Combinatorial Identification of Broad Association Regions with ChIP-seq Data.

Motivation: Differentiation of cells into different cell types involves many types of chromatin modifications, and mapping these modifications is a key computational task as researchers uncover different aspects of that process. Modifications associated with heterochromatin formation pose new challenges in this context because we must define very broad regions that have only a moderately stronger signal than the rest of the chromatin. Lamin-associated domains (LADs) are a prime example of such regions. Results: We present Combinatorial Identification of Broad Association Regions (CIBAR), a new method to identify these types of broad regions. CIBAR is based on an efficient solution to a natural combinatorial problem, which adapts to widely variable yields of reads from ChIP-seq data and the associated controls and performs competitively with previous methods, including DamID, which has been used in many publications on LADs but cannot be applied in most in vivo situations.