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oai:recercat.cat:10230/528412025-12-12T02:02:20Zcom_2072_6col_2072_452952

Identification of chromatin loops from Hi-C interaction matrices by CTCF-CTCF topology classification Galan Martínez, Silvia, 1992- Serra, François Marti-Renom, Marc A. Genòmica Cromatina Epigenètica 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. Funding: European Research Council under the 7th Framework Program FP7/2007–2013 [ERC grant agreement 609989]; European Union's Horizon 2020 research and innovation programme [676556]; Spanish Ministerio de Ciencia e Innovación [BFU2017-85926-P, PID2020-115696RB-I00]; CRG acknowledges support from ‘Centro de Excelencia Severo Ochoa 2013–2017’, SEV-2012-0208 and the CERCA Programme/Generalitat de Catalunya as well as support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III and the EMBL partnership; Generalitat de Catalunya through Departament de Salut and Departament d’Empresa i Coneixement; European Regional Development Fund (ERDF) by the Spanish Ministry of Science and Innovation corresponding to the Programa Opertaivo FEDER Plurirregional de España (POPE) 2014–2020; Secretaria d’Universitats i Recerca, Departament d’Empresa i Coneixement of the Generalitat de Catalunya corresponding to the programa Operatiu FEDER Catalunya 2014–2020. Funding for open access charge: Spanish Ministerio de Ciencia, Innovación y Universidades [BFU2017-85926-P] 2022-04-07T06:10:29Z 2022-04-07T06:10:29Z 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 2631-9268 http://hdl.handle.net/10230/52841 http://dx.doi.org/10.1093/nargab/lqac021 eng info:eu-repo/grantAgreement/EC/H2020/676556 info:eu-repo/grantAgreement/EC/FP7/609989 info:eu-repo/grantAgreement/ES/2PE/BFU2017-85926-P © Silvia Galan, François Serra, Marc A. Marti-Renom 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Oxford University Press