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

Research output: Contribution to journalArticle

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 TF 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)
Article number6516960
Pages (from-to)142-149
Number of pages8
JournalIEEE Transactions on Nanobioscience
Volume12
Issue number3
DOIs
StatePublished - 2013

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Transcription factors
Gene expression
Transcription Factors
Gene Expression
Statistics
Genes
Overlapping Genes
Cell signaling
Phosphorylation
Gastrointestinal Stromal Tumors
Noise
Tumors
Assays
Chemical activation
Databases

Keywords

  • Bioinformatics
  • genetic expression
  • genomics

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Medicine (miscellaneous)
  • Bioengineering
  • Computer Science Applications
  • Biotechnology
  • Biomedical Engineering
  • Electrical and Electronic Engineering
  • Medicine(all)

Cite this

Identifying context-specific transcription factor targets from prior knowledge and gene expression data. / Fertig, Elana; Favorov, Alexander; Ochs, Michael F.

In: IEEE Transactions on Nanobioscience, Vol. 12, No. 3, 6516960, 2013, p. 142-149.

Research output: Contribution to journalArticle

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