AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data

• Published in: Nature communications Vol. 12; no. 1; p. 518
• Main Authors: Quinodoz, Mathieu, Peter, Virginie G, Bedoni, Nicola, Royer Bertrand, Béryl, Cisarova, Katarina, Salmaninejad, Arash, Sepahi, Neda, Rodrigues, Raquel, Piran, Mehran, Mojarrad, Majid, Pasdar, Alireza, Ghanbari Asad, Ali, Fonseca Vieira Álvares Sousa Ferrand Almeida, Ana Berta, Santos, Maria Luisa, Superti-Furga, Andrea, Rivolta, Carlo
• Format: Journal Article
• Language: English
• Published: London Springer Nature 22-01-2021; Nature Publishing Group UK; Nature Publishing Group; Nature Portfolio
• Subjects: 45/23; 45/61; 631/1647/48; 631/208/1397; 631/208/212; 631/208/514/2254; Chromosome Mapping - methods; Computational Biology - methods; Deoxyribonucleic acid; Diagnosis; DNA; Gene mapping; Gene sequencing; Genetic Predisposition to Disease - genetics; Genetics; Genome, Human - genetics; Genomes; Genotype; Genotypes; High-Throughput Nucleotide Sequencing - methods; Homozygosity; Homozygote; Humanities and Social Sciences; Humans; Internet; Mapping; Medical research; Microsatellites; multidisciplinary; Mutation; Next-generation sequencing; Polymorphism, Single Nucleotide; Reproducibility of Results; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Software; Whole Exome Sequencing - methods; Whole genome sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20584-4

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Homozygosity mapping is a powerful method for identifying mutations in patients with recessive conditions, especially in consanguineous families or isolated populations. Historically, it has been used in conjunction with genotypes from highly polymorphic markers, such as DNA microsatellites or common SNPs. Traditional software performs rather poorly with data from Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS), which are now extensively used in medical genetics. We develop AutoMap, a tool that is both web-based or downloadable, to allow performing homozygosity mapping directly on VCF (Variant Call Format) calls from WES or WGS projects. Following a training step on WES data from 26 consanguineous families and a validation procedure on a matched cohort, our method shows higher overall performances when compared with eight existing tools. Most importantly, when tested on real cases with negative molecular diagnosis from an internal set, AutoMap detects three gene-disease and multiple variant-disease associations that were previously unrecognized, projecting clear benefits for both molecular diagnosis and research activities in medical genetics.