Sanger validation of WGS variants
Abstract With the development of next-generation sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement, it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is th...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-87814-x |
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| author | Arina Kopernik Mariia Sayganova Gaukhar Zobkova Natalia Doroschuk Anna Smirnova Daria Molodtsova-Zolotukhina Olesya Sagaydak Oxana Ryzhkova Sergey Kutsev Olga Groznova Lyusya Melikyan Elizaveta Bondarchuk Mary Woroncow Eugene Albert Viktor Bogdanov Pavel Volchkov |
| author_facet | Arina Kopernik Mariia Sayganova Gaukhar Zobkova Natalia Doroschuk Anna Smirnova Daria Molodtsova-Zolotukhina Olesya Sagaydak Oxana Ryzhkova Sergey Kutsev Olga Groznova Lyusya Melikyan Elizaveta Bondarchuk Mary Woroncow Eugene Albert Viktor Bogdanov Pavel Volchkov |
| author_sort | Arina Kopernik |
| collection | DOAJ |
| description | Abstract With the development of next-generation sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement, it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is that one could define the quality thresholds for “high quality” variants which do not require orthogonal validation. Despite that, no works to date report the concordance between variants from whole genome sequencing and their gold-standard Sanger validation. In this study we analyzed the concordance for 1756 WGS variants in order to establish the appropriate thresholds for high-quality variants filtering. Resulting thresholds allowed us to drastically reduce the number of variants which require validation, to 4.8% and 1.2% of the initial set for caller-agnostic (DP, AF) and caller-dependent (QUAL) thresholds, respectively. |
| format | Article |
| id | doaj-art-b8cd4a5e26334cecb0231753a7863959 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b8cd4a5e26334cecb0231753a78639592025-02-02T12:18:42ZengNature PortfolioScientific Reports2045-23222025-01-011511610.1038/s41598-025-87814-xSanger validation of WGS variantsArina Kopernik0Mariia Sayganova1Gaukhar Zobkova2Natalia Doroschuk3Anna Smirnova4Daria Molodtsova-Zolotukhina5Olesya Sagaydak6Oxana Ryzhkova7Sergey Kutsev8Olga Groznova9Lyusya Melikyan10Elizaveta Bondarchuk11Mary Woroncow12Eugene Albert13Viktor Bogdanov14Pavel Volchkov15Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesEvogen LLCEvogen LLCEvogen LLCFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesEvogen LLCResearch Centre for Medical GeneticsResearch Centre for Medical GeneticsVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery on the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian FederationVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery on the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian FederationVeltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery on the Pirogov Russian National Research Medical University of the Ministry of Health of the Russian FederationLomonosov Moscow State UniversityFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesFederal Research Center for Innovator and Emerging Biomedical and Pharmaceutical TechnologiesAbstract With the development of next-generation sequencing (NGS) technologies it became possible to simultaneously analyze millions of variants. Despite the quality improvement, it is generally still required to confirm the variants before reporting. However, in recent years the dominant idea is that one could define the quality thresholds for “high quality” variants which do not require orthogonal validation. Despite that, no works to date report the concordance between variants from whole genome sequencing and their gold-standard Sanger validation. In this study we analyzed the concordance for 1756 WGS variants in order to establish the appropriate thresholds for high-quality variants filtering. Resulting thresholds allowed us to drastically reduce the number of variants which require validation, to 4.8% and 1.2% of the initial set for caller-agnostic (DP, AF) and caller-dependent (QUAL) thresholds, respectively.https://doi.org/10.1038/s41598-025-87814-x |
| spellingShingle | Arina Kopernik Mariia Sayganova Gaukhar Zobkova Natalia Doroschuk Anna Smirnova Daria Molodtsova-Zolotukhina Olesya Sagaydak Oxana Ryzhkova Sergey Kutsev Olga Groznova Lyusya Melikyan Elizaveta Bondarchuk Mary Woroncow Eugene Albert Viktor Bogdanov Pavel Volchkov Sanger validation of WGS variants Scientific Reports |
| title | Sanger validation of WGS variants |
| title_full | Sanger validation of WGS variants |
| title_fullStr | Sanger validation of WGS variants |
| title_full_unstemmed | Sanger validation of WGS variants |
| title_short | Sanger validation of WGS variants |
| title_sort | sanger validation of wgs variants |
| url | https://doi.org/10.1038/s41598-025-87814-x |
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