An integrative method to decode regulatory logics in gene transcription

Nat Commun. 2017 Oct 19;8(1):1044. doi: 10.1038/s41467-017-01193-0.

Abstract

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF-TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Cell Differentiation
  • Computational Biology / methods
  • Computer Simulation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Gene Regulatory Networks*
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Kinetics
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Transcription Factors