Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture
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PROVIDER: PRJNA357104 | ENA |
REPOSITORIES: ENA
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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.
2018-02-12 | GSE92291 | GEO
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.
2018-02-12 | GSE92290 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-02-12 | GSE92294 | GEO
Project description:Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture (human)
| PRJNA357108 | ENA
Project description:Polymer Physics Predicts the Effects of Structural Variants on Chromatin Architecture (mouse)
| PRJNA357107 | ENA
Project description:Structural characterization of ribosome variants
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Project description:Higher order chromatin structure is important for regulation of genes by distal regulatory sequences. Structural variants that alter 3D genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer. However, only a small minority of structural variants are associated with altered gene expression and it remains unclear why certain structural variants lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation. By analyzing Hi-C data from 92 cancer cell lines and patient samples, we identified loci affected by recurrent alterations to 3D genome structure, including oncogenes such as MYC, TERT, and CCND1. Using CRISPR/Cas9 genome engineering to generate de novo structural variants, we show that oncogene activity can be predicted using “Activity-by-Contact” models that consider partner region chromatin contacts and enhancer activity. However, Activity-by-Contact models are only predictive of specific subsets of genes in the genome, suggesting that different classes of genes engage in distinct modes of regulation by distal regulatory elements. These results indicate that structural variants that alter 3D genome organization are widespread in cancer genomes and begin to illustrate predictive rules for the consequences of structural variants on oncogene activation.
2022-10-04 | GSE147123 | GEO
Project description:While nucleotide-resolution maps of genomic structural variants (SVs) have provided insights into the origin and impact on phenotypic diversity in humans, comparable maps in nonhuman primates have thus far been lacking. Using massively parallel DNA sequencing we constructed fine-resolution, species-specific structural variation and segmental duplication maps for five chimpanzees, five orang-utans, and five rhesus macaques. The SV maps, comprising thousands of deletions, duplications, and mobile element insertions, revealed a high activity of retrotransposition in macaques. Non-allelic homologous recombination, linked with genomic architecture, primarily shaped the genomes of great apes resulting in different SV formation mechanism landscapes across species, with distinct functional consequences. Transcriptome analyses across nonhuman primates and humans revealed significant effects of species-specific gene duplications on gene expression, with these effects displaying remarkable diversity in direction and magnitude. Thirteen inter-species gene duplications coincided with the species-specific gain of expression in a new tissue, implicating these duplications in function acquisition. Agilent arrays were custom designed for probes to be relatively evenly spaced across the reference genomes of chimpanzee, orang-utan, and rhesus macaque. For each species 9 one million probe arrays were used to cover the autosomes and a single 400k probe array was used for the sex chromosomes.
2013-08-10 | E-GEOD-45741 | biostudies-arrayexpress
Project description:Linked-Read Sequencing to Resolve Complex Structural Variants
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Project description:Linked-Read Sequencing to Resolve Complex Structural Variants
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