Abstract
Characterizing the genomes of living organisms increasingly involves extensive use of computational tools for data processing and analysis. During my PhD, I have developed and utilized computational tools to improve our understanding of how genomes are organized in three dimensions (3D). During my PhD, I developed MoDLE, a rapid computational tool that simulates a process known as DNA loop extrusion, a crucial biochemical process playing a key role in organizing the genome, regulating gene expression, and repairing DNA. Further, I developed hictk, a toolkit to efficiently process 3D genome mapping data such as Hi-C, enabling researchers to operate on multiple file formats, something that was not previously possible. Finally, in the last part of my PhD, I studied how the 3D genome is disorganized in breast cancer cells. From our analyses, we uncovered that the 3D genome organization is compromised during breast cancer progression, revealing a multi-level genome disorganization that disrupts oncogene regulation, potentially driving breast cancer progression. Taken together, my work highlights the importance of high-quality and high-performance computational tools, as these are crucial to characterizing biological processes such as the progression of cancer.
List of papers
Paper I. Rossini R., Kumar V., Mathelier A., Rognes T. and Paulsen J. “MoDLE: high-performance stochastic modeling of DNA loop extrusion interactions”. Genome Biology 23, 247 (2022) DOI: 10.1186/s13059-022-02815-7. The article is included in the thesis. Also available at: https://doi.org/10.1186/s13059‑022‑02815‑7 |
Paper II. Rossini R. and Paulsen J. “hictk: blazing fast toolkit to work with .hic and .cool files”. Submitted for publication. The paper is not available in DUO awaiting publishing. Preprint available in bioRxiv DOI: 10.1101/2023.11.26.568707 |
Paper III. Rossini R., Oshaghi M., Nekrasov M., Bellanger A., Domaschenz R., Dijkwel Y., Abdelhalim M., Collas P., Tremethick D. and Paulsen J. “Multi-level 3D genome organization deteriorates during breast cancer progression”. Submitted for publication. The paper is not available in DUO awaiting publishing. Preprint available in bioRxiv DOI: 10.1101/2023.11.26.568711 |