RT Journal
A1 Thompson, William
A1 Palumbo, Michael J.
A1 Wasserman, Wyeth W.
A1 Liu, Jun S.
A1 Lawrence, Charles E.
T1 Decoding Human Regulatory Circuits
JF Genome Research 
JO Genome Research 
YR 2004 
FD October 01 
VO 14 
IS 10a 
SP 1967 
OP 1974 
DO 10.1101/gr.2589004 
UL http://genome.cshlp.org/content/14/10a/1967.abstract 
AB 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.