesplicinghnRNA mRNAamino terminus(N-terminal)N 5'-anti-parallel DNA 5' 3'3' 5'base pair 1 DNA A TG C 2 DNAbeta turnsUBioinformaticsBiocomputingBasic Local Alignment Search Tool ( Blast)Blastblotting and hybridizationbootstrap testbranch and boundmethodbranchesC ( Cytosine)CAAT box CAAT C-A-A-T 80CAATcarboxy terminus ( —COOH) 3'-cDNAComplementaryDNA cDNA (DNA)RNA DNAcDNA library cDNA mRNA DNA DNAcentral dogma DNA ?RNA ? proteincharacter charged amino acid pHchromatin DNAchromosome DNA DNAclonecloning DNACoding sequence DNA CodonComplementary 1 G C; A T; A U2ComputationalMolecular Biologyconformationconsensus sequenceconserved sequenceContigconvergent evolutioncore foldCpG island CpG 500bp 3000bp CpGcrystal degeneracydenatured proteindeoxyribonucleic acid (DNA)DNADNAdipeptidedisulfide bond DNA DNAdomaindot plotdynamic programmingORNL Grail Form (v1.3)/Grail-1.3/2006-5-9 20:11:14。