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Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D. 04/12/2014 https://decipher.sanger.ac.uk 1

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Page 1: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Facilitating the interpretation of rare pathogenic variation in a clinical

setting with DECIPHER. Jawahar Swaminathan, Ph.D.

04/12/2014 https://decipher.sanger.ac.uk 1

Page 2: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

•  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

04/12/2014 https://decipher.sanger.ac.uk 2

Page 3: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

DECIPHER at-a-glance

https://decipher.sanger.ac.uk 04/12/2014 3

•  1300+ registered users

•  250+ Projects

•  43 countries

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

Page 4: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

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

04/12/2014 https://decipher.sanger.ac.uk 4

Registered users

only

Page 5: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Search

04/12/2014 https://decipher.sanger.ac.uk 5

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”

Page 6: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

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

04/12/2014 https://decipher.sanger.ac.uk 6

Search term:

seizures

Choose karyotype in results

Page 7: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Analysis: Prioritization and Matchmaking

04/12/2014 https://decipher.sanger.ac.uk 7

Matched Patients

Page 8: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Analysis: information •  Variant Properties •  Gene Resources

04/12/2014 https://decipher.sanger.ac.uk 8

Page 9: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Analysis: visualization

04/12/2014 https://decipher.sanger.ac.uk 9

My variant

Other Variants in DECIPHER

Overlapping CNVs

ClinVar

LSDB

Genoverse HTML5 interactive, customisable browser

Page 10: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

DECIPHER Collaborative Framework

04/12/2014 https://decipher.sanger.ac.uk 10

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

Page 11: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Collaboration

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

04/12/2014 https://decipher.sanger.ac.uk 11

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.

Page 12: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Eur J Med GenetMarch 2013

DECIPHERData from Belgium,

Netherlands

Page 13: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

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

04/12/2014 https://decipher.sanger.ac.uk 13

Research MDA

consent

Explicit consent, or publication

Page 14: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

•  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

04/12/2014 https://decipher.sanger.ac.uk 14

Page 15: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

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.

04/12/2014 https://decipher.sanger.ac.uk 15

Private

Managed

Public

Page 16: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

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)

04/12/2014 https://decipher.sanger.ac.uk 16

Page 17: Facilitating the interpretation of rare pathogenic ... · Facilitating the interpretation of rare pathogenic variation in a clinical setting with DECIPHER. Jawahar Swaminathan, Ph.D

Acknowledgements

04/12/2014 https://decipher.sanger.ac.uk

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

•  Members of the DECIPHER consortium

Ben Hutton

17

Daniel Perrett


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