Unsupervised pattern discovery in human chromatin structure through genomic segmentation

Sequence census methods like ChIP-seq now produce an unprecedented amount of genome-anchored data. We have developed an integrative method to identify patterns from multiple experiments simultaneously while taking full advantage of high-resolution data, discovering joint patterns across different assay types. We apply this method to ENCODE chromatin data for the human chronic myeloid leukemia cell line K562, including ChIP-seq data on covalent histone modifications and transcription factor binding, and DNase-seq and FAIRE-seq readouts of open chromatin. In an unsupervised fashion, we identify patterns associated with transcription start sites, gene ends, enhancers, CTCF elements, and repressed regions. The method yields a model which elucidates the relationship between assay observations and functional elements in the genome. This model identifies sequences likely to affect transcription, and we verify these predictions in laboratory experiments. We have made software and an integrative genome browser track freely available (noble.gs.washington.edu/proj/segway/).