Principles of ChIP-seq Data Analysis Illustrated with Examples

Chromatin immunoprecipitation (ChIP) followed by highthroughput sequencing (ChIP-seq) is a powerful method to determine how transcription factors and other chromatin-associated proteins interact with DNA in order to regulate gene transcription. A single ChIPseq experiment produces large amounts of highly reproducible data. The challenge is to extract knowledge from the data by thoughtful application of appropriate bioinformatics tools. Here we present a concise introduction into ChIP-seq data analysis in the form of a tutorial based on tools developed by our group. We expose biological questions, explain methods and provide guidelines for the interpretation of the results. While this article focuses on ChIP-seq, most of the algorithms and tools we present are applicable to other chromatin profiling assays based on next generation sequencing (NGS) technology as well.