Improved inference of chromosome conformation from images of labeled loci.
Ontology highlight
ABSTRACT:
SUBMITTER: Ross BC
PROVIDER: S-EPMC6644830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Methods for analyzing chromosome conformation in mammalian cells are either low resolution or low throughput and are technically challenging. In next-generation (NG) Capture-C, we have redesigned the Capture-C method to achieve unprecedented levels of sensitivity and reproducibility. NG Capture-C can be used to analyze many genetic loci and samples simultaneously. High-resolution data can be produced with as few as 100,000 cells, and single-nucleotide polymorphisms can be used to generate allele-specific tracks. The method is straightforward to perform and should greatly facilitate the investigation of many questions related to gene regulation as well as the functional dissection of traits examined in genome-wide association studies.
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Project description:Current methods for analysing chromosome conformation in mammalian cells are either insensitive and low resolution or low throughput. Since the methods are expensive and relatively difficult to perform and analyse they are not widely used outside of specialised laboratories. Here we have re-designed the Capture-C method producing a new approach, called next generation (NG) Capture-C, which solves most of the current setbacks in analysing chromosome conformation. NG Capture-C produces unprecedented levels of sensitivity and reproducibility, which can be used to analyse any number of genetic loci and/or many samples in a single experiment. NG Capture is straightforward to perform, requiring only standard reagents and access to basic next generation sequencing platforms. The complete and detailed protocol presented here, with new publically available tools for library design and data analysis, will allow most laboratories to analyse chromatin conformation at levels of sensitivity and throughput that were previously impossible.
2015-11-16 | GSE67959 | GEO
Project description:Brassica rapa comprises several important cultivated vegetables and oil crops. Current reference genome assemblies of Brassica rapa are quite fragmented and not highly contiguous, thereby limiting extensive genetic and genomic analyses. Here, we report an improved assembly of the B. rapa genome (v3.0) using single-molecule sequencing, optical mapping, and chromosome conformation capture technologies (Hi-C). Relative to the previous reference genomes, our assembly features a contig N50 size of 1.45?Mb, representing a ~30-fold improvement. We also identified a new event that occurred in the B. rapa genome ~1.2 million years ago, when a long terminal repeat retrotransposon (LTR-RT) expanded. Further analysis refined the relationship of genome blocks and accurately located the centromeres in the B. rapa genome. The B. rapa genome v3.0 will serve as an important community resource for future genetic and genomic studies in B. rapa. This resource will facilitate breeding efforts in B. rapa, as well as comparative genomic analysis with other Brassica species.
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Project description:The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture-on-chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses co-localize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNaseI hypersensitive sites which represent the entire cell type-specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and suggest that a major force in shaping genome architecture is the repertoire of chromatin binding factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general, and to permit efficient gene regulation. Fourteen arrays total: Eight microarrays from individual biological replicates, and six microarrays each from a pool of two biological replicates. This submission represents the chromosome conformation capture-on-chip component of the study. The expression data are included in GSE26189.
2011-04-21 | E-GEOD-27115 | biostudies-arrayexpress
Project description:The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture-on-chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses co-localize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNaseI hypersensitive sites which represent the entire cell type-specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and suggest that a major force in shaping genome architecture is the repertoire of chromatin binding factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general, and to permit efficient gene regulation.
2011-04-21 | GSE27115 | GEO
Project description:Chemical cross-linking and DNA sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to 10-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes.
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Project description:[This corrects the article DOI: 10.1038/s41438-018-0071-9.].
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Project description:BackgroundWe present ARCHes, a fast and accurate haplotype-based approach for inferring an individual's ancestry composition. Our approach works by modeling haplotype diversity from a large, admixed cohort of hundreds of thousands, then annotating those models with population information from reference panels of known ancestry.ResultsThe running time of ARCHes does not depend on the size of a reference panel because training and testing are separate processes, and the inferred population-annotated haplotype models can be written to disk and reused to label large test sets in parallel (in our experiments, it averages less than one minute to assign ancestry from 32 populations using 10 CPU). We test ARCHes on public data from the 1000 Genomes Project and the Human Genome Diversity Project (HGDP) as well as simulated examples of known admixture.ConclusionsOur results demonstrate that ARCHes outperforms RFMix at correctly assigning both global and local ancestry at finer population scales regardless of the amount of population admixture.
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Project description:Modular domains of long non-coding RNAs can serve as scaffolds to bring distant regions of the linear genome into spatial proximity. Here, we present HiChIRP, a method leveraging bio-orthogonal chemistry and optimized chromosome conformation capture conditions, which enables interrogation of chromatin architecture focused around a specific RNA of interest down to approximately ten copies per cell. HiChIRP of three nuclear RNAs reveals insights into promoter interactions (7SK), telomere biology (telomerase RNA component) and inflammatory gene regulation (lincRNA-EPS).
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Project description:Chemical cross-linking and high-throughput sequencing have revealed regions of intra-chromosomal interaction, referred to as topologically associating domains (TADs), interspersed with regions of little or no such interaction, in interphase nuclei. We find that TADs and the regions between them correspond with the bands and interbands of polytene chromosomes of Drosophila. We further establish the conservation of TADs between polytene and diploid cells of Drosophila. From direct measurements on light micrographs of polytene chromosomes, we then deduce the states of chromatin folding in the diploid cell nucleus. Two states of chromatin folding, fully extended fibers containing regulatory regions and promoters, and fibers condensed up to ten-fold containing coding regions of active genes, constitute the euchromatin of the nuclear interior. Chromatin fibers condensed up to 30-fold, containing coding regions of inactive genes, represent the heterochromatin of the nuclear periphery. A convergence of molecular analysis with direct observation thus reveals the architecture of interphase chromosomes. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-11-05 | E-GEOD-72512 | biostudies-arrayexpress