Decoding human regulatory circuits.

William Thompson; Michael J Palumbo; Wyeth W Wasserman; Jun S Liu; Charles E Lawrence

doi:10.1101/gr.2589004

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Decoding human regulatory circuits.

William Thompson·Michael J Palumbo·Wyeth W Wasserman·Jun S Liu·Charles E Lawrence

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Abstract

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.

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Algorithms Animals Binding Sites Biological Evolution Humans Models, Genetic Muscle, Skeletal Protein Binding Transcription Factors Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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William Thompson, Michael J Palumbo, Wyeth W Wasserman, Jun S Liu, Charles E Lawrence. 2004. Decoding human regulatory circuits.. https://doi.org/10.1101/gr.2589004

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