GEN2PHEN SUMMARY PROGRESS REPORT
Period: January-April 2009
INTRODUCTION
The GEN2PHEN project continues to enjoy widespread recognition and a rapid rate of progress. Consequently, the program of work is now well ahead of schedule on many fronts, and deeply connected, via high-level collaborations, to many other leading projects (e.g.,
CASIMIR, ENGAGE, P3G, HVP, InSiGHT, BBMRI, ELIXIR).
Some of the most notable achievements in the January-April 2009 period include: a) All scheduled Deliverables completed, submitted, and accepted, and first year scientific and financial reporting completed b) Extensive community discussion (workshop & website) regarding new ideas for ‘digital IDs for researchers’, thereby bringing this issue to the attention of all major funders and G2P researchers. Collaborations with leading informatics groups towards real-world implementations are now being discussed c) Good progress on key standards: publication of the PAGE-OM data model, advanced model for phenotype data, work towards robust phenotype ontologies, finalisation efforts on the LRG reference models for disease genes, ethics assessment to provide standardised basis for data exchange d) Considerable progress on creating databases (~800) for gene-disease association study data and locus-specific disease mutations, plus many partnerships with the community towards running these databases and populating them with carefully curated data e) Enhanced connectivity between LSDBs, DiseaseCard, Ensembl, & Swiss-Prot f) Extensive community interaction and dissemination work
WP1: SCIENTIFIC COORDINATION

Held General Assembly Meeting #3 (GAM3) and Steering Committee Meeting #5 (SCM5), 18-
20 Febraury in Leicester, UK.

Scientific Advisory Board report with assessment of 1 st
year progress compiled and delivered to the Commission. Follow-on discussions on 'clinical-GEN2PHEN’.

Preparation, test and launch of an ethics survey questionnaire

Completed 1 st
year Project Pilot.
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
Completed and submitted Deliverables:
- D1.2: “Initial Report from Project Assessment Pilot”
- D1.3: “Report on General Ethical Issues in G2P Database Work”
- D2.1: “Workshop to Review the G2P Database Field and Current Data Models”
- D3.2: “Development of High-Level Domain Model Version-1”
- D8.1: “Procedures to Establish Internal Training Needs”
- D9.1: “GEN2PHEN Communication Plan”
WP2: DOMAIN ANALYSIS AND COMMUNITY RELATIONS

Attended ontology workshop on “Anatomical Basis of Disease”, organised by the Virtual
Physiological Human (VPH) community.

Launched surveys on i) genome browsers, and ii) browsers used by clinical groups
WP3: STANDARD DATA MODELS AND TERMINOLOGIES

Held workshop on data exchange models for LSDBs, Diagnostic Labs, and GWAS data

Ontology development work:
- ontology session planned at P3G meeting in Brussels (March 2009)
- discussions with FMA on new features useful for genetic disorder description
- preliminary evaluation of DMuDB controlled vocabulary
- recommended improvements to 'Sequence Ontology' terms related to G2P field
- discussion with CIMR on G2P ontology use cases in autoimmune diseases
- released an EFO branch with integrated metabolic syndrome vocabulary (for ENGAGE)
- submitted NGRL testing technologies vocabulary to OBI and EFO

Organised a Phenotype Workshop, and prepared a summary report

Set up an SVN location for iterative object model development.

Established cooperation with DataShaper and PhenX to gather ontology use cases.

Worked with LSDBs curators towards an SOA document on data exchange formats

Worked towards a G2P data exchange format

Created v1 XML schema & documentation based on the GEN2PHEN core LSDB data model
WP4: GENETICS G2P DATABASES

Launched many new LSDBs (LOVD and UMD platforms)

Restructured existing HNPCC LSDBs into LOVD platform, with InSiGHT Consortium.

Collaborations agreed to build LSDBs for genes involved in Congenital Muscular Dystrophies.

Planned a prototype Java parser for display of LRG sequences
WP5: GENOMICS G2P DATABASES

Launched collaboration with Morris Schwertz to use the Molgenis software.
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
Released educational/promotional/discussion web pages on researcher IDs, via GEN2PHEN KC
 Planned the ‘IRBW2009’ Workshop on researcher IDs (CAD 2500 donated by Genome Canada)
 The ‘Indian Genome Variation’ project and database, run by Consortium members, has begun studying and databasing gene-disease relationships in India, using GEN2PHEN software
WP6: INTEGRATION AND DATA ACCESS TECHNOLOGIES

Integrated LOVD and UMD into DiseaseCard

Establish cross-referencing mechanism between EBI variant pages and Swiss-Prot variant pages.

Stress testing of new search technologies for G2P and other data

Data modelling, XML, and software development for CNV data within Ensembl

LRG Development work:
- ongoing discussions on LRG specification and rendering in human-readable HTML
- implementation: splash page, NCBI conf call, CVS, HTML, LRG mapping-annotation code
- completed first draft of Nature Genetics submission on LRG
WP7: DATA FLOWS

Held meeting to discuss LOVD data exchange issue.
WP8: GEN2PHEN KNOWLEDGE CENTER

Structure of the v2 ‘Drupalised’ Knowledge Center (KC) presented and discussed at GAM3

Tools to support training activities explored and discussed among the partners

Received curator visit (InSight: A. Dohey) to provide training on the LOVD platform
WP9: DISSEMINATION, USE AND FUTURE SUSTAINABILITY

Developed a strategy for LSDB brochures, and created generic LSDB flyer

Prepared several papers for Nature Reviews Genetics (on LRG DNA sequence), Nucleic Acids
Res. and Human Mutation (2009):
- Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C. Human
Splicing Finder: an online bioinformatics tool to predict splicing signals.
Nucleic Acids Res.
2009 Apr 1.
- Frédéric MY, Lalande M, Boileau C, Hamroun D, Claustres M, Béroud C, Collod-Béroud G.
Hum Mutat. UMD-predictor, a new prediction tool for nucleotide substitution pathogenicityapplication to four genes: FBN1, FBN2, TGFBR1, and TGFBR2.
Hum Mutat.
2009 Jan 20.
[Epub ahead of print]
- Tuffery-Giraud S, Béroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L, Moizard
MP, Bernard R, Cossée M, Boisseau P, Blayau M, Creveaux I, Guiochon-Mantel A, de
Martinville B, Philippe C, Monnier N, Bieth E, Van Kien PK, Desmet FO, Humbertclaude V,
Kaplan JC, Chelly J, Claustres M. Genotype-phenotype analysis in 2,405 patients with a
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dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum
Mutat . 2009 Jan 20. [Epub ahead of print].
- Kaput J, Cotton RGH, Hardman L, Al Aqeel AI, Al-Aama JY,Al-Mulla F, et al. Planning the
Human Variome Project: The Spain Report.
Hum Mutat.
Volume 30 Issue 4. 496 – 510.

Sponsorship of the "3rd Paris Workshop on Genomic Epidemiology".

Eight abstracts submitted to ESHG 2009, Vienna, Austria.

Abstract on GEN2PHEN submitted to Indian Society of Human Genetics conference 2009

Abstract on ETHICS submitted to The Biology of Genomes. CSH, USA.

Abstract submitted on LSDBs to the HUGO Mutation Detection Course, Paphos, Cyprus.

Abstract submitted on 'GeNS' Data Integration in the life Sciences (2009) July 20-22.

Abstract submitted on 'Supporting G2P Association Studies with Grid-enabled Workflows'.
31st Annual Int Conference of IEEE Engineering in Medicine & Biological Society.

Poster presentation on LSDBs. Dutch Society of Human Genetics meeting, Netherlands

Submitted LRG poster to British Society of Human Genetics meeting, Warwick.

Co-organised and presented talks at Biobanking Conference (Brussels, 25-27 March).

Presented LRG project to UK Clinical Molecular Genetics Society, Birmingham.

Two oral presentations on LSDB Promotion: Leiden and Utrecht, Netherlands

GEN2PHEN brochures distributed in a meeting between ULEIC Vice Chancellor and the EU
Commissioner for Research and Technical Development.

Radio interview about GEN2PHEN at "Antena 1", a Portuguese radio station.
WP10: PROJECT MANAGEMENT

Coordinated formal review processes of deliverables D1.2, D2.1, D3.2, D9.1.

Completed and submitted D10.2: “Technical and Financial Annual Reports #1”

Compiled Form Cs (cost justifications), partners’ efforts and major costs incurred.

Produced and issued minutes from GAM3 and SCM5 in Leicester.

Discussed with affected partners, and prepared forthcoming Grant Agreement amendments
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