1. Inference of genome 3D architecture by modeling overdispersion of Hi-C data
- Author
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Nelle Varoquaux, William Stafford Noble, Jean-Philippe Vert, Univ. Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, 38000 Grenoble, France, Department of Genome Sciences [Seattle] (GS), University of Washington [Seattle], Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, Google Brain, Paris, 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), Translational microbial Evolution and Engineering (TIMC-TrEE), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Google Research [Paris], Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Varoquaux, Nelle
- Subjects
0303 health sciences ,Computer science ,[SDV]Life Sciences [q-bio] ,Negative binomial distribution ,Inference ,Function (mathematics) ,Poisson distribution ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,[SDV] Life Sciences [q-bio] ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Overdispersion ,symbols ,Poisson regression ,Multidimensional scaling ,Algorithm ,030217 neurology & neurosurgery ,030304 developmental biology ,Count data - Abstract
We address the challenge of inferring a consensus 3D model of genome architecture from Hi-C data. Existing approaches most often rely on a two step algorithm: first convert the contact counts into distances, then optimize an objective function akin to multidimensional scaling (MDS) to infer a 3D model. Other approaches use a maximum likelihood approach, modeling the contact counts between two loci as a Poisson random variable whose intensity is a decreasing function of the distance between them. However, a Poisson model of contact counts implies that the variance of the data is equal to the mean, a relationship that is often too restrictive to properly model count data.We first confirm the presence of overdispersion in several real Hi-C data sets, and we show that the overdispersion arises even in simulated data sets. We then propose a new model, called Pastis-NB, where we replace the Poisson model of contact counts by a negative binomial one, which is parametrized by a mean and a separate dispersion parameter. The dispersion parameter allows the variance to be adjusted independently from the mean, thus better modeling overdispersed data. We compare the results of Pastis-NB to those of several previously published algorithms: three MDS-based methods (ShRec3D, ChromSDE, and Pastis-MDS) and a statistical methods based on a Poisson model of the data (Pastis-PM). We show that the negative binomial inference yields more accurate structures on simulated data, and more robust structures than other models across real Hi-C replicates and across different resolutions.A Python implementation of Pastis-NB is available at https://github.com/hiclib/pastis under the BSD licenseSupplementary information is available at https://nellev.github.io/pastisnb/
- Published
- 2022