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

Mathieu Quinodoz; Virginie G. Peter; Nicola Bedoni; Béryl Royer Bertrand; Katarina Cisarova; Arash Salmaninejad; Neda Sepahi; Raquel Rodrigues; Mehran Piran; Majid Mojarrad; Alireza Pasdar; Ali Ghanbari Asad; Ana Berta Sousa; Luisa Coutinho Santos; Andrea Superti-Furga; Carlo Rivolta

doi:10.1038/s41467-020-20584-4

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

Mathieu Quinodoz, Virginie G. Peter, Nicola Bedoni, Béryl Royer Bertrand, Katarina Cisarova, Arash Salmaninejad, Neda Sepahi, Raquel Rodrigues, Mehran Piran, Majid Mojarrad, Alireza Pasdar, Ali Ghanbari Asad, Ana Berta Sousa, Luisa Coutinho Santos, Andrea Superti-Furga, Carlo Rivolta^*

^*Corresponding author for this work

Applied Medicine

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Article number	518
Number of pages	7
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20584-4
Publication status	Published - 22 Jan 2021

Bibliographical note

Acknowledgements
This work was supported by the Swiss National Science Foundation (grant # 176097, to C.R.) and by the PhD Fellowships in Life Science of the University of Lausanne (to M.Q.).

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Quinodoz, M., Peter, V. G., Bedoni, N., Royer Bertrand, B., Cisarova, K., Salmaninejad, A., Sepahi, N., Rodrigues, R., Piran, M., Mojarrad, M., Pasdar, A., Ghanbari Asad, A., Sousa, A. B., Coutinho Santos, L., Superti-Furga, A., & Rivolta, C. (2021). AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data. Nature Communications, 12(1), Article 518. https://doi.org/10.1038/s41467-020-20584-4

Quinodoz, M, Peter, VG, Bedoni, N, Royer Bertrand, B, Cisarova, K, Salmaninejad, A, Sepahi, N, Rodrigues, R, Piran, M, Mojarrad, M, Pasdar, A, Ghanbari Asad, A, Sousa, AB, Coutinho Santos, L, Superti-Furga, A & Rivolta, C 2021, 'AutoMap is a high performance homozygosity mapping tool using next-generation sequencing data', Nature Communications, vol. 12, no. 1, 518. https://doi.org/10.1038/s41467-020-20584-4

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abstract = "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.",

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AU - Superti-Furga, Andrea

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N2 - 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.

AB - 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.

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

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