Genome-wide discovery of modulators of transcriptional interactions in human B lymphocytes

Kai Wang, Ilya Nemenman, Nilanjana Banerjee, Adam A. Margolin, Andrea Califano

Research output: Chapter in Book/Report/Conference proceedingConference contribution

26 Scopus citations

Abstract

Transcriptional interactions in a cell are modulated by a variety of mechanisms that prevent their representation as pure pairwise interactions between a transcription factor and its target(s). These include, among others, transcription factor activation by phosphorylation and acetylation, formation of active complexes with one or more cofactors, and mRNA/protein degradation and stabilization processes. This paper presents a first step towards the systematic, genome-wide computational inference of genes that modulate the interactions of specific transcription factors at the post-transcriptional level. The method uses a statistical test based on changes in the mutual information between a transcription factor and each of its candidate targets, conditional on the expression of a third gene. The approach was first validated on a synthetic network model, and then tested in the context of a mammalian cellular system. By analyzing 254 microarray expression profiles of normal and tumor related human B lymphocytes, we investigated the post transcriptional modulators of the MYC proto-oncogene, an important transcription factor involved in tumorigenesis. Our method discovered a set of 100 putative modulator genes, responsible for modulating 205 regulatory relationships between MYC and its targets. The set is significantly enriched in molecules with function consistent with their activities as modulators of cellular interactions, recapitulates established MYC regulation pathways, and provides a notable repertoire of novel regulators of MYC function. The approach has broad applicability and can be used to discover modulators of any other transcription factor, provided that adequate expression profile data are available.

Original languageEnglish (US)
Title of host publicationResearch in Computational Molecular Biology - 10th Annual International Conference, RECOMB 2006, Proceedings
Pages348-362
Number of pages15
StatePublished - Jul 14 2006
Event10th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2006 - Venice, Italy
Duration: Apr 2 2006Apr 5 2006

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume3909 LNBI
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

Other10th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2006
CountryItaly
CityVenice
Period4/2/064/5/06

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ASJC Scopus subject areas

  • Theoretical Computer Science
  • Computer Science(all)

Cite this

Wang, K., Nemenman, I., Banerjee, N., Margolin, A. A., & Califano, A. (2006). Genome-wide discovery of modulators of transcriptional interactions in human B lymphocytes. In Research in Computational Molecular Biology - 10th Annual International Conference, RECOMB 2006, Proceedings (pp. 348-362). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 3909 LNBI).