Mapping the drivers of within-host pathogen evolution using massive data sets
9 July 2019
Palmer DS, Turner I, Fidler S, Frater J, Goedhals D, Goulder P, Huang KG, Oxenius A, Phillips R, Shapiro R, Vuuren CV, McLean AR, McVean G
Nature Communications (2019) 10(3017):1-14
Differences among hosts, resulting from genetic variation in the immune system or heterogeneity in drug treatment, can impact within-host pathogen evolution. Genetic association studies can potentially identify such interactions. However, extensive and correlated genetic population structure in hosts and pathogens presents a substantial risk of confounding analyses. Moreover, the multiple testing burden of interaction scanning can potentially limit power. We present a Bayesian approach for detecting host influences on pathogen evolution that exploits vast existing data sets of pathogen diversity to improve power and control for stratification. The approach models key processes, including recombination and selection, and identifies regions of the pathogen genome affected by host factors. Our simulations and empirical analysis of drug-induced selection on the HIV-1 genome show that the method recovers known associations and has superior precision-recall characteristics compared to other approaches. We build a high-resolution map of HLA-induced selection in the HIV-1 genome, identifying novel epitope-allele combinations.
Health data research
Health Data Science is a discipline that combines maths, statistics and technology to study different types of health problems using data. It provides the tools to manage and analyse very large...
Health Data Research UK (HDR UK) Oxford
Director Professor Martin Landray, Professor of Medicine & Epidemiology and Deputy Director, Big Data Institute, University of Oxford Associate Director Professor Gil McVean, Professor of...
Professor Gilean McVean
Professor of Statistical Genetics, Director of the Big Data Institute at University of Oxford
Gil McVean is Professor of Statistical Genetics at the University of Oxford and Director of Oxford’s Big Data Institute, BDI, within the Li Ka Shing Centre for Health Information and Discovery...