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Gene Expression Transcription Regulation,Dafna AradNoa Gordon20/5/02, Transcription Factors (TFs) Regulatory Motifs ., , , : cis / trans / on/off DNA , - RNA Pol ., , ? ? ? ?,Bucher P.:Regulatory elements and expression profilesCurr Opin Struct Biol 9 400-407, - . ., . , ., ,Bottom up ( ) ( )Top down . ( , ),Church GM: Computational Identification of Cis-regulatory Elements Associated with Groups of Functionally Related Genes in Saccharomyces cerevisiae J. Mol Biol 296 1205-1214, : AlignACE(Align nucleic Acid Conserved Elements) Gibbs Sampling algorithm,AlignACE, : . . . . .,AlignACE, , Regulon. : RNA - Clustering ,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,AlignACE Example,300-600 bp of upstream sequence per gene are searched in Saccharomyces cerevisiae.,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,AAAAGAGTCA,AAATGACTCA,AAGTGAGTCA,AAAAGAGTCA,GGATGAGTCA,AAATGAGTCA,GAATGAGTCA,AAAAGAGTCA,*, ,MAP score = 20.37 (maximum),HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,*,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,*,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,MAP score = -10.0,HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,*,sampling,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,Add?,*,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,TCTCTCTCCA,HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3, 2 -?alignments,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,*,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,Add?,*,TGAAAAATTC,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,Remove.,ATGAAAAAAT,HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3, 2 -?alignments,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,*,GACATCGAAA,GCACTTCGGC,GAGTCATTAC,GTAAATTGTC,CCACAGTCCG,TGTGAAGCAC,* *,GACATCGAAAC,GCACTTCGGCG,GAGTCATTACA,GTAAATTGTCA,CCACAGTCCGC,TGTGAAGCACA,HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3, 2 -?alignments,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAGAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATGACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTCACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAGAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTCATCCCGAACATGAAA,5- ATTGATTGACTCATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTCATTCTGACTCTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,AAAAGAGTCA,AAATGACTCA,AAGTGAGTCA,AAAAGAGTCA,GGATGAGTCA,AAATGAGTCA,GAATGAGTCA,AAAAGAGTCA,*, ,MAP score = 20.37 (maximum),HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3,5- TCTCTCTCCACGGCTAATTAGGTGATCATGAAAAAATGAAAAATTCATGAGAAAAXAGTCAGACATCGAAACATACAT,5- ATGGCAGAATCACTTTAAAACGTGGCCCCACCCGCTGCACCCTGTGCATTTTGTACGTTACTGCGAAATXACTCAACG,5- CACATCCAACGAATCACCTCACCGTTATCGTGACTXACTTTCTTTCGCATCGCCGAAGTGCCATAAAAAATATTTTTT,5- TGCGAACAAAAXAGTCATTACAACGAGGAAATAGAAGAAAATGAAAAATTTTCGACAAAATGTATAGTCATTTCTATC,5- ACAAAGGTACCTTCCTGGCCAATCTCACAGATTTAATATAGTAAATTGTCATGCATATGACTXATCCCGAACATGAAA,5- ATTGATTGACTXATTTTCCTCTGACTACTACCAGTTCAAAATGTTAGAGAAAAATAGAAAAGCAGAAAAAATAAATAA,5- GGCGCCACAGTCCGCGTTTGGTTATCCGGCTGACTXATTCTGACTXTTTTTTGGAAAGTGTGGCATGTGCTTCACACA,AAAAGAGTCA,AAATGACTCA,AAGTGAGTCA,AAAAGAGTCA,GGATGAGTCA,AAATGAGTCA,GAATGAGTCA,AAAAGAGTCA,*,masking,HIS7,ARO4,ILV6,THR4,ARO1,HOM2,PRO3, . . sampling .,MAP ScoreMaximum a priori log likelihood, .MAP Score = N log R :N - .R - , : -1000 , 10 -2000 5=R.,MAP Score, MAP Score :N ( ) . . ., AlignACE , :248 . 29 . false positive ORFs, AlignACE (), 3311 . :Group specificityPositional bias,Group Specificity Score, MAP Score , . A-rich motifs .Group Specificity Score (ScanACE ). , .,ScanACE, . AlignACE . , .,Positional Bias, ( ScanACE) . .,Clustering, CompareACE. clustering 6 . 1 - 1- -1 ., AlignACE (), AlignACE (), , - clustering 54 , -25 . AlignACE . . S12 RRPE - positional bias . rRMA., AlignACE (),
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