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Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale

To learn how genomic sequence influences multiscale three-dimensional (3D) genome architecture, this manuscript presents a sequence-based deep learning approach, Orca, that predicts directly from sequence the 3D genome architecture from kilobase to whole-chromosome scale. Orca captures the sequence...

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Detalles Bibliográficos
Autor principal: Zhou, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186125/
https://www.ncbi.nlm.nih.gov/pubmed/35551308
http://dx.doi.org/10.1038/s41588-022-01065-4
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author Zhou, Jian
author_facet Zhou, Jian
author_sort Zhou, Jian
collection PubMed
description To learn how genomic sequence influences multiscale three-dimensional (3D) genome architecture, this manuscript presents a sequence-based deep learning approach, Orca, that predicts directly from sequence the 3D genome architecture from kilobase to whole-chromosome scale. Orca captures the sequence dependencies of structures including chromatin compartments and topologically associating domains, as well as diverse types of interactions from CTCF-mediated to enhancer-promoter interactions and Polycomb-mediated interactions with cell-type specificity. Orca enables various applications including predicting structural variant effects on multiscale genome organization and it recapitulated effects of experimentally studied variants at varying sizes (300bp–90Mb). Moreover, Orca enables in silico virtual screens to probe the sequence-basis of 3D genome organization at different scales. At the submegabase scale, it predicted specific transcription factor motifs underlying cell-type-specific genome interactions. At the compartment scale, virtual screens of sequence activities suggest a new model for the sequence basis of chromatin compartments with a prominent role of transcription start sites.
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spelling pubmed-91861252022-11-15 Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale Zhou, Jian Nat Genet Article To learn how genomic sequence influences multiscale three-dimensional (3D) genome architecture, this manuscript presents a sequence-based deep learning approach, Orca, that predicts directly from sequence the 3D genome architecture from kilobase to whole-chromosome scale. Orca captures the sequence dependencies of structures including chromatin compartments and topologically associating domains, as well as diverse types of interactions from CTCF-mediated to enhancer-promoter interactions and Polycomb-mediated interactions with cell-type specificity. Orca enables various applications including predicting structural variant effects on multiscale genome organization and it recapitulated effects of experimentally studied variants at varying sizes (300bp–90Mb). Moreover, Orca enables in silico virtual screens to probe the sequence-basis of 3D genome organization at different scales. At the submegabase scale, it predicted specific transcription factor motifs underlying cell-type-specific genome interactions. At the compartment scale, virtual screens of sequence activities suggest a new model for the sequence basis of chromatin compartments with a prominent role of transcription start sites. 2022-05 2022-05-12 /pmc/articles/PMC9186125/ /pubmed/35551308 http://dx.doi.org/10.1038/s41588-022-01065-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Zhou, Jian
Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title_full Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title_fullStr Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title_full_unstemmed Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title_short Sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
title_sort sequence-based modeling of three-dimensional genome architecture from kilobase to chromosome scale
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186125/
https://www.ncbi.nlm.nih.gov/pubmed/35551308
http://dx.doi.org/10.1038/s41588-022-01065-4
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