VarGenius-HZD allows accurate detection of rare homozygous or hemizygous deletions in targeted sequencing leveraging breadth of coverage

Abstract

AbstractMotivationHomozygous deletions (HDs) may be the cause of rare diseases and cancer and their discovery in targeted sequencing is a challenging task. Different tools have been developed to disentangle HD discovery but a sensitive caller is still lacking.ResultsWe present VarGenius-HZD, a sensitive and scalable algorithm that leverages breadth-of-coverage for the detection of rare homozygous and hemizygous single-exon deletions (HDs). To assess its effectiveness we detected both real and synthetic rare HDs in fifty exomes from the 1000 Genomes Project obtaining higher sensitivity in comparison with state-of-the-art algorithms which missed at least one event each. We then applied our tool on targeted sequencing data from patients with Inherited Retinal Dystrophies and solved five cases that still lacked a genetic diagnosis.Availability and implementationWe provide VarGenius-HZD either stand-alone or integrated within our recently developed software enabling the automated selection of samples using the internal database. Hence, it could be extremely useful for both diagnostic and research purposes. Our tool is available under GNU General Public License, version 3 at: https://github.com/frankMusacchia/VarGenius-HZDContact: francesco.musacchia@iit.itSupplementary information is available online.