Technology to Enable the Genomics Revolution · LIMS (genomic sequencing data) Clinician Knowledge Clinical Decision Support Tools 9. Diagnostic Tools Curation Tools Analysis (Pipeline)

Technology to Enable the Genomics Revolution

Kate Birch

Data & Technology Program Manager

How Melbourne Genomics is Delivering for Patient Care

Topics for discussion

• Delivering a shared platform for bioinformatic collaboration as part of GenoVic

• Storage of clinical genomic data as part of GenoVic

Melbourne Genomics Health Alliance | Document Name Here 2

From genetics to genomics

• Genetics scrutinizes the functioning and composition of the single gene where as

• Genomics addresses all genes and their inter relationships in order to identify their combined influence on the growth and development of the organism

World Health Organisation




Integration with microbiome, proteomics, metaboloimics...

Whole genome

Whole exome

Large panels

Small panels

Single gene



Integration with microbiome, proteomics, metaboloimics...

Whole genome

Whole exome

Large panels

Small panels

Single gene

Melbourne Genomics Health Alliance 6

An analogy…..

1000 copies of War and

Peace = a single

genome

An analogy…..


Peace = a single

genome

Shred them. Read each piece and

reconstruct the story. Find the typos.

An analogy…..


Peace = a single

genome

Shred them. Read each piece and

reconstruct the story. Find the typos.

Do they change the meaning of the

sentence?

Research Clinical care


11

Only 2% of US genomic data is used for clinical careErik Jylling - Executive Vice President Health Politics, Danish Regions

12

The Melbourne Genomic Health Alliance set out to make Victoria a world leader in the translation and use of clinical genomics in healthcare

13

Challenge: Create whole of system change

Melbourne Genomics Health Alliance




Approach


Evaluate the place of genomics in health care

practice, by:

(1) evaluating the process and outcomes of

genomic tests in practice, and

(2) establishing and applying a platform for

health service research, program evaluation,

economic evaluation and translational research

in the use of genomics in health care.

.

Establish active relationships and participation in

national and international initiatives with the aim

of disseminating, communicating and

collaborating on the work of the Alliance and its

implications.

STREAM 5: NATIONAL AND

INTERNATIONAL IMPACT

STREAM 3: INNOVATION AND RAPID ADOPTION

Develop and deploy systems to ensure patients

have access to cutting-edge, high quality genomic

testing that is cost-effective.

STREAM 1:

WORKFORCE DEVELOPMENT

Build the literacy, skills and

confidence of the clinical and

diagnostic workforce in

genomics, as relevant to each

professional role

STREAM 4: ACCESS TO GENOMIC INFORMATION

Develop and implement a single set of standards, policies

and procedures to support a common infrastructure for the

management and use of genomic data by stakeholders in

Victoria.

This stream will be the focus of the workshop.

DISEASE FLAGSHIPS

Flagships are the mechanism through which

genomic sequencing is provided to patients with

defined clinical conditions or indications.

Flagships will also be the means by which the

workforce is developed, innovation is adopted,

outcomes are evaluated and information systems

trialled, and underpin the five streams.

STREAM 2: ASSESSING THE VALUE

OF GENOMICS

Technology to enable clinical genomics

17

Access to Genomic Information


Develop and implement a single set of standards, policies and

procedures to support a common infrastructure for the

management and use of genomic data by stakeholders in

Victoria.

Ideal end state in an unconstrained environment

19

8. Clinical Tools

13. Genomic Data Repository

14. Data Integration

5. Staff to

manage the

data

PeoplePolicy & Process Technology

1. Standardised policy and

processes for data

management & access

(data governance)

11. Data Access Tools

12. Master

Patient Index

7. Identity & Access Management

2. Standardised

policy & processes

for patient consent

Electronic

Orders and

Results

EMR

(clinical data)

LIMS

(genomic

sequencing data)

Clinician

Knowledge

Clinical Decision Support

Tools

9. Diagnostic Tools

Curation Tools

Analysis

(Pipeline) Tools

10. Patient Tools

Education

Consent

Results

6. Staff to

manage the

technology

3. Standardised policy and

processes for test ordering

& reporting

4. Change control process Public variant

curation data


Diagnostic Tools Approach

21Melbourne Genomics Health Alliance

Define Requirements Procure

Prototype learnings

Future needs

LOVD

Cpipe

SeqLiner

EOI

Workshops

Pilot

Prototype

22Melbourne Genomics Health Alliance

GenoVic

G SGenomic Orchestration Service

A shared platform for bioinformatic collaboration

24

GenoVic


Bioinformatics Challenges

Pooling of resources, collaboration

Clinically hardened software

Clinical grade compute

Scalable, cost effective compute

26

DNAnexus

A platform for developing and running bioinformatics pipelines on AWS

27






28

Pipeline Design

29

Each app accepts inputs from any number of samples

• Solves code duplication

• Supports batching

Each app uses a Docker image to run the analysis

• This keeps our workflows portable

• Allows us to leverage existing containers such as the miniconda environment

Acceptance criteria outcomes - runtime

Runtime - trio

Runtime for a Ashkenazim Trio child (NA24385) is 12h 29m.

30

Framework for testing shared pipelines

The Alliance has implemented a basic framework which the laboratories can build on to implement the comprehensive pipeline testing required for accreditation.

31






32


Variant identification

DNAnexus

34

Germline Pipeline

Alliance Pipeline V1



Member's Own Pipeline

New

reference

genome?

Routine QC?

CWL/WDL?

Alt aware?

Rapid

exomes?

Long reads?





Scaleable, cost effective compute

35

Storage of clinical genomic data

36

Why store clinical genomic data?

Pathology labs need to

Reanalysis leads to new diagnoses

Clinical reference data

Valuable research data

37

GenoVic


Storage of genomic data

39

Store

Catalogue & search

Release


40

Store

Catalogue & search

Release


41

Store

Catalogue & search

ReleasePolicies and procedures for data sharing

Data Governance Owners, Stewards and Alliance Data Custodians

Patient’s views on data sharing


43

44

45

We asked patients having genomic testing what they want

Patient accept genomic testing

More than 96% of patients consented


Common

clinical consent form


Opt in to share data for activities

related to their condition

Sharing of anonymised data

Majority are informed and not concerned

Patients are informed after genetic counselling • Over 80% of patients correctly answered questions about the types of results they may receive and

storage of their data

Almost everyone agrees to additional use of re-identifiable data

• 99% agree to additional use of re-identifiable genomic data when giving clinical consent

Majority have no remaining concerns about sharing their data

• 97% received enough information about data sharing

• 93% have no remaining concerns about sharing data

• 13 had concerns (privacy, potential for discrimination – employment, insurance)


Most not worried even if they are identified


Difficult

&

concerned

Easy

&

concerned

Difficult

&

Unconcerned

Easy

&

Unconcerned

Ease of identification

&

Level of concern if

identified

How broadly should data be shared?

50

Patient trust in sharing data


Alliance Members

Australian not-for-profit

Overseas not-for-profit

Pharmaceutical

Government

Other Industry

High trust

Low trust

51

500 active health care professionals

10 organisations

>1000 received genomics CPD

Melbourne Genomics in action

16 disease areas

National and

international influence

Evaluation informing

government policy and

funding

$37.5M research and clinical

funding leveraged

Our model has been adopted by others

52

Melbourne Genomics

Health Alliance

2013-2019

Australian Genomics

Health Alliance

2016-2020

Queensland Genomics

Health Alliance

2016-2020

Genome Canada is

considering the model

Genetic Health Alliance

New Zealand

(formed in 2017)


Melbourne Genomics – 2013-2015


CEOs/LeadershipGareth Goodier (RMH)

Christine Kilpatrick (RCH)

Stephen Smith (University of Melbourne)

Doug Hilton (WEHI)

Kathryn North (MCRI)

Lynne Cobiac (CSIRO)

Sue Forrest (AGRF)

–Steering GroupJames Angus (Chair)

Julian Clark

Sue Forrest

Clara Gaff (Exec Director)

Trevor Lockett / David Hansen

Andrew Sinclair

Mike South

Paul Waring / Jon Emery

Ingrid Winship

–Advisory Groups

Information Management Advisory

David Hansen (Chair)

Terry Brennan

Ken Doig

Rowan Gronlund

Andrew Lonie

Fernando Martin-Sanchez

Wayne Mather

Emeline Ramos

Brenda White

Community Advisory

Ingrid Winship (Chair)

Louisa Di Pietro

Heather Renton

Margaret Sahhar

Janney Wale

Christine Walker

Liat Watson

Clinical Interpretation& Reporting Advisory

Paul James (Chair)

Damien Bruno

Paul Ekert

Monique Ryan

Charlotte Slade

Alison Trainer

Genomics & Bioinformatics Advisory

Graham Taylor / Alicia Oshlack (Chair)

Melanie Bahlo

Denis Bauer

Paul James

Andrew Lonie

Simon Sadedin

Kirby Siemering

Data Access Advisory

Yousef Kowsar

Kurt Lackovic

Steven Manos

Candice McGregor

Owen O’Neill

Gayle Philip

Bernie Pope

Melissa Southey

Advanced Users Group

–Flagships

AML

Andrew Roberts

Ian Majewski

Seong Lin Khaw

Francoise Merchinaud

Edward Chew

CMT

Monique Ryan

Paul James

Tim Day

Lynette Kiers

Adrienne Sexton

CRC

Alex Boussioutas

Finlay Macrae

Alison Trainer

Ingrid Winship

Michael Bogwitz

CS

Sue White

Zornitza Stark

Tiong Tan

Paul Ekert

Christiane Theda

David Amor

Maie Walsh

Patrick Yap

Epilepsy

Patrick Kwan

Terry O’Brien

Ingrid Scheffer

Piero Perucca

Paul James

–Laboratories

CTP

Paul Waring

Graham Taylor

Tiffany Cowie

Sebastian Lunke

Renata Marquis-Nicholson

Greg Corboy

Michael Christie

Arthur Hsu

VCGS

Graham Taylor

Damien Bruno

Steven Nasioulas

Belinda Chong

Shannon Cowie

Melanie Smith

Clare Love

Chris Guest

AGRF

Sue Forrest

Kirby Siemering

Melanie O’Keefe

Matthew Tinning

Lavinia Gordon

Rust Turakulov

Stephen Wilcox

–

Information SystemsCPIPE / MG LOVD VLSCI

Andrew Lonie

Simon Sadedin

John-Paul Plazzer

Charlotte Anderson

Anthony Marty

Peter Georgeson

Denis Bauer

Harriet Dashnow

Guido Grazioli

Richard Sinnott

Glenn Tesla

Clare Sloggett

Clinical Systems - MCRI & REDCAP

Jane Halliday

Susan Donath

Leanne Mills

Ross Dunn

Luke Stephens

BIOGRID

Maureen Turner

Leon Heffer

Alice Johnstone

–

Working GroupsPatient-entered data tool

Patient survey

Research access

Education symposium

Evaluation

Information requirements

Reporting

Database users

Pipeline platform

–Project TeamClara Gaff (Exec Director)

Tim Bakker (Info Mgmt)

Michele Cook (Admin)

Ivan Macciocca (Clinical)

Karen Meehan (Comms)

Natalie Thorne (Bioinf)

Evaluation Team

Emily Forbes

Melissa Martyn

Nessie Mupfeki

Bill Wilson

Genetic Counsellors

Gemma Brett

Emma Creed

Ella Wilkins

Health Economics

Khurshid Alam

Deborah Schofield

Rupendra Shrestha

Melbourne Genomics – 2016-2019


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

Thank you

Documents

Technology to Enable the Genomics Revolution · LIMS (genomic sequencing data) Clinician Knowledge Clinical Decision Support Tools 9. Diagnostic Tools Curation Tools Analysis (Pipeline)