Musacchia, FrancescoKarali, MarianthiTorella, AnnalauraLaurie, Steven, 1973-Policastro, ValeriaPizzo, MariateresaBeltran, SergiCasari, GiorgioNigro, VincenzoBanfi, Sandro2022-03-242022-03-242021Musacchia F, Karali M, Torella A, Laurie S, Policastro V, Pizzo M, Beltran S. VarGenius-HZD allows accurate detection of rare homozygous or hemizygous deletions in targeted sequencing leveraging breadth of coverage. Genes (Basel). 2021 Dec 13;12(12):1979. DOI: 10.3390/genes121219792073-4425http://hdl.handle.net/10230/52766Homozygous 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. We 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 that each missed at least one event. 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. We 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.application/pdfeng© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).info:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/genes12121979Copy-number variationHomozygous deletionRare diseasesinfo:eu-repo/semantics/openAccess