TY - JOUR A1 - Thompson, William A1 - Palumbo, Michael J. A1 - Wasserman, Wyeth W. A1 - Liu, Jun S. A1 - Lawrence, Charles E. T1 - Decoding Human Regulatory Circuits Y1 - 2004/10/01 JF - Genome Research JO - Genome Research SP - 1967 EP - 1974 DO - 10.1101/gr.2589004 VL - 14 IS - 10a UR - http://genome.cshlp.org/content/14/10a/1967.abstract N2 - 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. ER -