digital tools to enable clinical genomics
Post on 23-May-2022
2 Views
Preview:
TRANSCRIPT
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
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
4
Common Clinical Genomic Workflow
SEQUENCE DNACOLLECT DNAPERFORM BIOINFORMATIC
ANALYSISPERFORM CURATION
MULTIDISCIPLINARYTEAM REVIEW
GENERATE CLINICAL REPORT
CLINIC LABORATORY CLINIC & LABORATORY
PATIENTRETURN RESULTS
5
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
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 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
15
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
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 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
21
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
23
top related