CIS: Compound importance sampling method for protein-DNA binding site p-value estimation

Y. Barash, G. Elidan, T. Kaplan, N. Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Motivation: A key aspect of transcriptional regulation is the binding of transcription factors to sequence-specific binding sites that allow them to modulate the expression of nearby genes. Given models of such binding sites, one can scan regulatory regions for putative binding sites and construct a genome-wide regulatory network. In such genome-wide scans, it is crucial to control the amount of false positive predictions. Recently, several works demonstrated the benefits of modeling dependencies between positions within the binding site. Yet, computing the statistical significance of putative binding sites in this scenario remains a challenge. Results: We present a general, accurate and efficient method for computing p-values of putative binding sites that is applicable to a large class of probabilistic binding site and background models. We demonstrate the accuracy of the method on synthetic and real-life data.

Original languageEnglish
Pages (from-to)596-600
Number of pages5
JournalBioinformatics
Volume21
Issue number5
DOIs
StatePublished - 1 Mar 2005

Bibliographical note

Funding Information:
We thank Noa Shefi and the anonymous reviewers for useful comments on an earlier version of this manuscript. This work was supported in part by the Israel Science Foundation (ISF), and the Israeli Ministry of Science. Y. Barash was supported by an Eshkol fellowship. G. Elidan and T. Kaplan were supported by Horowitz fellowships. N. Friedman was supported by an Alon fellowship and the Harry & Abe Sherman Senior Lectureship in Computer Science.

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