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PMID: 15653829 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Making connections between novel transcription factors and their DNA motifs.

Genome research ·Vol. 15 ·No. 2 ·2005-02-00 ·Pages 312-20

Tan K, McCue LA, Stormo GD

Abstract

The key components of a transcriptional regulatory network are the connections between trans-acting transcription factors and cis-acting DNA-binding sites. In spite of several decades of intense research, only a fraction of the estimated approximately 300 transcription factors in Escherichia coli have been linked to some of their binding sites in the genome. In this paper, we present a computational method to connect novel transcription factors and DNA motifs in E. coli. Our method uses three types of mutually independent information, two of which are gleaned by comparative analysis of multiple genomes and the third one derived from similarities of transcription-factor-DNA-binding-site interactions. The different types of information are combined to calculate the probability of a given transcription-factor-DNA-motif pair being a true pair. Tested on a study set of transcription factors and their DNA motifs, our method has a prediction accuracy of 59% for the top predictions and 85% for the top three predictions. When applied to 99 novel transcription factors and 70 novel DNA motifs, our method predicted 64 transcription-factor-DNA-motif pairs. Supporting evidence for some of the predicted pairs is presented. Functional annotations are made for 23 novel transcription factors based on the predicted transcription-factor-DNA-motif connections.

MeSH Terms
Algorithms Base Composition/genetics Binding Sites/genetics DNA, Bacterial/genetics Genome, Bacterial Gram-Negative Bacteria/cytology,genetics,metabolism Peptides/genetics Phylogeny Predictive Value of Tests Protein Binding/genetics Protein Structure, Tertiary/genetics Regulon/genetics Transcription Factors/genetics,metabolism Transcription, Genetic/genetics
Chemicals
DNA, Bacterial Peptides Transcription Factors
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tan Kai
Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
McCue Lee Ann
Stormo Gary D
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Article Info
Journal
Genome research
Abbr.
Genome Res
ISSN
1088-9051
DOI
10.1101/gr.3069205
Published
2005-02-00
Epub
2005-00-14
Pages
312-20
Language
English
Region
United States
NLM ID
9518021
PMCID
PMC546533
Subset
IM
Grants
NHGRI NIH HHS · R01 HG000249 · United States
NHGRI NIH HHS · HG 00249 · United States
External Links
PubMed source DOI: 10.1101/gr.3069205 PMC Full Text View journal details
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