scholarly journals CSynth: an interactive modelling and visualization tool for 3D chromatin structure

2020 ◽  
Author(s):  
Stephen Todd ◽  
Peter Todd ◽  
Simon J McGowan ◽  
James R Hughes ◽  
Yasutaka Kakui ◽  
...  
Keyword(s):  
3D Structure ◽  
Chromosome Conformation Capture ◽  
Third Party ◽  
Supplementary Information ◽  
Chromosome Conformation ◽  
Web Based ◽  
3D Genome ◽  
Interactive 3D ◽  
Interactive Modelling ◽  
Capture Techniques

Abstract Motivation The 3D structure of chromatin in the nucleus is important for gene expression and regulation. Chromosome conformation capture techniques, such as Hi-C, generate large amounts of data showing interaction points on the genome but these are hard to interpret using standard tools. Results We have developed CSynth, an interactive 3D genome browser and real-time chromatin restraint-based modeller to visualize models of any chromosome conformation capture (3C) data. Unlike other modelling systems, CSynth allows dynamic interaction with the modelling parameters to allow experimentation and effects on the model. It also allows comparison of models generated from data in different tissues/cell states and the results of third-party 3D modelling outputs. In addition, we include an option to view and manipulate these complicated structures using Virtual Reality (VR) so scientists can immerse themselves in the models for further understanding. This VR component has also proven to be a valuable teaching and a public engagement tool. Availabilityand implementation CSynth is web based and available to use at https://csynth.org. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals CSynth: A Dynamic Modelling and Visualisation Tool for 3D Chromatin Structure

2019 ◽  
Author(s):  
Stephen Todd ◽  
Peter Todd ◽  
Simon J. McGowan ◽  
James R. Hughes ◽  
Yasutaka Kakui ◽  
...  
Keyword(s):  
Real Time ◽  
Chromatin Structure ◽  
High Performance ◽  
3D Structure ◽  
Dynamic Modelling ◽  
Third Party ◽  
Web Based ◽  
3D Genome ◽  
Time Interaction ◽  
Capture Techniques

AbstractThe 3D structure of chromatin in the nucleus is important for gene expression and regulation. Chromosomal conformation capture techniques, such as Hi-C, generate large amounts of data showing interaction points on the genome but these are hard to interpret using standard tools. We have developed CSynth, a high performance 3D genome browser and real time chromatin restraint-based modeller to visualise dynamic and interactive models of chromatin capture data. CSynth does its calculations in the GPU hence is much faster than existing modelling software to infer and visualise the chromatin structure which also allow real-time interaction with the modelling parameters. It also allows straightforward comparison of interaction data and the results of third party 3D modelling outputs. In addition we include an option to view and manipulate these complicated structures using Virtual Reality (VR) allowing scientists to immerse themselves in the models for further understanding. This VR component has also proven to be a valuable teaching and public engagement tool. CSynth is web based and available to use at http://csynth.org.

scholarly journals Computational methods for predicting 3D genomic organization from high-resolution chromosome conformation capture data

2020 ◽  
Vol 19 (4) ◽  
pp. 292-308 ◽  
Author(s):  
Kimberly MacKay ◽  
Anthony Kusalik
Keyword(s):  
High Resolution ◽  
Genome Organization ◽  
3D Structure ◽  
Likelihood Estimation ◽  
Genomic Region ◽  
Chromosome Conformation Capture ◽  
Computational Tools ◽  
Chromosome Conformation ◽  
Single Chromosome ◽  
3D Genome

Abstract The advent of high-resolution chromosome conformation capture assays (such as 5C, Hi-C and Pore-C) has allowed for unprecedented sequence-level investigations into the structure–function relationship of the genome. In order to comprehensively understand this relationship, computational tools are required that utilize data generated from these assays to predict 3D genome organization (the 3D genome reconstruction problem). Many computational tools have been developed that answer this need, but a comprehensive comparison of their underlying algorithmic approaches has not been conducted. This manuscript provides a comprehensive review of the existing computational tools (from November 2006 to September 2019, inclusive) that can be used to predict 3D genome organizations from high-resolution chromosome conformation capture data. Overall, existing tools were found to use a relatively small set of algorithms from one or more of the following categories: dimensionality reduction, graph/network theory, maximum likelihood estimation (MLE) and statistical modeling. Solutions in each category are far from maturity, and the breadth and depth of various algorithmic categories have not been fully explored. While the tools for predicting 3D structure for a genomic region or single chromosome are diverse, there is a general lack of algorithmic diversity among computational tools for predicting the complete 3D genome organization from high-resolution chromosome conformation capture data.

scholarly journals SisterC: A novel 3C-technique to detect chromatin interactions between and along sister chromatids

2020 ◽  
Author(s):  
Marlies E. Oomen ◽  
Adam K. Hedger ◽  
Jonathan K. Watts ◽  
Job Dekker
Keyword(s):  
Cell Cycle ◽  
Single Strand ◽  
Chromosome Conformation Capture ◽  
Brdu Incorporation ◽  
Chromosome Conformation ◽  
Strand Breaks ◽  
Chromatin Interactions ◽  
Sister Chromatids ◽  
Single Strand Breaks ◽  
Capture Techniques

Abstract Current chromosome conformation capture techniques are not able to distinguish sister chromatids. Here we describe the protocol of SisterC1: a novel Hi-C technique that leverages BrdU incorporation and UV/Hoechst-induced single strand breaks to identify interactions along and between sister chromatids. By synchronizing cells, BrdU is incorporated only on the newly replicated strand, which distinguishes the two sister chromatids2,3. This is followed by Hi-C4 of cells that can be arrested in different stages of the cell cycle, e.g. in mitosis. Before final amplification of the Hi-C library, strands containing BrdU are specifically depleted by UV/Hoechst treatment. SisterC libraries are then sequenced using 50bp paired end reads, followed by mapping using standard Hi-C processing tools. Interactions can then be assigned as inter- or intra-sister interactions based on read orientation.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

scholarly journals epiTAD: a web application for visualizing chromosome conformation capture data in the context of genetic epidemiology

2019 ◽  
Vol 35 (21) ◽  
pp. 4462-4464
Author(s):  
Jordan H Creed ◽  
Garrick Aden-Buie ◽  
Alvaro N Monteiro ◽  
Travis A Gerke
Keyword(s):  
Genetic Epidemiology ◽  
In Silico ◽  
Web Application ◽  
Large Scale ◽  
Source Code ◽  
Chromosome Conformation Capture ◽  
Chromosome Conformation ◽  
Web Based ◽  
Genome Wide ◽  
Public Data

Abstract Summary Complementary advances in genomic technology and public data resources have created opportunities for researchers to conduct multifaceted examination of the genome on a large scale. To meet the need for integrative genome wide exploration, we present epiTAD. This web-based tool enables researchers to compare genomic 3D organization and annotations across multiple databases in an interactive manner to facilitate in silico discovery. Availability and implementation epiTAD can be accessed at https://apps.gerkelab.com/epiTAD/ where we have additionally made publicly available the source code and a Docker containerized version of the application.

scholarly journals epiTAD: a web application for visualizing high throughput chromosome conformation capture data in the context of genetic epidemiology

2018 ◽  
Author(s):  
Jordan H. Creed ◽  
Garrick Aden-Buie ◽  
Alvaro N. Monteiro ◽  
Travis A. Gerke
Keyword(s):  
High Throughput ◽  
Genetic Epidemiology ◽  
In Silico ◽  
Web Application ◽  
Chromosome Conformation Capture ◽  
Chromosome Conformation ◽  
Web Based ◽  
Genome Wide ◽  
Public Data ◽  
Complex Scale

AbstractThe increasing availability of public data resources coupled with advancements in genomic technology has created greater opportunities for researchers to examine the genome on a large and complex scale. To meet the need for integrative genome wide exploration, we present epiTAD. This web-based tool enables researchers to compare genomic structures and annotations across multiple databases and platforms in an interactive manner in order to facilitate in silico discovery. epiTAD can be accessed at https://apps.gerkelab.com/epiTAD/.

scholarly journals ChiTaRS 5.0: the comprehensive database of chimeric transcripts matched with druggable fusions and 3D chromatin maps

2019 ◽  
Author(s):  
Deepak Balamurali ◽  
Alessandro Gorohovski ◽  
Rajesh Detroja ◽  
Vikrant Palande ◽  
Dorith Raviv-Shay ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Human Cancer ◽  
Salient Feature ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Chimeric Rnas ◽  
Chimeric Transcripts ◽  
Chimeric Rna ◽  
Public Datasets ◽  
Capture Techniques

Abstract Chimeric RNA transcripts are formed when exons from two genes fuse together, often due to chromosomal translocations, transcriptional errors or trans-splicing effect. While these chimeric RNAs produce functional proteins only in certain cases, they play a significant role in disease phenotyping and progression. ChiTaRS 5.0 (http://chitars.md.biu.ac.il/) is the latest and most comprehensive chimeric transcript repository, with 111 582 annotated entries from eight species, including 23 167 known human cancer breakpoints. The database includes unique information correlating chimeric breakpoints with 3D chromatin contact maps, generated from public datasets of chromosome conformation capture techniques (Hi–C). In this update, we have added curated information on druggable fusion targets matched with chimeric breakpoints, which are applicable to precision medicine in cancers. The introduction of a new section that lists chimeric RNAs in various cell-lines is another salient feature. Finally, using text-mining techniques, novel chimeras in Alzheimer's disease, schizophrenia, dyslexia and other diseases were collected in ChiTaRS. Thus, this improved version is an extensive catalogue of chimeras from multiple species. It extends our understanding of the evolution of chimeric transcripts in eukaryotes and contributes to the analysis of 3D genome conformational changes and the functional role of chimeras in the etiopathogenesis of cancers and other complex diseases.

scholarly journals GenomeDISCO: A concordance score for chromosome conformation capture experiments using random walks on contact map graphs

2017 ◽  
Author(s):  
Oana Ursu ◽  
Nathan Boley ◽  
Maryna Taranova ◽  
Y.X. Rachel Wang ◽  
Galip Gurkan Yardimci ◽  
...  
Keyword(s):  
Random Walks ◽  
Critical Role ◽  
Three Dimensional ◽  
Cell Types ◽  
Chromosome Conformation Capture ◽  
Supplementary Information ◽  
Contact Map ◽  
Chromosome Conformation ◽  
Contact Maps ◽  
Map Graphs

AbstractMotivationThe three-dimensional organization of chromatin plays a critical role in gene regulation and disease. High-throughput chromosome conformation capture experiments such as Hi-C are used to obtain genome-wide maps of 3D chromatin contacts. However, robust estimation of data quality and systematic comparison of these contact maps is challenging due to the multi-scale, hierarchical structure of chromatin contacts and the resulting properties of experimental noise in the data. Measuring concordance of contact maps is important for assessing reproducibility of replicate experiments and for modeling variation between different cellular contexts.ResultsWe introduce a concordance measure called GenomeDISCO (DIfferences between Smoothed COntact maps) for assessing the similarity of a pair of contact maps obtained from chromosome conformation capture experiments. The key idea is to smooth contact maps using random walks on the contact map graph, before estimating concordance. We use simulated datasets to benchmark GenomeDISCO’s sensitivity to different types of noise that affect chromatin contact maps. When applied to a large collection of Hi-C datasets, GenomeDISCO accurately distinguishes biological replicates from samples obtained from different cell types. GenomeDISCO also generalizes to other chromosome conformation capture assays, such as HiChIP.AvailabilitySoftware implementing GenomeDISCO is available at https://github.com/kundajelab/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

2019 ◽  
Author(s):  
Oluwatosin Oluwadare ◽  
Max Highsmith ◽  
Jianlin Cheng
Keyword(s):  
Structure Prediction ◽  
Biological Activities ◽  
Genome Structure ◽  
3D Structure ◽  
Three Dimensional ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Reconstruction Methods ◽  
A Genome ◽  
Structure Reconstruction

ABSTRACTAdvances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB

scholarly journals Understanding 3D Genome Organization and Its Effect on Transcriptional Gene Regulation Under Environmental Stress in Plant: A Chromatin Perspective

2021 ◽  
Vol 9 ◽  
Author(s):  
Suresh Kumar ◽  
Simardeep Kaur ◽  
Karishma Seem ◽  
Santosh Kumar ◽  
Trilochan Mohapatra
Keyword(s):  
Gene Expression ◽  
Environmental Stress ◽  
Genome Organization ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Regulatory Elements ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Chromatin Architecture ◽  
Capture Techniques

The genome of a eukaryotic organism is comprised of a supra-molecular complex of chromatin fibers and intricately folded three-dimensional (3D) structures. Chromosomal interactions and topological changes in response to the developmental and/or environmental stimuli affect gene expression. Chromatin architecture plays important roles in DNA replication, gene expression, and genome integrity. Higher-order chromatin organizations like chromosome territories (CTs), A/B compartments, topologically associating domains (TADs), and chromatin loops vary among cells, tissues, and species depending on the developmental stage and/or environmental conditions (4D genomics). Every chromosome occupies a separate territory in the interphase nucleus and forms the top layer of hierarchical structure (CTs) in most of the eukaryotes. While the A and B compartments are associated with active (euchromatic) and inactive (heterochromatic) chromatin, respectively, having well-defined genomic/epigenomic features, TADs are the structural units of chromatin. Chromatin architecture like TADs as well as the local interactions between promoter and regulatory elements correlates with the chromatin activity, which alters during environmental stresses due to relocalization of the architectural proteins. Moreover, chromatin looping brings the gene and regulatory elements in close proximity for interactions. The intricate relationship between nucleotide sequence and chromatin architecture requires a more comprehensive understanding to unravel the genome organization and genetic plasticity. During the last decade, advances in chromatin conformation capture techniques for unravelling 3D genome organizations have improved our understanding of genome biology. However, the recent advances, such as Hi-C and ChIA-PET, have substantially increased the resolution, throughput as well our interest in analysing genome organizations. The present review provides an overview of the historical and contemporary perspectives of chromosome conformation capture technologies, their applications in functional genomics, and the constraints in predicting 3D genome organization. We also discuss the future perspectives of understanding high-order chromatin organizations in deciphering transcriptional regulation of gene expression under environmental stress (4D genomics). These might help design the climate-smart crop to meet the ever-growing demands of food, feed, and fodder.

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