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Musacchia F, Karali M, Torella A, et al. VarGenius-HZD Allows Accurate Detection of Rare Homozygous or Hemizygous Deletions in Targeted Sequencing Leveraging Breadth of Coverage. Genes (Basel). 2021;12(12)doi: 10.3390/genes12121979.
Musacchia, F., Karali, M., Torella, A., Laurie, S., Policastro, V., Pizzo, M., Beltran, S., Casari, G., Nigro, V., & Banfi, S. (2021). VarGenius-HZD Allows Accurate Detection of Rare Homozygous or Hemizygous Deletions in Targeted Sequencing Leveraging Breadth of Coverage. Genes, 12(12), . https://doi.org/10.3390/genes12121979
Musacchia, Francesco, et al. "VarGenius-HZD Allows Accurate Detection of Rare Homozygous or Hemizygous Deletions in Targeted Sequencing Leveraging Breadth of Coverage." Genes vol. 12,12 (2021). doi: https://doi.org/10.3390/genes12121979
Musacchia F, Karali M, Torella A, Laurie S, Policastro V, Pizzo M, Beltran S, Casari G, Nigro V, Banfi 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). doi: 10.3390/genes12121979. PMID: 34946927.
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Genes (Basel). 2021 Dec 13;12(12). doi: 10.3390/genes12121979.

VarGenius-HZD Allows Accurate Detection of Rare Homozygous or Hemizygous Deletions in Targeted Sequencing Leveraging Breadth of Coverage.

Genes

Francesco Musacchia, Marianthi Karali, Annalaura Torella, Steve Laurie, Valeria Policastro, Mariateresa Pizzo, Sergi Beltran, Giorgio Casari, Vincenzo Nigro, Sandro Banfi

Affiliations

  1. Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy.
  2. Center for Human Technologies, Istituto Italiano di Tecnologia, 16163 Genova, Italy.
  3. Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', 80138 Naples, Italy.
  4. Medical Genetics, Department of Precision Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', 80138 Naples, Italy.
  5. CNAG-CRG, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003 Barcelona, Spain.
  6. Institute for Applied Mathematics "Mauro Picone" (IAC), National Research Council, 80131 Naples, Italy.
  7. Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Università degli Studi della Campania 'Luigi Vanvitelli', 81100 Caserta, Italy.
  8. Universitat Pompeu Fabra (UPF), 08017 Barcelona, Spain.
  9. Department of Genetics, Microbiology and Statistics, Universitat de Barcelona (UB), 08028 Barcelona, Spain.
  10. Neurogenomics Unit, Center for Genomics, Bioinformatics and Biostatistics, San Raffaele Scientific Institute, 20132 Milan, Italy.

PMID: 34946927 DOI: 10.3390/genes12121979

Abstract

Homozygous 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.

Keywords: copy-number variation; homozygous deletion; rare diseases

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