https://www.walmart.com/ip/Popsicle-Rainbow-Big-Stick-3-5-oz/198225061 POPSICLE- a software suite to determine population structure and Ancestral Determinants of Phenotypes using Whole Genome Sequencing data niaidlogo





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POPSICLEPipeline

The advent of new sequencing technologies has provided access to genome-wide markers which may be evaluated for their association with the observed phenotypes. Recent studies have leveraged these technologies and sequenced hundreds and sometimes thousands of strains to improve accuracy of genotype-phenotype predictions. Sequencing of thousands of strains is not practical for many research groups which argues for formulation of new strategies that improve predictability using a fraction of cost and by using only a few samples. We introduce here a novel computational algorithm called POPSICLE that exploits the local genetic variations to infer blocks of shared ancestries to construct complex evolutionary relationships. These evolutionary relationships are subsequently visualized using chromosome painting, as admixtures and as clades to acquire general as well as specific ancestral relationships within populations. In addition, POPSICLE evaluates the ancestral blocks for their association with phenotypes thereby bridging two powerful methodologies from population genetics and genome-wide association studies. In comparison to the existing tools, POPSICLE offers substantial improvements in terms of accuracy, speed and automation. We evaluated POPSICLE’s ability to find genetic determinants of P. falciparum’s resistance to Artemisinin using 57 out of 1,612 strains that were used in the original study. POPSICLE was able to accurately infer key genes implicated in the original study and found new gene families that were previously implicated in resistance to Artemisinin. We further extended this analysis to find shared ancestries among closely related P. falciparum, P. reichenowi and P. gaboni species from Laverania subgenus of Plasmodium. POPSICLE was able to accurately infer the population structure of Laverania subgenus and detected strains which are coinfections involving P. falciparum and P. gaboni. 


CITATION: Jahangheer S. Shaik, Asis Khan and Michael E. Grigg, "POPSICLE: A Software Suite to Study Population Structure and Ancestral Determinants of Phenotypes using Whole genome Sequencing Data", submitted to PLoS special edition