Dataset Information

HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP.

ABSTRACT: Recent genome-wide chromosome conformation capture assays such as Hi-C and HiChIP have vastly expanded the resolution and throughput with which we can study 3D genomic architecture and function. Here, we present HiC-DC+, a software tool for Hi-C/HiChIP interaction calling and differential analysis using an efficient implementation of the HiC-DC statistical framework. HiC-DC+ integrates with popular preprocessing and visualization tools and includes topologically associating domain (TAD) and A/B compartment callers. We found that HiC-DC+ can more accurately identify enhancer-promoter interactions in H3K27ac HiChIP, as validated by CRISPRi-FlowFISH experiments, compared to existing methods. Differential HiC-DC+ analyses of published HiChIP and Hi-C data sets in settings of cellular differentiation and cohesin perturbation systematically and quantitatively recovers biological findings, including enhancer hubs, TAD aggregation, and the relationship between promoter-enhancer loop dynamics and gene expression changes. HiC-DC+ therefore provides a principled statistical analysis tool to empower genome-wide studies of 3D chromatin architecture and function.

SUBMITTER: Sahin M

PROVIDER: S-EPMC8184932 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP.

Sahin Merve M Wong Wilfred W Zhan Yingqian Y Van Deynze Kinsey K Koche Richard R Leslie Christina S CS

Nature communications 20210607 1

Recent genome-wide chromosome conformation capture assays such as Hi-C and HiChIP have vastly expanded the resolution and throughput with which we can study 3D genomic architecture and function. Here, we present HiC-DC+, a software tool for Hi-C/HiChIP interaction calling and differential analysis using an efficient implementation of the HiC-DC statistical framework. HiC-DC+ integrates with popular preprocessing and visualization tools and includes topologically associating domain (TAD) and A/B ...[more]

PMID: 34099725

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Project description:BackgroundChromatin conformation capture techniques have evolved rapidly over the last few years and have provided new insights into genome organization at an unprecedented resolution. Analysis of Hi-C data is complex and computationally intensive involving multiple tasks and requiring robust quality assessment. This has led to the development of several tools and methods for processing Hi-C data. However, most of the existing tools do not cover all aspects of the analysis and only offer few quality assessment options. Additionally, availability of a multitude of tools makes scientists wonder how these tools and associated parameters can be optimally used, and how potential discrepancies can be interpreted and resolved. Most importantly, investigators need to be ensured that slight changes in parameters and/or methods do not affect the conclusions of their studies.ResultsTo address these issues (compare, explore and reproduce), we introduce HiC-bench, a configurable computational platform for comprehensive and reproducible analysis of Hi-C sequencing data. HiC-bench performs all common Hi-C analysis tasks, such as alignment, filtering, contact matrix generation and normalization, identification of topological domains, scoring and annotation of specific interactions using both published tools and our own. We have also embedded various tasks that perform quality assessment and visualization. HiC-bench is implemented as a data flow platform with an emphasis on analysis reproducibility. Additionally, the user can readily perform parameter exploration and comparison of different tools in a combinatorial manner that takes into account all desired parameter settings in each pipeline task. This unique feature facilitates the design and execution of complex benchmark studies that may involve combinations of multiple tool/parameter choices in each step of the analysis. To demonstrate the usefulness of our platform, we performed a comprehensive benchmark of existing and new TAD callers exploring different matrix correction methods, parameter settings and sequencing depths. Users can extend our pipeline by adding more tools as they become available.ConclusionsHiC-bench consists an easy-to-use and extensible platform for comprehensive analysis of Hi-C datasets. We expect that it will facilitate current analyses and help scientists formulate and test new hypotheses in the field of three-dimensional genome organization.

Dataset Information

HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP.

Publications

HiC-DC+ enables systematic 3D interaction calls and differential analysis for Hi-C and HiChIP.

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