{"id":157462,"date":"2007-01-01T00:00:00","date_gmt":"2007-01-01T00:00:00","guid":{"rendered":"https:\/\/www.microsoft.com\/en-us\/research\/msr-research-item\/leveraging-hierarchical-population-structure-in-discrete-association-studies\/"},"modified":"2018-10-16T20:43:46","modified_gmt":"2018-10-17T03:43:46","slug":"leveraging-hierarchical-population-structure-in-discrete-association-studies","status":"publish","type":"msr-research-item","link":"https:\/\/www.microsoft.com\/en-us\/research\/publication\/leveraging-hierarchical-population-structure-in-discrete-association-studies\/","title":{"rendered":"Leveraging Hierarchical Population Structure in Discrete Association Studies"},"content":{"rendered":"<p>Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in <em>Arabidopsis thaliana<\/em>. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional [&hellip;]<\/p>\n","protected":false},"featured_media":0,"template":"","meta":{"msr-url-field":"","msr-podcast-episode":"","msrModifiedDate":"","msrModifiedDateEnabled":false,"ep_exclude_from_search":false,"_classifai_error":"","msr-author-ordering":null,"msr_publishername":"Public Library of Science San Francisco, USA","msr_publisher_other":"","msr_booktitle":"","msr_chapter":"","msr_edition":"PLoS One","msr_editors":"","msr_how_published":"","msr_isbn":"","msr_issue":"","msr_journal":"PLoS 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This genetic variation is the substrate for rapid within-host evolution. As our immune system learns to target the virus, the virus adapts, leading to an endless game of cat-and-mouse. 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