Digital tools to enable clinical genomics

Melbourne Genomics Health Alliance

Melbourne Genomics Health Alliance

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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

ProcurementVariant curation

tool implementation

Clinical Bioinformatics

platform implementation

Genome Orchestration

Service

Data Governance

Data SecurityResearch

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 of results:

public

Support and contribute

nationally and internationally

Workforce

development

Evaluation

Innovation

& adoption

GenoVic

Leadership

GenoVic

Data & Technology

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Common Clinical Genomic Workflow

SEQUENCE DNACOLLECT DNAPERFORM BIOINFORMATIC

ANALYSISPERFORM CURATION

MULTIDISCIPLINARYTEAM REVIEW

GENERATE CLINICAL REPORT

CLINIC LABORATORY CLINIC & LABORATORY

PATIENTRETURN RESULTS

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7

Glacier

Place

Order

Order

StatusGet

Report

View Order

Details

FHIR

API’s

Lab LIMS

VCGS

Lab Portal

RMH

Lab Portal

Monash

LAB

FA

ST

Q

FH

IR

DN

A

DATA

AP

I

TRANSFER

VC

F

PREP

FH

IR

CURATION

GenoVicFullWorkflow

VCF

REPORT

LAB

LTS

Adoption

In Use

• The Victoria Clinical Genetics Services at the Royal ChildrensHospital

• The Royal Melbourne Hospital and the Australian Genome Research Facility

Onboarding

• Monash Health and the Australian Genome Research Facility

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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

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Evaluation Team members

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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 scenariosEvaluated 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

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Curation Pilot Survey Content This is a set of scenarios that the Alliance may be using to assess the curation tool in line with the requirements. This can

be used to help guide the planning of the training that will be delivered to the assessors.

Singleton Filtering Basic A single sample is imported with easy to find pathogenic variants. Pre-configured filtering is applied and the relevant

variants are marked for curation.

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 A single sample with variants that have easily available evidence to support a diagnosis.

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

guidelines or custom weighting matrix) until there is sufficient evidence for a diagnosis.

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 A single sample with difficult to identify pathogenic variants that required manual filtering steps to be undertaken. The

target region is expanded. The use of multiple annotations is required to identify variants of interest, eg Clinvar. This is

the same process as the basic filtering except for the following:

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

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Benefits

Data & Technology

Benefits Management

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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 speedIncrease in the appropriate use of

genomicsAvailability 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

on 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

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Melbourne Genomics – 2016-2019

Melbourne Genomics Health Alliance | Document Name Here 22

Alliance BoardCatherine Walter (Chair)Christine Kilpatrick (RMH)Andrew Stripp (Monash Health)Dale Fisher (PeterMac)Christine Kilpatrick (RCH)Shitij Kapur (UoM)Doug Hilton (WEHI)Kathryn North (MCRI)Rob Grenfell (CSIRO)Irene Kourtis (AGRF)Sue Shilbury (Austin Health)Anna Burgess (DHHS observer)

–Executive Management CommitteeClara Gaff (Chair)David HansenAndrew SinclairRichard KingJulian ClarkFelicity ToppFergus KerrPeter McDougallIngrid WinshipSean GrimmondKirby SiemeringPaul Fennessy (DHHS observer)

–Advisory Groups Clinical Adoption Advisory

Fergus Kerr (Chair)Cate Kelly Sylvia Metcalfe Don CampbellLindsay GraysonMargaret Kelaher Noel CranswickJayesh Desai

Community Advisory

Jane Bell (Chair)Louisa Di PietroHeather RentonMargaret SahharJanney WaleChristine WalkerLiat Watson

Diagnostic Advisory

Richard King (Chair)Kirby SiemeringSebastian Lunke Melanie O’KeefeVivien VasicMichael ChristieAndrew FellowesSuzanne SvobodovaTony Papenfuss Simon SadedinPaul James

Information Management Advisory/GenoVic Project Control Group

David Hansen (Chair)Wayne Mather Rowan GronlundKevin EricksenTony Papenfuss Michael CarolanErminia SchiavoneKris JenkinsMike SouthAngela WattAndrew LonieClara GaffMalcolm Smart

–Flagships 2016-2018Congenital Deafness

David AmorLilian DownieValerie SungLibby SmithBibi GernerMatthew HunterKerryn SaundersNatasha BrownMelissa WakeRachel BurtJane HallidayZeffie PoulakisElizabeth Rose

Complex Care in Children

Sue WhiteZornitza StarkTiong TanAlison YeungMatthew HunterKatrina Harris

Dilated Cardiomyopathy

Paul JamesJay RamchandMatthew WallisDavid HareOmar Farouque

Immunology

Jo DouglassCharlotte SladeVanessa BryantJo SmartSara BarnesSeth MastersMimi TangIngrid WinshipZornitza Stark

Lymphoma

Stephen OpatMiles PrinceGareth GregoryMichael DickinsonEliza HawkesPiers Blombery

Solid Cancers

Jayesh DesaiKortnye SmithSophie BeckDong Anh Khuong QuongHui GanPaul EckertBen SolomonBen Markman

–Flagships 2017-2019Bone marrow failure

Piers BlomberyDavid RitchieFrancoise MechinaudAnthea GreewayAndrew GriggErica WoodPaddy Barbaro

Controlling Superbugs

Lindsay GraysonBen HowdenNorelle SherryJason KwongTony Korman

Caroline MarshallMark ChanMonica SlavinMarcel Leroi

Complex neurological

Patrick KwanSam BerkovicMartin DelatyckiDennis VelakoulisMichael FaheyMelanie BahloRick LeventerAmy Schneider

Genetic kidney disease

Catherine QuinlanSue WhiteZornitza StarkElla WilkinsMathew WallisDavid PowerKathy NichollsPeter Kerr

Perinatal autopsy

George McGillivrayJacqueline CollettIan SimpsonTrishe LeongJan PymanAlison YeungNatasha BrownSue WhiteSue Walker

–LaboratoriesCTP

Paul WaringGraham TaylorTiffany CowieSebastian LunkeRenata Marquis-NicholsonGreg Corboy

Michael ChristieArthur Hsu

VCGS

Graham TaylorDamien BrunoSteven NasioulasBelinda ChongShannon CowieMelanie SmithClare LoveChris Guest

AGRF

Sue ForrestKirby SiemeringMelanie O’KeefeMatthew TinningLavinia GordonRust TurakulovStephen Wilcox

–Information SystemsCPIPE / MG LOVD VLSCI

Andrew LonieSimon SadedinJohn-Paul PlazzerCharlotte AndersonAnthony MartyPeter GeorgesonMichael MiltonJuny KesumadewiGayle PhilipsDenis BauerHarriet DashnowGuido GrazioliRichard SinnottGlenn TeslaClare Sloggett

Clinical Systems - MCRI & REDCAP

Jane HallidaySusan DonathLeanne MillsRoss DunnLuke StephensBIOGRIDMaureen TurnerLeon HefferAlice Johnstone

–Working GroupsPatient-entered data toolPatient surveyResearch accessEducation symposiumEvaluationInformation requirementsReportingDatabase usersPipeline platformCuration tool pilot evaluatorsCuration tool RFQ evaluatorsAnalysis tool user groupCuration tool user groupInformation architecture reference group

–Genetic Counsellors

Gemma BrettEmma CreedAnna JarmolowiczIvan MaccioccaEllie PrawerGiulia ValenteKirsty West

Health Economics

Khurshid AlamDeborah SchofieldRupendra Shrestha

Melbourne Genomics Health Alliance Program Team

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