Decoding human regulatory circuits.
Clusters of transcription factor binding sites (TFBSs) which direct gene expression constitute cis-regulatory modules (CRMs). We present a novel algorithm, based on Gibbs sampling, which locates, de novo, the cis features of these CRMs, their component TFBSs, and the properties of their spatial distribution. The algorithm finds 69% of experimentally reported TFBSs and 85% of the CRMs in a reference data set of regions upstream of genes differentially expressed in skeletal muscle cells. A discriminant procedure based on the output of the model specifically discriminated regulatory sequences in muscle-specific genes in an independent test set. Application of the method to the analysis of 2710 10-kb fragments upstream of annotated human genes identified 17 novel candidate modules with a false discovery rate </=0.05, demonstrating the applicability of the method to genome-scale data.
Thompson
William
W
Center for Bioinformatics, Wadsworth Center, New York State Department of Health, Albany, New York 12208, USA. thompson@wadsworth.org
Palumbo
Michael J
MJ
Wasserman
Wyeth W
WW
Liu
Jun S
JS
Lawrence
Charles E
CE
D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D006801:Humans; D008957:Models, Genetic; D018482:Muscle, Skeletal / Q000502:physiology; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors