Spatial clustering for identification of ChIP-enriched regions (SICER) to map regions of histone methylation patterns in embryonic stem cells.

Chromatin states are the key to embryonic stem cell pluripotency and differentiation. Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-Seq) is increasingly used to map chromatin states and to functionally annotate the genome. Many ChIP-Seq profiles, especially those of histone methylations, are noisy and diffuse. Here we describe SICER (Zang et al., Bioinformatics 25(15):1952-1958, 2009), an algorithm specifically designed to identify disperse ChIP-enriched regions with high sensitivity and specificity. This algorithm has found a lot of applications in epigenomic studies. In this Chapter, we will demonstrate in detail how to run SICER to delineate ChIP-enriched regions and assess their statistical significance, and to identify regions of differential enrichment when two chromatin states are compared.