Bioinformatics Seminars

Bioinformatics Seminar

Time: 10:45am Tuesdays.
Level 7 Seminar Room 2, WEHI1

13 March 2018

Identifying Positive Selection Associated with Antimalarial Drug Resistance in Plasmodium falciparum using Identity-By-Descent Analysis

Lyndal Henden
WEHI Bioinformatics

Drug resistance in microorganisms is a global health crisis and identifying the mechanisms underlying such resistance is crucial in advancing disease control and elimination efforts. Genes associated with resistance experience selective pressures, creating strong genetic signals in the microorganism's genome. Here we present a novel method for identifying loci under recent positive selection in microorganisms using identity by descent analysis. We perform simulation studies to demonstrate the performance of our proposed statistic in detecting complex patterns of positive selection and apply our statistic to global P. falciparum data of more than 2,000 isolates. In doing so we are able to identify many well-known signals associated with antimalarial drug resistance as well as several new loci suspected of being associated with resistance. Identity by descent analysis also allows us to explore population structure through relatedness networks, providing clues as to the number of haplotypes contributing to a selection signal and the distribution of these signals within and between countries. Furthermore, we are able to determine whether a haplotype conferring drug resistance has arisen independently between geographic locations or whether it has spread from other locations

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