facilitating the interpretation of rare pathogenic ... · facilitating the interpretation of rare...

Facilitating the interpretation of rare pathogenic variation in a clinical

setting with DECIPHER. Jawahar Swaminathan, Ph.D.

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•  Aiding the interpretation of genomic variants since 2004

•  Primary Objective Facilitate identification and interpretation of pathogenic genetic variation in rare disorders

•  Mission making genetic and phenotypic data discoverable to enable improved interpretation of variation that cannot be unambiguously interpreted in isolation

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DECIPHER at-a-glance

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•  1300+ registered users

•  250+ Projects

•  43 countries

•  40K+ patient records (52k variants) •  ~15K shared publicly (anonymised). •  10K+ under managed access

Deposition •  Patient Info •  Variant (CNV/SNV) •  Phenotypes (HPO) •  Bulk or single upload

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Registered users

only

Search

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Searching publicly shared data does not require login. Logged in user search results take into account user access

Coming soon: Advanced Search e.g “seizures and 20q13.3”

Analysis: Search Results Karyotype view of Chr 20 for patients with phenotype “Seizures”

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Search term:

seizures

Choose karyotype in results

Analysis: Prioritization and Matchmaking

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Matched Patients

Analysis: information •  Variant Properties •  Gene Resources

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Analysis: visualization

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My variant

Other Variants in DECIPHER

Overlapping CNVs

ClinVar

LSDB

Genoverse HTML5 interactive, customisable browser

DECIPHER Collaborative Framework

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Peer-to-Peer Between DECIPHER registered users on patients on mutual interest using “Contacts” option.

External User to Peer DECIPHER mediates contact and collaboration requests from external to registered users

Bulk anonymous data for research Available to bona fide researchers under Data Access and Display agreements.

Programmatic Access Development of API as part of the GA4GH and Matchmaker Exchange initiatives

In Progress

Collaboration

DECIPHER members can contact each other directly. DECIPHER also forwards over 50 external contact requests every year.

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Since 2011, 600+ publications have used shared DECIPHER data.

Data from any rare disease study that collects phenotype-linked variation data can be analyzed and shared from within DECIPHER.

Eur J Med GenetMarch 2013

DECIPHERData from Belgium,

Netherlands

DECIPHER Data Model

•  Private – visible to depositing project only

•  Managed: Visibility restricted to users of named consortia

•  Public – anonymised data available to all after patient consent

Managed sharing allows data (research or clinical) to be shared between collaborators and named consortia without being available to all.

Private

Public

Clinical

Managed

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Research MDA

consent

Explicit consent, or publication

•  Patient can be public or private

•  Variants in a patient can be •  Not shared •  Shared with one or more

consortia (anonymised) •  Shared publicly (fully

anonymised)

•  Limited sharing reaches more people than unshared.

•  Public sharing reaches a vastly greater audience.

Sharing

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Sharing Customisable sharing of variant within a patient

Variant visibility depends on patient consent status and user access level. A variant can only be seen by public if the patient has given appropriate consent.

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Private

Managed

Public

DECIPHER’s 10 year experience - thoughts

•  Building depositor trust, engender a sharing ecosystem •  Meeting varied user needs (clinical, lab, research) •  Catering to both research and clinical communities •  Information depth vs. usability •  Easy availability of data (search, API, bulk download)

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Acknowledgements

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•  Patients and families for permission to include their data in DECIPHER

•  Members of the DECIPHER consortium

Ben Hutton

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Daniel Perrett