Research - 3D organization of the genome
I am developing computational tools to study the 3D organization of genomes, with the aim of understanding the relationship between structure and function in this highly dynamic and complex system. In the CollasLab, we are applying a multidisciplinary approach, by incorporating both Monte Carlo optimization and physics-based techniques, and validating the resulting predictions using molecular techniques such as FISH and imaging. We are particularly interested in the role of nuclear lamins in regulating the 3D structure and function of the human genome, both in contexts of stem cell differentiation, but also to understand disease processes resulting from genome misorganization.
Physical models of 3D genomes
I am collaborating with biophysicists Christian Micheletti at SISSA, and Marco Di Stefano at CNAG. Together, we recently published a paper in Scientific Reports where we present physical 3D models of full, diploid human genomes at unprecedented resolution (see video below). Our models revealed that many of the well-known functional properties of the human genome is in fact encoded into the "neighbour-maps" that connect the various parts of the genome together in 3D. Our paper was picked up by several science news networks, including Science Magazine. Our genomic models was selected as Biomedical Picture of the day on December 2nd 2016.
3D co-localization of genomic elements
During my PhD, I developed methods to infer statistically significant contacts between genomic regions. Together with scientists at the Department of Mathematics (Ingrid Glad, Ørnulf Borgan) and Tonje G Lien, and at the Institute of Informatics (Eivind Hovig (my PhD supervisor), Geir Kjetil Sandve, we developed methods to infer the statistical significance of 3D co-localization of selected genomic elements. These methods were later integrated into a set of web-tools called HiBrowse, which is based on the UiO-developed Genomic HyperBrowser. Several researchers at the Norwegian Computing Center, particularly Lars Holden and Marit Holden, have also been involved in these projects.
ChiaSig - Inference of significant contacts from ChIA-PET data
I am the developer of the ChiaSig tool, which allow for fast and accurate inference of significant interactions from ChIA-PET data, based on the non-central hyper-geometric distribution (NCHG).
MBO - Manifold based optimization for single-cell 3D genome reconstruction
I have been working together with Odin Gramstad to develop a manifold-based optimization algorithm to infer the 3D structure of genome structure in single cells, based on single-cell Hi-C data. The Matlab-code from this project can be downloaded here.
- Briand, Nolwenn; Guénantin, Anne-Claire; Jeziorowska, Dorota; Shah, Akshay; Mantecon, Matthieu; Capel, Emilie; Garcia, Maria; Oldenburg, Anja; Paulsen, Jonas; Hulot, Jean-Sébastien; Vigouroux, Corinne & Collas, Philippe (2018). The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks. Human Molecular Genetics. ISSN 0964-6906. 27(8), s 1447- 1459 . doi: 10.1093/hmg/ddy055
- Paulsen, Jonas; Liyakat Ali, Tharvesh Moideen & Collas, Philippe (2018). Computational 3D genome modeling using Chrom3D. Nature Protocols. ISSN 1754-2189. 13(5), s 1137- 1152 . doi: 10.1038/nprot.2018.009
- Garcia-Nieto, Pablo E; Schwartz, Erin K; King, Devin A; Paulsen, Jonas; Collas, Philippe; Herrera, Rafael E & Morrison, Ashby J (2017). Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis. EMBO Journal. ISSN 0261-4189. 36(19), s 2829- 2843 . doi: 10.15252/embj.201796717
- Paulsen, Jonas; Sekelja, Monika; Oldenburg, Anja; Barateau, Alice; Briand, Nolwenn; Delbarre, Erwan; Shah, Akshay; Sørensen, Anita Løvstad; Vigouroux, Corinne; Buendia, Brigitte & Collas, Philippe (2017). Chrom3D: Three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts. Genome Biology. ISSN 1465-6906. 18:21, s 1- 15 . doi: 10.1186/s13059-016-1146-2
- Børnich, Claus; Grytten, Ivar; Hovig, Johannes Eivind; Paulsen, Jonas; Cech, Martin & Sandve, Geir Kjetil (2016). Galaxy Portal: Interacting with the galaxy platform through mobile devices. Bioinformatics. ISSN 1367-4803. 32(11), s 1743- 1745 . doi: 10.1093/bioinformatics/btw042
- Di Stefano, Marco; Paulsen, Jonas; Lien, Tonje Gulbrandsen; Hovig, Johannes Eivind & Micheletti, Cristian (2016). Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization. Scientific Reports. ISSN 2045-2322. 6 . doi: 10.1038/srep35985
- Sekelja, Monika; Paulsen, Jonas & Collas, Philippe (2016). 4D nucleomes in single cells: What can computational modeling reveal about spatial chromatin conformation?. Genome Biology. ISSN 1465-6906. 17:54 . doi: 10.1186/s13059-016-0923-2
- Paulsen, Jonas; Gramstad, Odin & Collas, Philippe (2015). Manifold Based Optimization for Single-Cell 3D Genome Reconstruction. PloS Computational Biology. ISSN 1553-734X. 11(8) . doi: 10.1371/journal.pcbi.1004396 Full text in Research Archive.
- Håkelien, Anne-Mari; Bryne, Jan Christian; Harstad, Kristine Gjul; Lorenz, Susanne; Paulsen, Jonas; Sun, Jinchang; Mikkelsen, Tarjei S.; Myklebost, Ola & Meza, Leonardo Zepeda (2014). The regulatory landscape of osteogenic differentiation. Stem Cells. ISSN 1066-5099. 32(10), s 2780- 2793 . doi: 10.1002/stem.1759
- Paulsen, Jonas; Rødland, Einar Andreas; Holden, Lars; Holden, Marit & Hovig, Johannes Eivind (2014). A statistical model of ChIA-PET data for accurate detection of chromatin 3D interactions. Nucleic Acids Research. ISSN 0305-1048. 42(18), s e143 . doi: 10.1093/nar/gku738 Show summary
- Paulsen, Jonas; Sandve, Geir Kjetil F.; Gundersen, Sveinung; Lien, Tonje Gulbrandsen; Trengereid, Kai & Hovig, Johannes Eivind (2014). HiBrowse: Multi-purpose statistical analysis of genome-wide chromatin 3D organization. Bioinformatics. ISSN 1367-4803. 30(11), s 1620- 1622 . doi: 10.1093/bioinformatics/btu082
- Sandve, Geir Kjetil; Gundersen, Sveinung; Johansen, Morten; Glad, Ingrid Kristine; Gunathasan, Krishanthi; Holden, Lars; Holden, Marit; Liestøl, Knut; Nygård, Ståle; Nygaard, Vegard; Paulsen, Jonas; Rydbeck, Halfdan; Trengereid, Kai; Clancy, Trevor; Drabløs, Finn; Ferkingstad, Egil; Kalaš, Matúš; Lien, Tonje Gulbrandsen; Rye, Morten Beck; Frigessi, Arnoldo & Hovig, Johannes Eivind (2013). The Genomic HyperBrowser: an analysis web server for genome-scale data. Nucleic Acids Research. ISSN 0305-1048. 41(W1), s W133- W141 . doi: 10.1093/nar/gkt342 Full text in Research Archive. Show summary
- Paulsen, Jonas; Lien, Tonje Gulbrandsen; Sandve, Geir Kjetil; Holden, Lars; Borgan, Ørnulf; Glad, Ingrid Kristine & Hovig, Johannes Eivind (2013). Handling realistic assumptions in hypothesis testing of 3D co-localization of genomic elements. Nucleic Acids Research. ISSN 0305-1048. 41(10), s 5164- 5174 . doi: 10.1093/nar/gkt227 Show summary
- Nordstrand, Line Mari; Furu, Kari; Paulsen, Jonas; Rognes, Torbjørn & Klungland, Arne (2012). Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes. Nucleic Acids Research. ISSN 0305-1048. 40(21), s 10950- 10963 . doi: 10.1093/nar/gks839 Full text in Research Archive.
- Paulsen, Jonas (2014). Inferential analysis of genomic 3D organization.
- Star, Bastiaan; Nederbragt, Alexander Johan; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin; Gregers, Tone Fredsvik; Rounge, Trine Ballestad; Solbakken, Monica Hongrø; Paulsen, Jonas; Lagesen, Karin; Tooming-Klunderud, Ave; Tina, Kirubakaran G.; Espelund, Mari; Skage, Morten; Berg, Paul Ragnar; Omholt, Stig W; Stenseth, Nils Christian & Jakobsen, Kjetill Sigurd (2011). The genome of Atlantic cod reveals a unique immune system.