Assessing computational methods for transcription factor target gene identification based on ChIP-seq data

PLoS Comput Biol. 2013;9(11):e1003342. doi: 10.1371/journal.pcbi.1003342. Epub 2013 Nov 21.

Abstract

Chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) has great potential for elucidating transcriptional networks, by measuring genome-wide binding of transcription factors (TFs) at high resolution. Despite the precision of these experiments, identification of genes directly regulated by a TF (target genes) is not trivial. Numerous target gene scoring methods have been used in the past. However, their suitability for the task and their performance remain unclear, because a thorough comparative assessment of these methods is still lacking. Here we present a systematic evaluation of computational methods for defining TF targets based on ChIP-seq data. We validated predictions based on 68 ChIP-seq studies using a wide range of genomic expression data and functional information. We demonstrate that peak-to-gene assignment is the most crucial step for correct target gene prediction and propose a parameter-free method performing most consistently across the evaluation tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Binding Sites*
  • Chromatin Immunoprecipitation / methods*
  • Databases, Genetic
  • Genome
  • Genomics / methods*
  • Mice
  • Models, Statistical
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics*

Substances

  • Transcription Factors

Grants and funding

This work was funded by the European Commission FP7 (EuroSyStem FP7-200720 www.eurosystemproject.eu, SyBoSS FP7-242129 www.syboss.eu), the Klaus Tschira Foundation (http://www.klaus-tschira-stiftung.de/) and a CRTD Seed Grant (Grant ID 043_261581 http://www.crt-dresden.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.