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PMID: 15466295 Published · ppublish English 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.

Decoding human regulatory circuits.

Genome research ·Vol. 14 ·No. 10A ·2004-10-00 ·Pages 1967-74

Thompson W, Palumbo MJ, Wasserman WW, Liu JS, Lawrence CE

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.

MeSH Terms
Algorithms Animals Binding Sites Biological Evolution Humans Models, Genetic Muscle, Skeletal/physiology Protein Binding Transcription Factors/metabolism
Chemicals
Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Thompson William
Center for Bioinformatics, Wadsworth Center, New York State Department of Health, Albany, New York 12208, USA. [email protected]
Palumbo Michael J
Wasserman Wyeth W
Liu Jun S
Lawrence Charles E
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.2589004
Email
[email protected]
Published
2004-10-00
Pages
1967-74
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC524421
Subset
IM
Grants
Canadian Institutes of Health Research · 64231 · Canada
Canadian Institutes of Health Research · 69153 · Canada
NHGRI NIH HHS · R01 HG001257 · United States
NHGRI NIH HHS · R01HG01257 · United States
External Links
PubMed source DOI: 10.1101/gr.2589004 PMC Full Text View journal details
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