2018
DOI: 10.1038/s41588-018-0098-8
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Polymer physics predicts the effects of structural variants on chromatin architecture

Abstract: Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and cause disease. However, the prediction of such effects remains a challenge. Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and … Show more

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Cited by 193 publications
(320 citation statements)
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“…Those genomic regions play a key role during cell differentiation and tissue development in mammals and structural variants in the loci are linked to human congenital diseases (Franke et al, ; Lupiáñez et al, and references therein). The SBS model of the loci was shown to reproduce Hi‐C data with good accuracy (Figure a, Chiariello et al, , Bianco et al, ). In fact, the contact frequency matrices derived from the simulated ensembles of 3D conformations of the different loci have a comparatively high Pearson, r , and distance corrected Pearson correlation coefficient, r ′ ( r ′ accounts for trivial genomic proximity effects, Bianco et al, ) with corresponding experimental Hi‐C matrices, ranging around r = 0.95 and r ′ = 0.60, respectively, below and above the scale of TADs.…”
Section: The Strings and Binders Modelmentioning
confidence: 89%
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“…Those genomic regions play a key role during cell differentiation and tissue development in mammals and structural variants in the loci are linked to human congenital diseases (Franke et al, ; Lupiáñez et al, and references therein). The SBS model of the loci was shown to reproduce Hi‐C data with good accuracy (Figure a, Chiariello et al, , Bianco et al, ). In fact, the contact frequency matrices derived from the simulated ensembles of 3D conformations of the different loci have a comparatively high Pearson, r , and distance corrected Pearson correlation coefficient, r ′ ( r ′ accounts for trivial genomic proximity effects, Bianco et al, ) with corresponding experimental Hi‐C matrices, ranging around r = 0.95 and r ′ = 0.60, respectively, below and above the scale of TADs.…”
Section: The Strings and Binders Modelmentioning
confidence: 89%
“…Further progresses from polymer physics can shed light on such molecular mechanisms and their implications in gene regulation. By those advancements, polymer models have been used to predict the effects of structural variants on the 3D organization of chromatin loci and the link with their associated phenotype (Bianco et al, ). Hopefully, the progress in our understanding of chromosome architecture can help developing novel approaches to tackle diseases linked to chromatin misfolding, such as congenital disorders and cancer (Lupiáñez et al, ; Valton & Dekker, ; Weischenfeldt et al, ).…”
Section: Discussionmentioning
confidence: 99%
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