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

IEEE Trans Nanobioscience. 2013 Sep;12(3):142-9. doi: 10.1109/TNB.2013.2263390. Epub 2013 May 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cell Line, Tumor
  • Computer Simulation
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / metabolism
  • Gene Expression Profiling / methods*
  • Genomics / methods*
  • Humans
  • Models, Genetic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Neoplasm Proteins
  • Transcription Factors