Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.03.06.531254v1?rss=1
Authors: Smirnov, D., Toiber, D., Gelfand, M., Khrameeva, E.
Abstract:
Motivation: In many eukaryotes, chromosomes are organized as strings of spatially segregated Topologically Associating Domains (TADs), characterized by a substantially increased frequency of interactions within them. Boundaries of TADs are highly enriched in histone acetylation chromatin marks and occupied binding sites of architectural proteins, highlighting the functional role of TADs in the regulation of gene expression. While many computational approaches for the identification of TADs have been developed, it remains challenging because of their nested structure, resulting in weakly overlapping sets of TADs at different scales. Results: Here, we propose a novel algorithm optimalTAD for identifying the optimal set of TADs based on epigenetic marks enrichment. Assuming that the most dramatic enrichment corresponds to the best annotation of TAD boundaries, our algorithm optimizes TAD calling parameters by maximizing the difference in chromatin mark levels between TADs and their boundaries. Using this algorithm, we annotated TADs in several publicly available Hi-C datasets and identified a set of epigenetic marks that are best suited for TAD prediction.
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