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Studying the 3D structure of the P falciparum's genome by modeling contact counts as random Negative Binomial variables Varoquaux, Nelle


The spatial and temporal organization of the 3D structure of chromosomes is thought to have an important role in genomic function, but is poorly understood. For example, there is a relative paucity of specific transcription factors, and an abundance of chromatin remodeling enzyme in the deadly human parasite P. falciparum. This points towards the involvement of global and local chromatin structure to control gene expression. Recent advances in chromosomes conformation capture (3C) technologies, initially developed to assess interactions between specific pairs of loci, allow one to simultaneously measure multiple contacts on a genome scale, paving the way for more systematic and genome-wide analysis of the 3D architecture of the genome. These new Hi-C techniques result in a genome-wide contact map, a matrix indicating the contact frequency between pairs of loci. I will present here the computational methods we developed to study the 3D organization of the parasite P. falciparum's genome using these contact maps, as well as how we uncovered the 3D structure of the parasite as a critical regulator for transcription and virulence factors in the human malaria parasite. I will discuss how appropriate modeling of contact counts as random Negative Binomial variables allowed us to build robust and accurate 3D models of the genome, as well as to perform differential analysis of the contact maps across different timepoints.

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