Hi-C analyses with GENOVA: a case study with cohesin variants
Open accessPublished version of a preprint
Abstract
Conformation capture-approaches like Hi-C can elucidate chromosome structure at a genome-wide scale. Hi-C datasets are large and require specialised software. Here, we present GENOVA: a user-friendly software package to analyse and visualise chromosome conformation capture (3C) data. GENOVA is an R-package that includes the most common Hi-C analyses, such as compartment and insulation score analysis. It can create annotated heatmaps to visualise the contact frequency at a specific locus and aggregate Hi-C signal over user-specified genomic regions such as ChIP-seq data. Finally, our package supports output from the major mapping-pipelines. We demonstrate the capabilities of GENOVA by analysing Hi-C data from HAP1 cell lines in which the cohesin-subunits SA1 and SA2 were knocked out. We find that ΔSA1 cells gain intra-TAD interactions and increase compartmentalisation. ΔSA2 cells have longer loops and a less compartmentalised genome. These results suggest that cohesinSA1 forms longer loops, while cohesinSA2 plays a role in forming and maintaining intra-TAD interactions. Our data supports the model that the genome is provided structure in 3D by the counter-balancing of loop formation on one hand, and compartmentalization on the other hand. By differentially controlling loops, cohesinSA1 and cohesinSA2 therefore also affect nuclear compartmentalization. We show that GENOVA is an easy to use R-package, that allows researchers to explore Hi-C data in great detail.
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Independent Hi-C replicates (up to two) were merged for each condition only after ascertaining overall similarity of each replicate using P(s) curves and aggregate peak analysis.
“After ascertaining the overall similarity of each replicate using either cooltools (86) or Genova (87) [P(s) curves and aggregate peak analysis], the independent Hi-C replicates (up to two) were merged for each condition.”
From Synergy between regulatory elements can render cohesin dispensable for distal enhancer function (2026) · cites this paper as [87]
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Large-scale chromatin reorganization reactivates placenta-specific genes that drive cellular aging
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Synergy between regulatory elements can render cohesin dispensable for distal enhancer function
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Self-citation
- Authors
- van der Weide, R. H., van den Brand, T., Haarhuis, J. H. I., Teunissen, H., Rowland, B. D., & de Wit, E.
- Affiliations
- Division of Gene Regulation, Oncode Institute and The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
- The Netherlands Cancer Institute (NL)
- Venue
- NAR Genomics and Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-04-09
- Volume
- 3
- Issue
- 2
- Pages
- lqab040-lqab040
- ISSN
- 2631-9268 (ISSN-L)
- PMC
- PMC8140737
- OpenAlex
- W3165253641
- Cited by
- 161
- References
- 59
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 44 · 2023: 30 · 2022: 19 · 2021: 8
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NAR Genomics and Bioinformatics (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- ERC (637597, 772471)
- Dutch Cancer Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Hi-C, Genoa, chromosome conformation capture, cohesin, topologically associating domains, nuclear compartmentalization, 3D genome organization, R package, loop formation
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