Methods for ChIP-seq analysis: A practical workflow and advanced applications

Methods. 2021 Mar:187:44-53. doi: 10.1016/j.ymeth.2020.03.005. Epub 2020 Mar 30.


Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a central method in epigenomic research. Genome-wide analysis of histone modifications, such as enhancer analysis and genome-wide chromatin state annotation, enables systematic analysis of how the epigenomic landscape contributes to cell identity, development, lineage specification, and disease. In this review, we first present a typical ChIP-seq analysis workflow, from quality assessment to chromatin-state annotation. We focus on practical, rather than theoretical, approaches for biological studies. Next, we outline various advanced ChIP-seq applications and introduce several state-of-the-art methods, including prediction of gene expression level and chromatin loops from epigenome data and data imputation. Finally, we discuss recently developed single-cell ChIP-seq analysis methodologies that elucidate the cellular diversity within complex tissues and cancers.

Keywords: ChIP-seq; Chromatin state; Histone modifications; Machine learning; Quality assessment; Single-cell analysis.

Publication types

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

MeSH terms

  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromatin Immunoprecipitation Sequencing / methods*
  • Epigenomics / methods*
  • Histone Code / genetics
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Single-Cell Analysis / methods
  • Workflow


  • Chromatin
  • Histones