1. NHS GMC lab and V@R Guidance updates
Sam Clokie (WMGMC)
GEL2MDT (WMGMC and North Thames GMC collaboration)
Emma Baple (GE and South West GMC)
Update on Genomic MDT guidance
Working Part outcomes
Dom McMullan (WMGMC/ACGS)
Update on progress with RD Guidance doc

2. WGS Reporting and validation at WMRGL using GEL2MDT
Samuel Clokie, PhD
WMRGL | UoB

3. Presentation outline Project history Background on GEL2MDT
User requirements
Design principles
Overview of GEL2MDT connectivity (APIs etc)
GEL2MDT Features
Example case walkthrough – with screenshots
Future plans
Genotyping integration
Hosting
Integration with Genie
Very brief project history, before getting into the features and use-case of GEL2MDT
An insight into the connectivity of GEL2MDT.

4. Project History GOSH and BWCH working on similar idea
GOSH had developed a case management web based tool, utilising .csv files
WMRGL had started exploring CIP-API, started GUI development
…work together to produce GEL2MDT
Close collaboration has allowed rapid success with equal contribution to GEL2MDT
Like so many labs, WMRGL and GOSH were working on similar projects.

5. GOSH and WMRGL Bioinformaticians co-design and build GEL2MDT
Patrick Lombard
Theo Cole
Ed Stone
Helena Ahlfors
Samuel Clokie
GEL2MDT was written primarily by Patrick Lombard, Theo Cole and Ed Stone, with guidance and from Helena and myself.

6. User Requirements from WMRGL
Need an alternative to Excel
Create a workflow management tool to track patients progress from GEL, through MDT to report
Simple and intuitive to use
Automate data gathering (APIs)
To store discussion/actions about variants and patients during the MDT
To audit the number of cases we are processing every month
Audit the decision making process
User requirements from WMRGL side.
Needed a tool to deal with the 1000s of cases to process and considerable backlog (I don’t know precise numbers, but we have a lot to do).

7. Design principles Web based – locally or nationally hosted
Django based (ORM API)
Allow seamless integration with national bioinformatics tools/ other systems
Python.
OO approach; efficient, readable and extensible
REST API
Extensive unit tests
Backup procedure
Everyone uses Python in bioinformatics… or are moving to Python(!) [ from the famous Perl].
Extensive use of classes and class factories
Unit tests allow continual improvement.

8. GEL2MDT features
Highly normalised schema, with postgreSQL for fast performance
Utilises APIs as much as possible to integrate data sources
Hashes case JSONs, creating a history of changes
Runs VEP for HGVS
Configurable to new JSON file structures
REST API
Documentation (Sphinx)
Available on github

9. GEL2MDT connectivity APIs Re-identification
Tiered variants and decision support
Check correct panel applied
Reporting, lab systems
Check gene symbols
Calculate HGVS
Sample flow
Clinical decision and validation
Convert flat JSONs into db
Obtain PID via LabKey
Run VEP
Calculate HGVS and check gene symbols using HGNC
Design primers
Aim to get automated sample validation integrated – with simple Agena SNP assay
Some process are manual (clear boxes) automated process are in green.
Orange boxes are work in progress -
Planned
Agena MassArray
Coming soon
Manual
In progress

10. Example workflow We are now using this routinely
Talk through example stages in the text box. This workflow covers hopefully 98% of use cases
What this slide shows is the status at each stage – set in GEL2MDT
List for review saves time looking up patient in LabKey, other
Option to pull Tier 3’s at any time, e.g. useful if no clearly pathogenic found

11. Apply filters Select patient
Examples: T1 and T2s or just de novo T3s to expediate ‘no positive findings’ reports
Select patient

12. Example
workflow
List for review saves time looking up patient in LabKey, other
Option to pull Tier 3’s at any time, e.g. useful if no clearly pathogenic found

13. Update demographics and set status

14. Links to PanelApp

15. Check transcript
You can pull Tier 3 variants on demand… they are then stored for future use, no need to redownload them.

16. Example
workflow
List for review saves time looking up patient in LabKey, other
Option to pull Tier 3’s at any time, e.g. useful if no clearly pathogenic found

17. Start MDT
Search for patients
Queued cases

18. Example MDT
Export list and to clinicians

19. Assigning Cases

20. Example
workflow
List for review saves time looking up patient in LabKey, other
Option to pull Tier 3’s at any time, e.g. useful if no clearly pathogenic found

21. Example Audit page

22. Summary & Future plans Makes a multi-step pathway manageable
CIP-API and support from GEL invaluable
Eliminates reliance on excel files, reducing risk
Saves £ by reducing time needed per case/calculating manual audits
Several ways to use GEL2MDT; many linkouts
Evolving field, therefore flexible framework is useful
Open Source – available on Git
Documentation – under construction
National hosting: integration with Genie (via API)
Genotyping assay integration: Agena platform
Thanks Chris!

23. Acknowledgments Patrick Lombard (GOSH) Theo Cole (BWCH)
Ed Stone (BWCH)
Helena Ahlfors (GOSH)
BWCH:
Dom McMullan
Kirsten Mackay-Bouford
Sarah Turton
Gavin Ryan
GEL2MDT was written primarily by Patrick Lombard, Theo Cole and Ed Stone, with guidance and from Helena and myself.

24. Questions?