from local to national registry
TRANSCRIPT
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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
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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
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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
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New algorithms for diagnosticsEasy creation of large rearrangements (HGVS nomenclature)
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsEasy creation of large rearrangements (HGVS nomenclature)
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsEasy creation of large rearrangements (HGVS nomenclature)
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsMonoclonal antibodies & polymorphic markers
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsMonoclonal antibodies & polymorphic markers
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsImpact on isoforms
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsImpact on isoforms
Creation of the local UMD-DMD LSDB
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New algorithms for diagnosticsExceptions to Monaco's rule
Creation of the local UMD-DMD LSDB
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Added values for diagnostics
Creation of the local UMD-DMD LSDB
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 ...)
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New algorithms for researchexon skipping
a) Define large rearrangements profile
Creation of the local UMD-DMD LSDB
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New algorithms for researchexon skipping
b) In-frame restoration of large deletions (1, 2 or 3 exons deletions)
Creation of the local UMD-DMD LSDB
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New algorithms for researchexon skipping
c) Patients rescuable by a mono-skipping approach
Creation of the local UMD-DMD LSDB
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New algorithms for researchexon skipping
d) Patients rescuable by a multi-skipping approach
Creation of the local UMD-DMD LSDB
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New algorithms for researchexon skipping
e) Identification of splicing signals to target AONs
Creation of the local UMD-DMD LSDB
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Added values for research
Creation of the local UMD-DMD LSDB
Specific tools to address the exon-skipping strategy(use patients' phenotypes)
Mono-skippingMulti-skipping
94 citations
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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
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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 French national UMD-DMD LSDB
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Creation of the national database2 molecular curators
Sylvie Tuffery-Giraud (Montpellier)France Leturcq (Paris)
2 clinical curatorsVéronique Humbert-Claude (Montpellier)Rabah Ben Yaou (Paris)
Creation of the French national UMD-DMD LSDB
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Select relevant clinical items
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (scoliosis)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (age of onset, mean, SD, Q)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (survival rate)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (natural history: weight)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (statistical analysis of any symptom)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (graphic distribution of any symptom)
Creation of the French national UMD-DMD LSDB
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New algorithms for researchClinical data analysis (graphic distribution of any combination of symptoms)
Creation of the French national UMD-DMD LSDB
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One of the largest DMD database in the worldStrong value exemplified by publications
Creation of the French national UMD-DMD LSDB
101 citations
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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
Creation of the French national UMD-DMD LSDB
But you know this part of the story!
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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!
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Lessons learned from the French UMD-DMD registry
Think about man-power
Local database National database