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Towards a genome-scale coevolutionary analysis

Abstract : Advances in sequencing technologies have revolutionized the life sciences. The explosion of genomic sequence data has prompted the development of a wide variety of methods, at the interface between bioinformatics, machine learning, and physics, which aim at gaining a deeper understanding of biological systems from such data.Pairwise coevolutionary methods, in particular Direct Coupling Analysis (DCA), can extract a multitude of information from sequence data alone, such as structural contacts or phenotypic effects of amino-acid substitutions in proteins. While they have been mainly applied to a number of single exemplary proteins, it is now time for a broader application at the level of the whole genome. In this thesis, we build upon and extend these models to address biological questions at the genome scale. In a first project, we investigate the protein-protein interaction network by combining coevolutionary signals at multiple but interconnected scales. In a subsequent project, we discuss the possibility of including complementary information to sequences, such as typical patterns of contacts, to improve the inter-protein contact prediction. Finally, through an extensive genome-wide study of E. coli strains, we show how the machinery of DCA can be used to investigate the fitness landscape properties at the local and global scales.
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Submitted on : Wednesday, August 5, 2020 - 11:37:07 AM
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  • HAL Id : tel-02912097, version 1

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Giancarlo Croce. Towards a genome-scale coevolutionary analysis. Bioinformatics [q-bio.QM]. Sorbonne Université, 2019. English. ⟨tel-02912097⟩

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