Phylogenomic reconstruction of spp. captured directly from clinical samples reveals extensive genetic diversity.

is a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twenty species infect humans, of which and are the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnose . Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understand global population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ~92% of the genome of . CES-Seq is sensitive and successfully sequenced genomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species of directly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.