Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts

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作者
Jonas Paulsen
Monika Sekelja
Anja R. Oldenburg
Alice Barateau
Nolwenn Briand
Erwan Delbarre
Akshay Shah
Anita L. Sørensen
Corinne Vigouroux
Brigitte Buendia
Philippe Collas
机构
[1] University of Oslo,Department of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine
[2] Université Paris 7-CNRS,Institut BFA
[3] INSERM,Norwegian Center for Stem Cell Research
[4] UMR S938,undefined
[5] Centre de Recherches Saint-Antoine,undefined
[6] UPMC Université Paris 6 UMR S938,undefined
[7] ICAN,undefined
[8] AP-HP Hôpital Tenon,undefined
[9] Oslo University Hospital,undefined
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关键词
Three-dimensional (3D) genome; Hi-C; Lamin-associated domain (LAD); Laminopathy; Modeling; Nuclear lamin; Topologically-associated domain (TAD);
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摘要
Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.
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