The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool
Abstract Background Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massiv...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-02-01
|
| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12859-018-2056-y |
| _version_ | 1818994854378602496 |
|---|---|
| author | Steven Flygare Edgar Javier Hernandez Lon Phan Barry Moore Man Li Anthony Fejes Hao Hu Karen Eilbeck Chad Huff Lynn Jorde Martin G. Reese Mark Yandell |
| author_facet | Steven Flygare Edgar Javier Hernandez Lon Phan Barry Moore Man Li Anthony Fejes Hao Hu Karen Eilbeck Chad Huff Lynn Jorde Martin G. Reese Mark Yandell |
| author_sort | Steven Flygare |
| collection | DOAJ |
| description | Abstract Background Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massive public variant repositories such as dbSNP and gnomAD. In response, we have developed VVP, the VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant repositories and genome collections, and its outputs are designed to simplify clinical interpretation of variants of uncertain significance. Results We show that scoring the entire contents of dbSNP (> 155 million variants) requires only 95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be processed in less than 5 min. We also demonstrate that VVP can score variants anywhere in the genome, regardless of type, effect, or location. It does so by integrating sequence conservation, the type of sequence change, allele frequencies, variant burden, and zygosity. Finally, we also show that VVP scores are consistently accurate, and easily interpreted, traits not shared by many commonly used tools such as SIFT and CADD. Conclusions VVP provides rapid and scalable means to prioritize any sequence variant, anywhere in the genome, and its scores are designed to facilitate variant interpretation using ACMG and NHS guidelines. These traits make it well suited for operation on very large collections of WGS sequences. |
| first_indexed | 2024-12-20T21:04:34Z |
| format | Article |
| id | doaj.art-18cbbe88691342b6b8476a5ae673f572 |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-20T21:04:34Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-18cbbe88691342b6b8476a5ae673f5722022-12-21T19:26:38ZengBMCBMC Bioinformatics1471-21052018-02-0119111310.1186/s12859-018-2056-yThe VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization toolSteven Flygare0Edgar Javier Hernandez1Lon Phan2Barry Moore3Man Li4Anthony Fejes5Hao Hu6Karen Eilbeck7Chad Huff8Lynn Jorde9Martin G. Reese10Mark Yandell11Department of Human Genetics, University of UtahDepartment of Human Genetics, University of UtahNational Center for Biotechnology InformationDepartment of Human Genetics, University of UtahDepartment of Human Genetics, University of UtahFabric GenomicsDepartment of Epidemiology, M.D. Anderson Cancer CenterUSTAR Center for Genetic DiscoveryDepartment of Epidemiology, M.D. Anderson Cancer CenterDepartment of Human Genetics, University of UtahFabric GenomicsDepartment of Human Genetics, University of UtahAbstract Background Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massive public variant repositories such as dbSNP and gnomAD. In response, we have developed VVP, the VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant repositories and genome collections, and its outputs are designed to simplify clinical interpretation of variants of uncertain significance. Results We show that scoring the entire contents of dbSNP (> 155 million variants) requires only 95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be processed in less than 5 min. We also demonstrate that VVP can score variants anywhere in the genome, regardless of type, effect, or location. It does so by integrating sequence conservation, the type of sequence change, allele frequencies, variant burden, and zygosity. Finally, we also show that VVP scores are consistently accurate, and easily interpreted, traits not shared by many commonly used tools such as SIFT and CADD. Conclusions VVP provides rapid and scalable means to prioritize any sequence variant, anywhere in the genome, and its scores are designed to facilitate variant interpretation using ACMG and NHS guidelines. These traits make it well suited for operation on very large collections of WGS sequences.http://link.springer.com/article/10.1186/s12859-018-2056-yVariant prioritizationGenomicsHuman genomeVariants of uncertain significance |
| spellingShingle | Steven Flygare Edgar Javier Hernandez Lon Phan Barry Moore Man Li Anthony Fejes Hao Hu Karen Eilbeck Chad Huff Lynn Jorde Martin G. Reese Mark Yandell The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool BMC Bioinformatics Variant prioritization Genomics Human genome Variants of uncertain significance |
| title | The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool |
| title_full | The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool |
| title_fullStr | The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool |
| title_full_unstemmed | The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool |
| title_short | The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool |
| title_sort | vaast variant prioritizer vvp ultrafast easy to use whole genome variant prioritization tool |
| topic | Variant prioritization Genomics Human genome Variants of uncertain significance |
| url | http://link.springer.com/article/10.1186/s12859-018-2056-y |
| work_keys_str_mv | AT stevenflygare thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT edgarjavierhernandez thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT lonphan thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT barrymoore thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT manli thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT anthonyfejes thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT haohu thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT kareneilbeck thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT chadhuff thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT lynnjorde thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT martingreese thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT markyandell thevaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT stevenflygare vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT edgarjavierhernandez vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT lonphan vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT barrymoore vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT manli vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT anthonyfejes vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT haohu vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT kareneilbeck vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT chadhuff vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT lynnjorde vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT martingreese vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool AT markyandell vaastvariantprioritizervvpultrafasteasytousewholegenomevariantprioritizationtool |