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

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.