1. Inferring diploid 3D chromatin structures from Hi-C data
- Author
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Alexandra Gesine Cauer, Jean-Philippe Vert, Nelle Varoquaux, William Stafford Noble, Gürkan Yardimci, Centre de Bioinformatique (CBIO), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Google Brain, Paris, Berkeley Institute for Data Science (BIDS), Department of Genome Sciences [Seattle] (GS), and University of Washington [Seattle]
- Subjects
Regulation of gene expression ,0303 health sciences ,000 Computer science, knowledge, general works ,Inference ,Computational biology ,Biology ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Data type ,Genome ,Chromatin ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Computer Science ,Homologous chromosome ,Ploidy ,ComputingMilieux_MISCELLANEOUS ,030217 neurology & neurosurgery ,X chromosome ,030304 developmental biology - 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.
- Published
- 2019