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Modeling Transcription Factor Target Promoters 141Table 2 (Continued)Gene- Human sequenceType ID (−220 to +220 of ERE) Mouse orthologous sequenceMe 119 chr2:70907791-70908244(−) chr6:86456544-86456996(+)Me 2313 chr11:128068485-128068938(+) chr9:32463271-32463723(−)Me 4035 chr12:55809318-55809771(+) chr10:127356571-127357023(−)Me 5048 chr17:2444402-2444855(+) chr11:74448879-74449331(−)Me 5101 chr13:66702595-66703048(−) chr14:88356851-88357303(−)Me 5783 chr4:87872450-87872903(+) chr5:102458949-102459401(+)Me 7702 chr11:9438737-9439190(+) chr7:103914186-103914638(+)Me 7745 chr6:28213421-28213874(+) chr13:21014835-21015287(−)Me 8667 chr8:117846957-117847410(−) chr15:51873755-51874207(−)Me 9774 chr6:136651331-136651784(−) chr10:20240553-20241005(+)Me 11096 chr21:27259775-27260228(−) chr16:84999666-85000118(−)Me 53335 chr2:60689565-60690018(−) chr11:23975167-23975619(+)Me 55064 chr9:4656506-4656959(−) chr19:28220480-28220932(−)Me 79661 chr15:73426510-73426963(+) chr9:57261658-57262110(−)Me 80207 chr19:50779773-50780226(−) chr7:16096867-16097319(+)Me 80309 chr2:228872394-228872847(−) chr1:83738473-83738925(−)Me 85015 chr6:100069931-100070384(−) chr4:21845309-21845761(+)Me 116092 chr20:43853917-43854370(+) chr2:164202655-164203107(+)Me 140775 chr17:18159358-18159811(+) chr11:60503208-60503660(+)Me 283078 chr10:28074133-28074586(−) chr18:7046824-7047276(+)Me 200558 chr2:68606356-68606809(+) chr6:88107914-88108471(+)Me 92014 chr9:37894330-37894344(−) chr4:45324576-45325138(+)Me 7072 chr2:70387601-70387615(−) chr6:86876812-86877270(+)Obtained from Cheng et al. (3). The locations of the human sequence around the consensus EREand the mouse orthologous region are given in columns 3 and 4. The genomic coordinates areaccording to the human (May 2004 Build—hg17) and the mouse (March 2005—mm6) assemblies.cross-validation was 86% for acetylated targets and 84% for methylated targets.Based on the splitting rules at each node and applying the “if then” rules in theCART tree, three cis-regulatory modules i.e., ERE + MYC, ERE + MYB, andERE + E47 + CETS168, were identified for upregulated (i.e., more acetylated)targets and four modules (ERE + HNF3α, ERE + AP3, ERE + E2A, and ERE +E47) were identified for downregulated (i.e., more methylated) targets (Fig. 3B).Overall, CART and Random Forest analyses identified seven distinct cis-regulatorymodules for up- or downregulated ER-α target genes. The user should trydifferent top ranking variables (TFs) to construct various CART trees and shouldfocus on those modules that are predicted consistently.4. Notes1. Despite great progress, TFBS prediction by computational approaches alone is stillfar from perfect. The existing programs that combine PWM and comparative

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