Abstract
A critical element in sharing of genomic information is the use of standardized terms. However, DNA variants are described in many publications using various non-standardized or legacy-based naming system that are familiar within select communities (e.g., oncology, immunology, or pharmacogenetics) but may not facilitate data exchange. This may seem trivial, but it is an unfortunate fact that a lack of adherence to the correct naming of variants in clinical journals has contributed to lengthy diagnostic journeys and the inability of many patients to receive any diagnosis, particularly in rare disease diagnostics where there is a dire need to expand the evidence pool. It is our duty to do everything that we can to reduce the odyssey, enable diagnoses and improve patient outcomes. A crucial part of the diagnostic process requires clinicians to search journals for relevant evidence. However, because of poor variant reporting, and a lack of standards-driven Open Source validation software, all too often clinicians are unable to locate evidence even if it has been published. Additionally, poor reporting also prevents clinical databases, e.g., ClinVar utilizing LitVar2 (https://www.ncbi.nlm.nih.gov/research/litvar2/) and Leiden Open Variation Database (LOVD) from identifying literature and associating it with their records.
VariantValidator (https://variantvalidator.org/) is an Open Source variant validation tool used by researchers and clinicians to ensure the accuracy of the sequence‐level variation descriptions they are reporting. VariantValidator standardises variant descriptions against the Human Genome Variation Society (HGVS) variant nomenclature, by providing a user friendly Graphical and Programmatic interfaces and to guide users through the intricacies of the HGVS nomenclature. In a single validation HGVS formatted descriptions are generated and displayed in the context of all relevant reference sequences (genome, transcript, protein) and are also automatically projected between genome builds GRCh37 and GRCh38. Additionally, VariantValidator automatically inter-converts between the HGVS and Variant Call Format (VCF) description formats, again displaying lift-over between genome builds. VariantValidator has been used extensively to standardise the naming of genetic variants in clinical reports, literature, and databases. It is contributing to the following key clinical areas:
· Training: VariantValidator is integrated into, amongst other things, NHS scientist training delivered at the University of Manchester via reusable online material that could also be repurposed to educate an international audience.
· Interoperability and standards: VariantValidator is built to produce standards-driven and interoperable variant descriptions and is endorsed by the Human Genome Organisation (HUGO) and quality standards agencies in the USA and Europe.
. Professional practice: VariantValidator is embedded in decision making pipelines in diagnostic labs including the NHS North West and South East Genomic Laboratory Hubs, several labs in the US and Europe (as the gateway software of Leiden Open Variation Database (LOVD) Pro v3.5 onwards)
Backed by HUGO, VariantValidator is being built into editorial management software to ensure that all genetic variants reported in published papers and reviews are precisely named. VariantValidator is serving a community of editors and authors who are working hard to make clinical data more findable, and over time will make genetic diagnoses faster and safer. The VariantValidator team is working with two of the world’s leading variant databases, Clinvar and LOVD, to standardise their sequence variation descriptions. We are also working to support a HUGO ACMG joint professional standard aiming to standardise the reporting of sequence variation, and the clinical classification process in biomedical journals and databases, ensuring the precise flow of data from clinical report, to journal, to database. The findability and interoperability between these services we are working towards will make clinical genetics data easier to discover and will, in time, help to reduce the diagnostic odyssey.
VariantValidator (https://variantvalidator.org/) is an Open Source variant validation tool used by researchers and clinicians to ensure the accuracy of the sequence‐level variation descriptions they are reporting. VariantValidator standardises variant descriptions against the Human Genome Variation Society (HGVS) variant nomenclature, by providing a user friendly Graphical and Programmatic interfaces and to guide users through the intricacies of the HGVS nomenclature. In a single validation HGVS formatted descriptions are generated and displayed in the context of all relevant reference sequences (genome, transcript, protein) and are also automatically projected between genome builds GRCh37 and GRCh38. Additionally, VariantValidator automatically inter-converts between the HGVS and Variant Call Format (VCF) description formats, again displaying lift-over between genome builds. VariantValidator has been used extensively to standardise the naming of genetic variants in clinical reports, literature, and databases. It is contributing to the following key clinical areas:
· Training: VariantValidator is integrated into, amongst other things, NHS scientist training delivered at the University of Manchester via reusable online material that could also be repurposed to educate an international audience.
· Interoperability and standards: VariantValidator is built to produce standards-driven and interoperable variant descriptions and is endorsed by the Human Genome Organisation (HUGO) and quality standards agencies in the USA and Europe.
. Professional practice: VariantValidator is embedded in decision making pipelines in diagnostic labs including the NHS North West and South East Genomic Laboratory Hubs, several labs in the US and Europe (as the gateway software of Leiden Open Variation Database (LOVD) Pro v3.5 onwards)
Backed by HUGO, VariantValidator is being built into editorial management software to ensure that all genetic variants reported in published papers and reviews are precisely named. VariantValidator is serving a community of editors and authors who are working hard to make clinical data more findable, and over time will make genetic diagnoses faster and safer. The VariantValidator team is working with two of the world’s leading variant databases, Clinvar and LOVD, to standardise their sequence variation descriptions. We are also working to support a HUGO ACMG joint professional standard aiming to standardise the reporting of sequence variation, and the clinical classification process in biomedical journals and databases, ensuring the precise flow of data from clinical report, to journal, to database. The findability and interoperability between these services we are working towards will make clinical genetics data easier to discover and will, in time, help to reduce the diagnostic odyssey.
Original language | English |
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Publication status | Published - Oct 2023 |
Event | Manchester Dysmorphology Conference - Hilton Hotel, Manchester, United Kingdom Duration: 16 Oct 2023 → 18 Oct 2023 https://www.mrcc.org.uk/events/conferences/manchester-dysmorphology-conference-2023/ |
Conference
Conference | Manchester Dysmorphology Conference |
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Country/Territory | United Kingdom |
City | Manchester |
Period | 16/10/23 → 18/10/23 |
Internet address |