Publications
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Rossini, Roberto; Oshaghi, Mohammadsaleh; Nekrasov, Maxim; Bellanger, Aurélie Nathalie Pascale; Domaschenz, Renae & Dijkwel, Yasmin
[Show all 13 contributors for this article]
(2025).
Loss of multilevel 3D genome organization during breast cancer progression.
Genome Research.
ISSN 1088-9051.
p. 1–18.
doi:
10.1101/gr.280791.125.
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Breast cancer entails intricate alterations in genome organization and expression. However, how three-dimensional (3D) chromatin structure changes in the progression from a normal to a breast cancer malignant state remains unknown. To address this, we have conducted an analysis combining Hi-C data with lamina-associated domains (LADs), epigenomic marks, and gene expression in an in vitro model of breast cancer progression. Our results reveal that although the fundamental properties of topologically associating domains (TADs) are overall maintained, significant changes occur in the organization of compartments and subcompartments. These changes are closely correlated with alterations in the expression of oncogenic genes. We also observe a restructuring of TAD–TAD interactions, coinciding with a loss of spatial compartmentalization and radial positioning of the 3D genome. Notably, we identify a previously unrecognized interchromosomal insertion event, wherein a locus on Chromosome 8 housing the MYC oncogene is inserted into a highly active subcompartment on Chromosome 10. This insertion is accompanied by the formation of de novo enhancer contacts and activation of MYC , illustrating how structural genomic variants can alter the 3D genome during oncogenesis. In summary, our findings provide evidence for the loss of genome organization at multiple scales during breast cancer progression, revealing novel relationships between genome 3D structure and oncogenic processes.
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Raffo, Andrea; Rossini, Roberto & Paulsen, Jonas
(2025).
StripePy: fast and robust characterization of architectural stripes.
Bioinformatics.
ISSN 1367-4803.
41(6).
doi:
10.1093/bioinformatics/btaf351.
Full text in Research Archive
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Motivation
Architectural stripes in Hi-C and related data are crucial for gene regulation, development, and DNA repair. Despite their importance, few tools exist for automatic stripe detection.
Results
We introduce StripePy, which leverages computational geometry methods to identify and analyze architectural stripes in contact maps from Chromosome Conformation Capture experiments like Hi-C and Micro-C. StripePy outperforms existing tools, as shown through tests on various datasets and a newly developed simulated benchmark, StripeBench, providing a valuable resource for the community.
Availability and implementation
StripePy is released to the public as an open-source, MIT-licensed Python application. StripePy source code is hosted on GitHub at https://github.com/paulsengroup/StripePy and is archived on Zenodo. StripePy can be easily installed from source or PyPI using pip and from Bioconda using conda. Containerized versions of StripePy are regularly published on DockerHub.
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Rossini, Roberto & Paulsen, Jonas
(2024).
hictk: blazing fast toolkit to work with .hic and .cool files.
Bioinformatics.
ISSN 1367-4803.
40(7).
doi:
10.1093/bioinformatics/btae408.
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Motivation Hi-C is gaining prominence as a method for mapping genome organization. With declining sequencing costs and a growing demand for higher-resolution data, efficient tools for processing Hi-C datasets at different resolutions are crucial. Over the past decade, the .hic and Cooler file formats have become the de-facto standard to store interaction matrices produced by Hi-C experiments in binary format. Interoperability issues make it unnecessarily difficult to convert between the two formats and to develop applications that can process each format natively. Results We developed hictk, a toolkit that can transparently operate on .hic and .cool files with excellent performance. The toolkit is written in C++ and consists of a C++ library with Python and R bindings as well as CLI tools to perform common operations directly from the shell, including converting between .hic and .mcool formats. We benchmark the performance of hictk and compare it with other popular tools and libraries. We conclude that hictk significantly outperforms existing tools while providing the flexibility of natively working with both file formats without code duplication. Availability and implementation The hictk library, Python bindings and CLI tools are released under the MIT license as a multi-platform application available at github.com/paulsengroup/hictk. Pre-built binaries for Linux and macOS are available on bioconda. Python bindings for hictk are available on GitHub at github.com/paulsengroup/hictkpy, while R bindings are available on GitHub at github.com/paulsengroup/hictkR.
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Jayaprasad, Suvratha; Peona, Valentina; Ellerstrand, Simon; Rossini, Roberto; Bunikis, Ignas & Pettersson, Olga
[Show all 17 contributors for this article]
(2024).
Orthopteran Neo-Sex Chromosomes Reveal Dynamics of Recombination Suppression and Evolution of Supergenes.
Molecular Ecology.
ISSN 0962-1083.
33.
doi:
10.1111/mec.17567.
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The early evolution of sex chromosomes has remained obscure for more than a century. The Vandiemenella viatica species group of morabine grasshoppers is highly suited for studying the early stages of sex chromosome divergence and degeneration of the Y chromosome. This stems from the fact that neo-XY sex chromosomes have independently evolved multiple times by X-autosome fusions with different autosomes. Here, we generated new chromosome-level assemblies for two chromosomal races representing karyotypes with and without neo-sex chromosomes (P24XY and P24X0), and sequence data of a third chromosomal race with a different neo-XY chromosome system (P25XY). Interestingly, these two neo-XY chromosomal races are formed by different X-autosome fusions (involving chr1 and chrB, respectively), and we found that both neo-Y chromosomes have partly ceased to recombine with their neo-X counterpart. We show that the neo-XY chromosomes have diverged through accumulation of SNPs and structural mutations, and that many neo-Y-linked genes have degenerated since recombination ceased. However, the non-recombining regions of neo-Y chromosomes host non-degenerated genes crucial for sex determination, such as sex-lethal and transformer, alongside genes associated with spermatogenesis, fertility, and reproduction, illustrating their integrative role as a masculinizing supergene. Contrary to expectations, the neo-Y chromosomes showed (slightly) lower density of transposable elements (TEs) compared to other genomic regions. The study reveals the unique dynamics of young sex chromosomes, with evolution of recombination suppression and pronounced decay of (some) neo-sex chromosome genes, and provides a compelling case illustrating how chromosomal fusions and post-fusion mutational processes contribute to the evolution of supergenes.
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Rossini, Roberto; Kumar, Vipin; Mathelier, Anthony; Rognes, Torbjørn & Paulsen, Jonas
(2022).
MoDLE: high-performance stochastic modeling of DNA loop extrusion interactions.
Genome Biology.
ISSN 1465-6906.
23(1).
doi:
10.1186/s13059-022-02815-7.
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DNA loop extrusion emerges as a key process establishing genome structure and function. We introduce MoDLE, a computational tool for fast, stochastic modeling of molecular contacts from DNA loop extrusion capable of simulating realistic contact patterns genome wide in a few minutes. MoDLE accurately simulates contact maps in concordance with existing molecular dynamics approaches and with Micro-C data and does so orders of magnitude faster than existing approaches. MoDLE runs efficiently on machines ranging from laptops to high performance computing clusters and opens up for exploratory and predictive modeling of 3D genome structure in a wide range of settings.
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View all works in NVA
Published
Oct. 2, 2020 11:05 AM
- Last modified
Nov. 30, 2022 2:44 PM
