DMuDB: a shared mutation repository for UK diagnostic labs Andrew Devereau, Ed Burke

Aim Sharing – To act as a central repository for mutation data generated by UK diagnostic laboratories to support future diagnoses Publishing – To support the wider publication of this data by working in collaboration with established projects

Progress Initial data sets have been collected – NF1, NF2, RPGR & CFTR which have aided in final database development. Community standards adopted. Steering group formed to provide policy decisions. Software to aid submission and data presentation developed.

DMuDB Demonstration

XML Import Tool Spreadsheet containing diagnostic lab data Referrals created in DMuDB XML translation

Graphical Display Graphics Generation Secure Interface NGRL Server Diagnostic Lab User DMuDBLOVD LOVD User NF1 data from DMuDB DMD data from (LOVD)

Current & Future Priorities Encourage submission from diagnostic labs in the UK. Further develop the graphics to allow the display of data from other databases. Allow display of overview data for non- registered users, access for non-diagnostic lab users. Formalise a route to get the data out of DMuDB and into the public domain.

Issues (1) – Reference Sequences Diagnostic labs use in-house reference sequences. Sequences are formatted rather than marked-up. Translation of variant information between reference sequences is impractical.

Issues (2) - Nomenclature HGVS nomenclature adopted, but this alone is not sufficient. Nomenclature is not machine readable, therefore alternative methods for exchanging and storing variants are necessary. Some problems exist within labs in interpreting guidelines. Updating database to reflect changes in nomenclature is time consuming.

Issues (3) – Controlled Vocabulary Necessary for data exchange Guidelines exist – but these are not formalised Interoperability with future NHS systems might require vocabularies to be changed later

Issues (4) – Data Export Confidentiality must be maintained. Several other databases have been investigated for suitability – HGMD, LOVD, Waystation, Human Mutation. Importing and exporting data requires a minimum set of data. Original submitters need to be recognised.

Summary A repository developed to support mutation sharing in UK labs Bulk submission and graphical display developed Issues include standardisation of reference sequences, nomenclature, vocabulary and data formats for export and import A route for publication is needed

Acknowledgements Graham Taylor David Gokhale DMuDB Steering Group Ian BamseyCertus Technology Associates Rob PumpheryCertus Technology Associates Ning ZhangUniversity of Manchester UK Department of Health