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Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE92294 | GEO | 2018/02/12

REPOSITORIES: GEO

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Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture (human)

Project description:Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and consecutive disease. However, the prediction of such effects remains a challenge. Here we present a polymer physics based approach (PRISMR) to model chromatin folding and to predict enhancer-promoter contacts. Using the Epha4 locus as a model, the effects of pathogenic SVs were predicted in-silico and compared to published Hi-C and capture Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolutes the folding complexity of the studied locus, and identifies SV-induced alterations of 3D genome organization in the homozygous as well as the heterozygous state. Our method accurately predicts the specific sites of ectopic chromatin contacts that produce extensive rewiring of regulatory interactions, causing disease by gene misexpression. PRISMR can be used to predict interactions in silico thereby providing a tool for analyzing the disease causing potential of SVs.

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