A report from the Chair of the Human Variome Project Gene & Disease Specific Database Advisory Council

1. SESSION VI
HVP Gene & Disease Specific Database Advisory Council
Thursday 2nd June
Report from the
Gene & Disease Specific Database Advisory Council
Peter Taschner (chair)

2. April 26, 2015
MD2015 2

3. • Share gene and disease-specific variant and phenotype data
using public databases
• Improve data interoperability to support data integration
– Standardize descriptions:
• Sequence variants: HGVS nomenclature
• Structural variants: ISCN cytogenetic nomenclature
Contact Varnomen@HGVS.org with questions and suggestions!
• Phenotypes: Human Phenotype Ontology (HPO)
Gene & Disease Specific Database Advisory Council
Recommendations

4. • Gene/Disease Specific Variant Database Quality
Parameters (HVP/GL/001-01/EN)
– Next step: implementation by databases & platforms
• Disclaimer Statements for Gene/Disease Specific
Databases (HVP/GL/002-01/EN)
• Variant Terminology and Exon Numbering
(HVP/GL/003-01/EN)
Guidelines produced by GDSDBAC

5. • WG06: Disease & Phenotype descriptions in
Gene/Disease Specific Databases (chair: Peter Robinson)
• WG08: Ethics checklist for Gene/Disease Specific
Database curators and submitters
(chair: Rosemary Ekong)
Working Groups sponsored by GDSDBAC

6. • WG02: Assigning pathogenicity to a Genetic Variant
(chair: Marc Greenblatt)
• WG03: Minimal content for Gene Variant Databases
(LSDBs)(chair: Peter Taschner) Related to WG07
• WG04: Sequence variant description committee
(chair: Johan den Dunnen)
Working Groups sponsored by ISAC

7. sequence variant nomenclature (varnomen.hgvs.org)
Leiden Open Variation Database (www.lovd.nl)
Mutalyzer sequence variant checker (mutalyzer.nl)
Sequence format: Stable reference for diagnostics
(www.lrg-sequence.org)
HVP Recommended Systems

8. Journals
mandatory submission (genotype + phenotype)
genome browsers
drawer archive
current database
mandatory submission
(genotype + phenotype)
Gene variant databases
(whole genome installation)
+ per gene views
Central repository
Diagnostic labs
( National Databases )
( Ethnic Databases )
per gene data
exome data
genome data
Research
Ideal genotype-phenotype data flow
Who checks the databases?
Who checks the journals?

9. Letters drawn up for editors of genetics/genomics journals:
• Ask inclusion of correct nomenclature use and database submission in instructions
to authors.
Letters sent by HVP ICO
HVP Genetics and Genomics Journal List:
http://www.humanvariomeproject.org/resources/genetics-and-genomics-
journals.html
GDSDBAC action

10. Call on HVP Members:
• Ensure nomenclature and database submission adequately addressed in:
– own papers,
– papers they review
– instructions to authors issued by the journals that they are involved with.
• Timeline: next 12 months
Call on ICCAC members:
• Ask national human genetics societies to address:
– Proper use of nomenclature and database submission
GDSDBAC action

11. FAIR data
Findable: data uniquely and persistently identifiable.
Others should be able to find your data.
Accessible: conditions for use clear to machines and humans.
Interoperable: machine-readable data,
terminologies, vocabularies, or ontologies commonly used in the field;
Reusable: compliant with the above,
sufficiently well described with metadata and provenance information
supporting linking or integration with other data sources, enabling proper citation.

12. Research data life cycle
http://data4lifesciences.nl/hands/handbook-for-adequate-natural-data-stewardship/

13. • Search using http://Gene_symbol.LOVD.nl
– http://TP53.lovd.nl redirects to list or TP53 database homepage
– http://USH2A.lovd.nl redirects to list
Gene variant database lookup

14. http://findis.org
Finnish Disease portal: selected data

15. Genetic testing in Amsterdam: 178 nationalities
Why share genetic data?
Genetics vs. Genomics
Reducing disease, increasing health

16. Variant assessment and classification
Share genotype and phenotype information
with gene variant databases

17. Heidi Rehm
Mark variants by level of curation
Clinical utility
Research
Genotype interpretation requires deep phenotype information

18. Capacity building
• HVP members from different countries should:
– Not re-invent the wheel, but contribute: inclusive innovation
• Adopt and translate international guidelines, standards and ontologies
• Mention problems, suggest solutions, help to implement
– Get sufficient training: follow guidelines, apply standards clinical practice
• Gene variant database curation courses
– Help to develop training and education locally
• Dutch medical geneticists: curriculum “Genetic nurse”
• Accreditation necessary
An important role for country nodes!