clinical genomics Melbourne Genomics Health Alliance Melbourne - - PowerPoint PPT Presentation

Digital tools to enable clinical genomics

Melbourne Genomics Health Alliance

Melbourne Genomics Health Alliance

2

Medical Specialist Immersion Variant Curator Cross-training Genetic Trainee Projects Medical Scientist curation CPD workshops Clinician CPD workshops Masters of Genomics and Health Genetic Counsellor training Clinical Bioinformatics Bursaries Online CPD modules Health service research workforce Impact of Genomics (x11) Flagship Process (x 11) Flagship Health Economics (x8) Data Sharing Patient preferences, experience & value Impact on Genetic Services Additional Findings Service Baby Beyond Hearing Workforce program Implementation Factors Chromium Technology New Human Genome Reference Build Lab accreditation framework Additional Findings clinical service Additional Findings analysis service Prototype systems Data Access and Release policies and procedures Superbugs report format Implementation Framework Implementation tools (TBD) Requirements & Design Procurement Variant curation tool implementation Clinical Bioinformatics platform implementation Genome Orchestration Service Data Governance Data Security Research Environment Proof of Concept SMART on FHR feasibility study Agnostic pipeline proof of concept Ambassador program Experts-in- residence program Immersion visitor program Dissemination of results: government Stakeholder engagement Community engagement Dissemination

• f results:

public Support and contribute nationally and internationally

Workforce development Evaluation Innovation & adoption GenoVic Leadership

GenoVic

Data & Technology

4

Common Clinical Genomic Workflow

SEQUENCE DNA COLLECT DNA PERFORM BIOINFORMATIC ANALYSIS PERFORM CURATION MULTIDISCIPLINARY TEAM REVIEW GENERATE CLINICAL REPORT

CLINIC LABORATORY CLINIC & LABORATORY

PATIENT RETURN RESULTS

5

7

Glacier

Place Order Order Status Get Report View Order Details

FHIR API’s

Lab LIMS VCGS Lab Portal RMH Lab Portal Monash

LAB

FASTQ FHIR DNA DATA API TRANSFER VCF PREP FHIR

CURATION

GenoVic Full Workflow

VCF REPORT

LAB LTS

Adoption

In Use

• The Victoria Clinical Genetics Services at the Royal Childrens

Hospital

• The Royal Melbourne Hospital and the Australian Genome

Research Facility Onboarding

• Monash Health and the Australian Genome Research Facility

9

User Engagement

Data & Technology

Product Shortlist

Melbourne Genomics Health Alliance | Supplementary Information Material 11

1 2 3

Open Dialogue Limited RFP

Workshop #1 Product Discovery September 14th- 15th 2016 Workshop #2 Solution Deep Dive September 20th-21st 2016 Workshop #3 Implementation & Operations October 5th-6th 2016 Alliance evaluation and supplier assessment completed October 2016 Limited RFP Issued December 2016 EOI Briefing Session and Info Pack Released August 9th 2016 Alliance evaluation and suppliers shortlist completed August 31st 2016 Product invitation to participate in Open Dialogue September 1st 2016 EOI Supplier Response Due August 22nd 2016 Q&A Closed August 16th 2016

Pre- Qualification (EOI)

Dates may be subject to change

Variant curation tool selection

• Pilot – evaluation of each tool’s functionality and usability
• RFQ – evaluation of written response submitted by vendors

12

Evaluation Team members

13 Name Role Organisation Melanie O’Keefe Observer AGRF Thomas Mikeska Observer Austin Mat Wallis Evaluator Austin Dong Anh Khuong Quang Evaluator MCRI Asif Alam Observer Monash Greg Corboy Evaluator Monash Vivien Vasic Observer Monash Kumar Amit Observer Peter Mac Jayamala Pamar Evaluator RMH JP Plazzer Evaluator RMH Manny Sigalas Evaluator RMH Miriam Fanjul Fernandez Evaluator VCGS Sebastian Lunke Evaluator VCGS Dean Phelan Evaluator VCGS Hazel Phillimore Observer VCGS

Summary of variant curation tool pilot

28 scenarios

Evaluated quantitatively for experience and requirements

Qualitative information (comments)

If scenario couldn’t be completed How the tool could be improved Other comments

Melbourne Genomics Health Alliance | Document Name Here 14

Scenarios

• Leveraging Alliance requirements
• Ensures coverage & consistency
• Real world processes
• Scenarios cover
• System Configuration
• Quality
• Assay Setup
• Variant Filtering
• Variant Curation
• Communication

15

Curation Pilot Survey Content

Singleton Filtering Basic

• 1. Results are imported into the curation tool and are ready for filtering.
• 2. The user finds the relevant sample to work on.
• 3. The regions of interest and gene panels are assigned to the sample.
• 4. QC data is assessed.
• 5. GAP data is processed.
• 6. The sample is approved for the variant filtering to proceed.
• 7. The user reviews the default filtering and is presented with enough information to understand how it works.
• 8. The default filtering is applied and the variants of interest are identified.
• 9. Any variants that are not defined correctly are manually corrected (HGVS).
• 10. The variants are marked as requiring curation.
• 11. Some variants are marked as not for curation with justification.
• 12. A manager checks these variants to curate and amends them if required.
• 13. A final approval is given for the variants of interest and they can now be curated.

Singleton Curation Basic

• 1. A sample is ready to be curated with previously approved variants for curation.
• 2. The user finds this sample and picks the first variant to work on.
• 3. The user undertakes the curation process where the annotations provided by the curation tool are reviewed.
• 4. The annotations are weighted and classified into the relevant categories of the curation process (ACMG

• 5. The documentation for classifying variants is reviewed.
• 6. Variant specific comments are added and along with reportable comment.
• 7. The variant is given a proposed classification.
• 8. A text summarizing all the evidence used for the classification of the variant is added to the variant.
• 9. The remaining variants are curated until no more are remaining.
• 10. The sample is marked for a multi-disciplinary team meeting (MDT) to discuss further.
• 11. After MDT a confirmed classification is added to the variants.
• 12. These variants are sent to the lab to be confirmed by additional sequencing eg Sanger sequencing if required.
• 13. The results of the confirmation is recorded if applicable.
• 14. A summary text considering all the variants for the case is added to the report.
• 15. The sample is approved for reporting by a manager.

Singleton Filtering Complex

• 1. The user adds additional gene panels to the sample to expand the target region.
• 2. The user adds individual genes to the sample to expand the target region.
• 3. The user modifies the filtering process to use additional annotations.

Additional Functionality

• Pilot made clear that software required additional functionality
• Worked with evaluation team to articulate and prioritise extra

features

• Critical item were incorporated into a statement of work for the

vendor to deliver

• Other features incorporated in vendor roadmap

16

Benefits

Data & Technology

Benefits Management

18

Benefit 1: Minimise the cost and waste in administering health care

Benefit 2: Improved patient and family outcomes Benefit 3: Accelerated research and translation into patient care

Increased curation speed Increase in the appropriate use of genomics Availability of genomic data

Information Management

Support improvement in patient outcomes and disease prevention for Victorians through secure and ethical use and sharing of reliable genomic information

Reduction in the number of manual processes Reduction in the duplication of patient data (double handling) Reduction in the ordering of unnecessary and/or duplicate tests Reduction in time and effort associated with finding results Reduction in unnecessary clinical management for patients Increase in detection rates Increase the ease of access to information for clinicians & patients

• n genomics testing & results

interpretation Reduction in number of systems required to consent for research and clinical care Increased availability of genomic information for future research Increased adoption of research back into clinical practice Increase in the number and /or value of grants using genomics data from Alliance research

Early benefits

External information integrated into workflow

• Less manual work as information is centralised and integrated
• Lower maintenance, easier to update annotations

More efficient curation process

• Fewer variants to curate. Faster, better, more thorough variant

prioritisation

• Faster curation and faster second checking

Reuse of curator effort

• More comprehensive evidence collection
• More precise gene lists, and gene curation effort not wasted

| Reducing the variant curation bottleneck 19

Benefits of data sharing

Sharing curation effort

• Annotations and reference data is shared by members within

GenoVic

• Shariant integration - Sharing of curated variants across Australia

Secondary use of genomic data

• Collection of clinically generated genomic data, consented for

secondary use

• Will be available for research, methods development, validation

| Reducing the variant curation bottleneck 20

Data & Technology, Innovation & Adoption

21

Melbourne Genomics – 2016-2019

Melbourne Genomics Health Alliance | Document Name Here 22

Alliance Board

–

Executive Management Committee

–

Advisory Groups

–

Flagships 2016-2018

–

Flagships 2017-2019

–

Laboratories

–

Information Systems

–

Working Groups

–

Melbourne Genomics Health Alliance Program Team

23