Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification

Galan Martínez, Silvia, 1992-; Serra, François; Marti-Renom, Marc A.

doi:http://dx.doi.org/10.1093/nargab/lqac021

Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification

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Galan S, Serra F, Marti-Renom MA. Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification. NAR Genom Bioinform. 2022 Mar 8;4(1):lqac021. DOI: 10.1093/nargab/lqac021

Abstract

Genome-wide profiling of long-range interactions has revealed that the CCCTC-Binding factor (CTCF) often anchors chromatin loops and is enriched at boundaries of the so-called Topologically Associating Domains, which suggests that CTCF is essential in the 3D organization of chromatin. However, the systematic topological classification of pairwise CTCF-CTCF interactions has not been yet explored. Here, we developed a computational pipeline able to classify all CTCF-CTCF pairs according to their chromatin interactions from Hi-C experiments. The interaction profiles of all CTCF-CTCF pairs were further structurally clustered using self-organizing feature maps and their functionality characterized by their epigenetic states. The resulting clusters were then input to a convolutional neural network aiming at the de novo detecting chromatin loops from Hi-C interaction matrices. Our new method, called LOOPbit, is able to automatically detect significant interactions with a higher proportion of enhancer-promoter loops compared to other callers. Our highly specific loop caller adds a new layer of detail to the link between chromatin structure and function.