scholarly journals Effective Cancer Detection Using Higher-Order Genome Architecture and Chromatin Interactions

2021 ◽  
Author(s):  
My Chung
Keyword(s):  
Cancer Detection ◽  
Higher Order ◽  
Genome Architecture ◽  
Chromatin Interactions

scholarly journals An integrative approach for fine-mapping chromatin interactions

2019 ◽  
Vol 36 (6) ◽  
pp. 1704-1711
Author(s):  
Artur Jaroszewicz ◽  
Jason Ernst
Keyword(s):  
Gene Regulation ◽  
High Resolution ◽  
Biological Significance ◽  
Computational Method ◽  
Supplementary Information ◽  
Integrative Approach ◽  
Genome Architecture ◽  
Open Chromatin ◽  
Chromatin Interactions ◽  
Genome Wide

Abstract Motivation Chromatin interactions play an important role in genome architecture and gene regulation. The Hi-C assay generates such interactions maps genome-wide, but at relatively low resolutions (e.g. 5-25 kb), which is substantially coarser than the resolution of transcription factor binding sites or open chromatin sites that are potential sources of such interactions. Results To predict the sources of Hi-C-identified interactions at a high resolution (e.g. 100 bp), we developed a computational method that integrates data from DNase-seq and ChIP-seq of TFs and histone marks. Our method, χ-CNN, uses this data to first train a convolutional neural network (CNN) to discriminate between called Hi-C interactions and non-interactions. χ-CNN then predicts the high-resolution source of each Hi-C interaction using a feature attribution method. We show these predictions recover original Hi-C peaks after extending them to be coarser. We also show χ-CNN predictions enrich for evolutionarily conserved bases, eQTLs and CTCF motifs, supporting their biological significance. χ-CNN provides an approach for analyzing important aspects of genome architecture and gene regulation at a higher resolution than previously possible. Availability and implementation χ-CNN software is available on GitHub (https://github.com/ernstlab/X-CNN). Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals GAMtools: an automated pipeline for analysis of Genome Architecture Mapping data

2017 ◽  
Author(s):  
Robert A. Beagrie ◽  
Markus Schueler
Keyword(s):  
Next Generation Sequencing Data ◽  
Genome Architecture ◽  
Sequencing Data ◽  
Cell Nuclei ◽  
Automated Mapping ◽  
Chromatin Interactions ◽  
Genome Wide ◽  
Quality Control Metrics ◽  
Genomic Regions ◽  
Analytical Tools

AbstractGenome Architecture Mapping (GAM) is a recently developed method for mapping chromatin interactions genome-wide. GAM is based on sequencing genomic DNA extracted from thin cryosections of cell nuclei. As a new approach, GAM datasets require specialized analytical tools and approaches. Here we present GAMtools, a pipeline for analysing GAM datasets. GAMtools covers the automated mapping of raw next-generation sequencing data generated by GAM, detection of genomic regions present in each nuclear slice, calculation of quality control metrics, generation of inferred proximity matrices, plotting of heatmaps and detection of genomic features for which chromatin interactions are enriched/depleted.

Being in a loop: how long non-coding RNAs organise genome architecture

2019 ◽  
Vol 63 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Giuseppina Pisignano ◽  
Ioanna Pavlaki ◽  
Adele Murrell
Keyword(s):  
Gene Expression ◽  
Chromatin Structure ◽  
Potential Role ◽  
Conclusive Evidence ◽  
Genome Architecture ◽  
Chromatin Interactions ◽  
In Trans ◽  
Non Coding Rnas ◽  
Expression Evidence ◽  
In Cis

Abstract Chromatin architecture has a significant impact on gene expression. Evidence in the last two decades support RNA as an important component of chromatin structure [Genes Dev. (2005) 19, 1635–1655; PLoS ONE (2007) 2, e1182; Nat. Genet. (2002) 30, 329–334]. Long non-coding RNAs (lncRNAs) are able to control chromatin structure through nucleosome positioning, interaction with chromatin re-modellers and chromosome looping. These functions are carried out in cis at the site of lncRNAs transcription or in trans at distant loci. While the evidence for a role in lncRNAs in regulating gene expression through chromatin interactions is increasing, there is still very little conclusive evidence for a potential role in looping organisation. Here, we review models for the involvement of lncRNAs in genome architecture and the experimental evidence to support them.

ATRX in chromatin assembly and genome architecture during development and disease

2011 ◽  
Vol 89 (5) ◽  
pp. 435-444 ◽  
Author(s):  
Nathalie G. Bérubé
Keyword(s):  
Gene Regulation ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Higher Order ◽  
Chromatin Assembly ◽  
Genome Architecture ◽  
Chromatin Conformation ◽  
Mammalian Development ◽  
Mitosis And Meiosis

The regulation of genome architecture is essential for a variety of fundamental cellular phenomena that underlie the complex orchestration of mammalian development. The ATP-dependent chromatin remodeling protein ATRX is emerging as a key regulatory component of nucleosomal dynamics and higher order chromatin conformation. Here we provide an overview of the role of ATRX at chromatin and during development, and discuss recent studies exposing a repertoire of ATRX functions at heterochromatin, in gene regulation, and during mitosis and meiosis. Exciting new progress on several fronts suggest that ATRX operates in histone variant deposition and in the modulation of higher order chromatin structure. Not surprisingly, dysfunction or absence of ATRX protein has devastating consequences on embryonic development and leads to human disease.

scholarly journals Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells

2020 ◽  
Author(s):  
Lei Chang ◽  
Mengfan Li ◽  
Shipeng Shao ◽  
Chen Li ◽  
Shanshan Ai ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Higher Order ◽  
Order Structure ◽  
Chromatin Dynamics ◽  
Lamin B1 ◽  
Chromatin Architecture ◽  
Chromatin Interactions ◽  
Molecular Machinery

Abstract The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.

scholarly journals MeCP2 and Chromatin Compartmentalization

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 878 ◽  
Author(s):  
Annika Schmidt ◽  
Hui Zhang ◽  
M. Cristina Cardoso
Keyword(s):  
Transcriptional Regulation ◽  
Rett Syndrome ◽  
Chromatin Structure ◽  
Binding Protein ◽  
Higher Order ◽  
Functional Domains ◽  
Genome Architecture

Methyl-CpG binding protein 2 (MeCP2) is a multifunctional epigenetic reader playing a role in transcriptional regulation and chromatin structure, which was linked to Rett syndrome in humans. Here, we focus on its isoforms and functional domains, interactions, modifications and mutations found in Rett patients. Finally, we address how these properties regulate and mediate the ability of MeCP2 to orchestrate chromatin compartmentalization and higher order genome architecture.

scholarly journals Probing multi-way chromatin interaction with hypergraph representation learning

2020 ◽  
Author(s):  
Ruochi Zhang ◽  
Jian Ma
Keyword(s):  
Genome Organization ◽  
Representation Learning ◽  
Higher Order ◽  
Computational Method ◽  
Chromatin Interaction ◽  
Interaction Data ◽  
3D Genome ◽  
Chromatin Interactions ◽  
Single Nucleus ◽  
And Function

AbstractAdvances in high-throughput mapping of 3D genome organization have enabled genome-wide characterization of chromatin interactions. However, proximity ligation based mapping approaches for pairwise chromatin interaction such as Hi-C cannot capture multi-way interactions, which are informative to delineate higher-order genome organization and gene regulation mechanisms at single-nucleus resolution. The very recent development of ligation-free chromatin interaction mapping methods such as SPRITE and ChIA-Drop has offered new opportunities to uncover simultaneous interactions involving multiple genomic loci within the same nuclei. Unfortunately, methods for analyzing multi-way chromatin interaction data are significantly underexplored. Here we develop a new computational method, called MATCHA, based on hypergraph representation learning where multi-way chromatin interactions are represented as hyperedges. Applications to SPRITE and ChIA-Drop data suggest that MATCHA is effective to denoise the data and make de novo predictions of multi-way chromatin interactions, reducing the potential false positives and false negatives from the original data. We also show that MATCHA is able to distinguish between multi-way interaction in a single nucleus and combination of pairwise interactions in a cell population. In addition, the embeddings from MATCHA reflect 3D genome spatial localization and function. MATCHA provides a promising framework to significantly improve the analysis of multi-way chromatin interaction data and has the potential to offer unique insights into higher-order chromosome organization and function.

Sign in / Sign up

Export Citation Format

Share Document