SESSION VIHVP Gene & Disease Specific Database Advisory Council

Thursday 2nd June

Report from the Gene & Disease Specific Database Advisory CouncilPeter Taschner (chair)

April 26, 2015MD2015 2

• 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

• 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

• 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

• 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

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

Journals

mandatory submission (genotype + phenotype)

genome browsers

drawer archivecurrent database

mandatory submission(genotype + phenotype)

Gene variant databases(whole genome installation)

+ per gene views

Central repository

Diagnostic labs

( National Databases )( Ethnic Databases )

per gene dataexome data

genome data

Research

Ideal genotype-phenotype data flow

Who checks the databases?

Who checks the journals?

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

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

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.

Research data life cycle

http://data4lifesciences.nl/hands/handbook-for-adequate-natural-data-stewardship/

• 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

http://findis.org

Finnish Disease portal: selected data

Genetic testing in Amsterdam: 178 nationalities

Why share genetic data?

Genetics vs. GenomicsReducing disease, increasing health

Variant assessment and classification

Share genotype and phenotype informationwith gene variant databases

Heidi Rehm

Mark variants by level of curation

Clinical utility

Research

Genotype interpretation requires deep phenotype information

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!