Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Twins: A deep learning method for replicate-based conformation contact map analysis.

ABSTRACT: The organisation of the genome in nuclear space is an important frontier of biology. Chromosome conformation capture methods such as Hi-C and Micro-C produce genome-wide chromatin contact maps that provide rich data containing quantitative and qualitative information about genome architecture. Most conventional approaches to genome-wide chromosome conformation capture data are limited to the analysis of pre-defined features, and may therefore miss important biological information. One constraint is that biologically important features can be masked by high levels of technical noise in the data. Here we introduce Twins, a replicate-based method for deep learning from chromatin conformation contact maps. Using a Siamese network configuration, Twins learns to distinguish technical noise from biological variation and outperforms image similarity metrics across a range of biological systems. Features extracted by Twins from Hi-C maps after perturbation of cohesin and CTCF reflect the distinct biological functions of cohesin and CTCF in the formation of domains and boundaries, respectively. Twins distance metrics are biologically meaningful, as they mirror the density of cohesin and CTCF binding. Taken together, these properties make Twins an powerful tool for the exploration of chromosome conformation capture data, such as Hi-C capture Hi-C, and Micro-C.

ORGANISM(S): Mus musculus

PROVIDER: GSE233377 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Cell type specificity of chromatin organization mediated by CTCF and cohesin

Project description:CTCF sites are abundant in the genomes of diverse species but their function is enigmatic. We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the β-globin locus and flanking olfactory receptor genes. Although CTCF occupies these sites in both erythroid K562 cells and fibroblast 293T cells, the long-range interaction frequencies among the sites are highly cell type specific, revealing a more densely clustered organization in the absence of globin gene activity. Both CTCF and cohesins are required for the cell-type-specific chromatin conformation. Furthermore, loss of the organizational loops in K562 cells through reduction of CTCF with shRNA results in acquisition of repressive histone marks in the globin locus and reduces globin gene expression, whereas silent flanking olfactory receptor genes are unaffected. These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function. Comparison of CTCF binding in K562 and 293T cells using ChIP-chip. 3 replicates each cell type, ChIP and input DNA for each replicate.

2011-01-13 | E-GEOD-26507 | biostudies-arrayexpress

Single cell Hi-C reveals cell-to-cell variability in chromosome structure

Project description:Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single cell Hi-C, combined with genome-wide statistical analysis and structural modeling of single copy X chromosomes, to show that individual chromosomes maintain domain organisation at the megabase scale, but show variable cell-to-cell chromosome territory structures at larger scales. Despite this structural stochasticity, localisation of active gene domains to boundaries of territories is a hallmark of chromosomal conformation, affecting most domains in most nuclei. Single cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organisation underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns. Mouse Th1 single-cell Hi-C maps were produced and paired-end sequenced. 10 single-cell samples and a multi-sample pool together with a population Hi-C sample are included.

2013-09-26 | E-GEOD-48262 | biostudies-arrayexpress

Conformation of sister chromatids in the replicated human genome

Project description:The three-dimensional organization of the genome supports regulated gene expression, recombination, DNA repair, and chromosome segregation during mitosis. Chromosome conformation capture (Hi-C) has revealed a complex genomic landscape of internal chromosome structures in vertebrate cells yet how sister chromatids topologically interact in replicated chromosomes has remained elusive due to their identical sequences. Here, we present sister-chromatid-sensitive Hi-C (scsHi-C) based on nascent DNA labeling with 4-thio-thymidine. Genome-wide conformation maps of human chromosomes revealed that sister chromatid pairs interact most frequently at the boundaries of topologically associating domains (TADs). Continuous loading of a dynamic cohesin pool separates sister-chromatid pairs inside TADs and is required to focus sister chromatid contacts at TAD boundaries. We identified a subset of TADs that are overall highly paired, characterized by facultative heterochromatin, as well as insulated topological domains that form separately within individual sister chromatids. The rich pattern of sister chromatid topologies and our scsHi-C technology will make it possible to dissect how physical interactions between identical DNA molecules contribute to DNA repair, gene expression, chromosome segregation, and potentially other biological processes.

2020-06-12 | GSE152373 | GEO

Chromosome Conformation of Human Fibroblasts Grown in 3-Dimensional Spheroids

Project description:In the study of interphase chromosome organization, genome-wide chromosome conformation capture (Hi-C) maps are often generated using 2-dimensional (2D) monolayer cultures. These 2D cells have morphological deviations from cells that exist in 3-dimensional (3D) tissues in vivo, and may not maintain the same chromosome conformation. We used Hi-C maps to test the extent of differences in chromosome conformation between human fibroblasts grown in 2D cultures and those grown in 3D spheroids. Significant differences in chromosome conformation were found between 2D cells and those grown in spheroids. Intra-chromosomal interactions were generally increased in spheroid cells, with a few exceptions, while inter-chromosomal interactions were generally decreased. Overall, chromosomes located closer to the nuclear periphery had increased intra-chromosomal contacts in spheroid cells, while those located more centrally had decreased interactions. This study highlights the necessity to conduct studies on the topography of the interphase nucleus under conditions that mimic an in vivo environment.

2016-01-26 | GSE77237 | GEO

Cell type specificity of chromatin organization mediated by CTCF and cohesin

2011-01-13 | GSE26507 | GEO

Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes

Project description:We recently used in situ Hi-C to create kilobase-resolution 3D maps of mammalian genomes. Here, we combine these with new Hi-C, microscopy, and genome-editing experiments to study the physical structure of chromatin fibers, domains, and loops. We find that the observed contact domains are inconsistent with the equilibrium state for an ordinary condensed polymer. Combining Hi-C data and novel mathematical theorems, we show that contact domains are also not consistent with a fractal globule. Instead, we use physical simulations to study two models of genome folding. In one, intermonomer attraction during polymer condensation leads to formation of an anisotropic "tension globule." In the other, CTCF and cohesin act together to extrude loops during interphase. Both models are consistent with the observed contact domains and with the observation that contact domains tend to form inside loops. However, the extrusion model explains a far wider array of observations, such as why loops tend not to overlap and why the CTCF-binding motifs at pairs of loop anchors lie in the convergent orientation. Finally, we perform 13 genome-editing experiments examining the effect of altering CTCF-binding sites on chromatin folding. The convergent rule correctly predicts the affected loop in every case. Moreover, the extrusion model accurately predicts in silico the 3D maps resulting from each experiment using only the location of CTCF-binding sites in the WT. Thus, we show that it is possible to disrupt, restore, and move loops and domains using targeted mutations as small as a single base pair. in situ Hi-C and HYbrid Capture Hi-C (Hi-C2) were used to probe the three-dimensional structure of the genome in two different human cell types before and after genome editing.

2015-10-23 | E-GEOD-74072 | biostudies-arrayexpress

Dynamic and stable enhancer-promoter contacts regulate terminal differentiation [UMI-4C]

Project description:Genome-wide chromosome conformation capture (Hi-C) and promoter-capture Hi-C (CHi-C) were performed during epidermal differentiation. These data indicate that dynamic and constitutive enhancer-promoter contacts combine to control gene induction during differentiation and that chromosome conformation enables discovery of new TFs with distinct roles in this process.

2017-06-28 | GSE95098 | GEO

Dynamic and stable enhancer-promoter contacts regulate terminal differentiation [RNA-Seq]

2017-06-28 | GSE84661 | GEO

Dynamic and stable enhancer-promoter contacts regulate terminal differentiation [HiC_CHiC]

2017-06-28 | GSE84660 | GEO

Dynamic and stable enhancer-promoter contacts regulate terminal differentiation [ChIP-Seq]

2017-06-28 | GSE84657 | GEO