From local to national registry

Prof. C. Béroud"Genetics and Bioinformatics" research team

Inserm UMR_S910, Marseille, France

From local to national registry

TREAT-NMD Global Database Oversight Committee and Curators Meeting19th -20th September 2016 - Leuven, Belgium

Background

The Universal Mutation Database (UMD) system

Generic system to build Locus Specific DataBases (LSDB)First LSDB for cancer genes in 1994 (TP53, APC)

Molecular dataEpidemiologic tools

First LSDB for Mendelian diseases in 1996 (FBN1)Phenotypic dataGenotype / phenotype

From 1996 to 2000Creation of multiple LSDBs

2001: Creation of the UMD-DMD local databaseC. Béroud in Kaplan's lab at Cochin hospital

GoalsAdded value for Diagnostic

Rapid access to molecular informationUse the existing UMD analysis functionalities

Added value for ResearchDevelop new algorithms for research (exon-skipping …)

Creation of the local UMD-DMD LSDB

New algorithms for diagnosticsEasy creation of large rearrangements (HGVS nomenclature)






New algorithms for diagnosticsMonoclonal antibodies & polymorphic markers


New algorithms for diagnosticsMonoclonal antibodies & polymorphic markers


New algorithms for diagnosticsImpact on isoforms


New algorithms for diagnosticsImpact on isoforms


New algorithms for diagnosticsExceptions to Monaco's rule


Added values for diagnostics


Easy access to all mutationsEasy input of mutations (HGVS nomenclature)

Access to Antibodies and polymorphismsImpact on isoforms

Exceptions to Monaco's rule…

All UMD functionalities(distribution and frequency of mutations ...)

New algorithms for researchexon skipping

a) Define large rearrangements profile



b) In-frame restoration of large deletions (1, 2 or 3 exons deletions)



c) Patients rescuable by a mono-skipping approach



d) Patients rescuable by a multi-skipping approach



e) Identification of splicing signals to target AONs


Added values for research


Specific tools to address the exon-skipping strategy(use patients' phenotypes)

Mono-skippingMulti-skipping

94 citations

2002: Creation of the national databaseC. Béroud in M. Claustre's lab at Montpellier hospitalS. Tuffery-Giraud (head of the DMD diagnostics)

GoalsAdded value for Diagnostic

Rapid access to molecular informationUse the existing UMD analysis functionalitiesGlobal access to French patients

Added value for ResearchDevelop new algorithms for research (phenotype data)Natural historySub-phenotypes …

Creation of the French national UMD-DMD LSDB

Creation of the national databaseUse the French network of molecular diagnostic laboratories

Two main centers (Montpellier & Paris)Established network with strong interactions

Hire a clinician (V. Humbertclaude)Define relevant itemsCollect and curate dataPerform analysis …


Creation of the national database2 molecular curators

Sylvie Tuffery-Giraud (Montpellier)France Leturcq (Paris)

2 clinical curatorsVéronique Humbert-Claude (Montpellier)Rabah Ben Yaou (Paris)


Select relevant clinical items


New algorithms for researchClinical data analysis (scoliosis)


New algorithms for researchClinical data analysis (age of onset, mean, SD, Q)


New algorithms for researchClinical data analysis (survival rate)


New algorithms for researchClinical data analysis (natural history: weight)


New algorithms for researchClinical data analysis (statistical analysis of any symptom)


New algorithms for researchClinical data analysis (graphic distribution of any symptom)


New algorithms for researchClinical data analysis (graphic distribution of any combination of symptoms)


One of the largest DMD database in the worldStrong value exemplified by publications


101 citations

In 2005, meeting with Hanns Lochmüller & Jean-Claude Kaplan at the Myology Meeting (Nantes)

➛ UMD-DMD as a model for the TREAT-NMD Global Registries


But you know this part of the story!

Lessons learned from the French UMD-DMD registry

Clearly define objectives to ensure added value for all partners

Involve all partners from the beginning geneticists, clinicians & patients

Clearly define rules may be an issue later-on (who owns what? What can you do or not?)

Think about interoperability if success, international sharing

Think about sustainability will rapidly become an issue

Think about valorization if success, industrial partners might be interested … but will also lead

to problems!

Lessons learned from the French UMD-DMD registry

Think about man-power

Local database National database

Documents

From local to national registry