Integrative genome modeling platform reveals essentiality of rare contact events in 3D genome organizations

• DOI: 10.1038/s41592-022-01527-x
• Publication Date: 2022-07-11T16:08:05Z
• Authors: Lorenzo Boninsegna; Asli Yildirim; Guido Polles; Yuxiang Zhan; Sofia A. Quinodoz; Elizabeth H. Finn; Mitchell Guttman; Xianghong Jasmine...; Frank Alber
• Keywords: Cell Nucleus; 0303 health sciences; 03 medical and health sciences; Genome; 610; Article; Chromatin; Chromosomes

Abstract A multitude of sequencing-based and microscopy technologies provide the means to unravel relationship between three-dimensional organization genomes key regulatory processes genome function. Here, we develop a multimodal data integration approach produce populations single-cell structures that are highly predictive for nuclear locations genes bodies, local chromatin compaction spatial segregation functionally related chromatin. We demonstrate can compensate systematic errors in some greatly increase accuracy coverage structure models. also show alternative combinations different orthogonal sources converge models with similar power. Moreover, our study reveals contributions low-frequency (‘rare’) interchromosomal contacts accurately predicting global architecture, including positioning chromosomes. Overall, results highlight benefits analysis, available through Integrative Genome Modeling software package.