Thompson, WilliamPalumbo, Michael J.Wasserman, Wyeth W.Liu, JunLawrence, Charles E.2016-05-132004Thompson, W. 2004. “Decoding Human Regulatory Circuits.” Genome Research 14 (10a) (September 13): 1967–1974. doi:10.1101/gr.2589004.1088-9051http://nrs.harvard.edu/urn-3:HUL.InstRepos:27002631Clusters 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.en-USJournal Article2016-05-1310.1101/gr.2589004