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Inferring diploid 3D chromatin structures from Hi-C data

View ORCID ProfileAlexandra Gesine Cauer, Gürkan Yardimci, Jean-Philippe Vert, View ORCID ProfileNelle Varoquaux, William Stafford Noble
doi: https://doi.org/10.1101/644294
Alexandra Gesine Cauer
1Department of Genome Sciences, University of Washington,
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  • For correspondence: gesine@uw.edu
Gürkan Yardimci
2Department of Genome Sciences, University of Washington,
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  • For correspondence: gurkan@uw.edu
Jean-Philippe Vert
3Google Brain, Paris
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  • For correspondence: jpvert@google.com
Nelle Varoquaux
4Department of Statistics, UC Berkeley,
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  • For correspondence: nelle.varoquaux@gmail.com
William Stafford Noble
5Department of Genome Sciences, University of Washington, Paul G. Allen School of Computer Science and Engineering, University of Washington
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Abstract

The 3D organization of the genome plays a key role in many cellular processes, such as gene regulation, differentiation, and replication. Assays like Hi-C measure DNA-DNA contacts in a high-throughput fashion, and inferring accurate 3D models of chromosomes can yield insights hidden in the raw data. For example, structural inference can account for noise in the data, disambiguate the distinct structures of homologous chromosomes, orient genomic regions relative to nuclear landmarks, and serve as a framework for integrating other data types. Although many methods exist to infer the 3D structure of haploid genomes, inferring a diploid structure from Hi-C data is still an open problem. Indeed, the diploid case is very challenging, because Hi-C data typically does not distinguish between homologous chromosomes. We propose a method to infer 3D diploid genomes from Hi-C data. We demonstrate the accuarcy of the method on simulated data, and we also use the method to infer 3D structures for mouse chromosome X, confirming that the active homolog exhibits a bipartite structure, whereas the active homolog does not.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 21, 2019.
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Inferring diploid 3D chromatin structures from Hi-C data
Alexandra Gesine Cauer, Gürkan Yardimci, Jean-Philippe Vert, Nelle Varoquaux, William Stafford Noble
bioRxiv 644294; doi: https://doi.org/10.1101/644294
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Inferring diploid 3D chromatin structures from Hi-C data
Alexandra Gesine Cauer, Gürkan Yardimci, Jean-Philippe Vert, Nelle Varoquaux, William Stafford Noble
bioRxiv 644294; doi: https://doi.org/10.1101/644294

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