Identifying context-specific transcription factor targets from prior knowledge and gene expression data

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

Abstract

Numerous methodologies, assays, and databases presently provide candidate targets of transcription factors (TFs). However, TFs rarely regulate their targets universally. The context of activation of a TF can change the transcriptional response of targets. Direct multiple regulation typical to mammalian genes complicates direct inference of TF targets from gene expression data. We present a novel statistic that infers context-specific TF regulation based upon the CoGAPS algorithm, which infers overlapping gene expression patterns resulting from coregulation. Numerical experiments with simulated data showed that this statistic correctly inferred targets that are common to multiple TFs, except in cases where the signal from a TF is negligible relative to noise level and signal from other TFs. The statistic is robust to moderate levels of error in the simulated gene sets, identifying fewer false positives than false negatives. Significantly, the regulatory statistic refines the number of transcription factor targets relevant to cell signaling in gastrointestinal stromal tumors (GIST) to genes consistent with the phosphorylation patterns of TFs identified in previous studies. As formulated, the proposed regulatory statistic has wide applicability to inferring set membership in integrated datasets. This statistic could be naturally extended to account for prior probabilities of set membership or to add candidate gene targets.

Original languageEnglish (US)
Title of host publicationProceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2012
Pages125-130
Number of pages6
DOIs
StatePublished - Dec 1 2012
Event2012 IEEE International Conference on Bioinformatics and Biomedicine, BIBM2012 - Philadelphia, PA, United States
Duration: Oct 4 2012Oct 7 2012

Publication series

NameProceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2012

Other

Other2012 IEEE International Conference on Bioinformatics and Biomedicine, BIBM2012
CountryUnited States
CityPhiladelphia, PA
Period10/4/1210/7/12

Keywords

  • Bioinformatics
  • Genetic expression
  • Genomics

ASJC Scopus subject areas

  • Biomedical Engineering
  • Health Informatics

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