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Joseph Tcherkezian-CARTaGENE
Treena McDonald-BC Generations Project
CASE STUDY: Interoperability in the Context of a Feder...
Chronic diseases
The Global Burden of Disease Study
Demographic change in Canada
Source: CIHI
Precision medicine
Source: Paving the way for
personalized medicine, FDA 2013
Giving the same
medication to all patients
i...
CARTaGENE
Awadalla P., Boileau C., 2012
3294
5566
11703
8000
979
404
937
1655
4950
147
2245
648
3436
1058
2546
1042
2321
166 235 307...
 Quantitative data with 7 000 variables per participants
 Prospective cohort
 Representative of the population (sick an...
A genetic main effect, in a candidate gene study.
Paul R Burton et al. Int. J. Epidemiol. 2009;38:263-273
Published by Oxf...
Canada’s Largest Population Health
Research Platform, 300 000 participants !
A Pan Canadian Genotyping project
within a fe...
CPTP: >300 000 participants
CPTP: Vision and Mission
Vision: Improve population health through a better
understanding of the causes of cancer and othe...
Data and biosamples
Core questionnaire
DNA containing
samples
Physical measures Urine samples
Toenail
clippings
• >300,000...
Centralized vs Federated biobanking
Harmonization and interoperability
OHS
CaG
Atlantic PATH
Online
Computerized
Teleform
Teleform
BCGP
TTP
Online
Computerize...
Requirements for Operating a Federated
Biorepository
• Standard Operating Procedures (SOP)
• Harmonize biosample data (top...
CPTP National Biosample SOP Development,
Review & Approval Procedure
Development by
Biosample Standing
Committee (BSSC)
Wo...
Confirming DNA Quality
• Conducted a CPTP DNA QC experiment
• Buffy coat and whole blood samples were proven to provide hi...
Work Flow for Releasing Biosamples:
receiving and processing approved CPTP
sample requests
• Developed pictorials and text...
CPTP Genotyping Project Goals
• Inform workflows and SOPs by identifying strengths and limitations
• Develop a cost model ...
Genotyping project
• Genotype 5000 CPTP participants on the Affymetrix UK Biobank
Axiom array gene chip (836 727 SNPs)
• P...
Request Initiation
• Confirm study requirements
– Participant selection criteria
– Regional requirements resulted in addit...
Federated Biorepository and Contracts
• You may need more than you think!
– Service agreement(s)
– Material Transfer Agree...
Federated Biorepository and Contracts
• Service contract
– Re-engaging previously used service contractor
• Can be quicker...
Sample Retrieval
• Opportunity for each cohort to create a sample retrieval list
involving a large number of samples
– Lis...
Sample Processing: Federated Biorepository
using a central laboratory
• Advantages of a central laboratory
– Fewer technic...
Sample Storage
• Processing samples almost always will result in progeny that
stay in the biorepository. Need to plan for ...
Biosample Documentation & Release
• Shipping SOP
• Genotyping was performed by a 2nd service provider. Initial
step was to...
Genotype Data Analysis
• Genotyping Files are large (2.7Gb/plate) - prearrange a sFTP site with
sufficient data capacity t...
Cost Modeling
• Developed a detailed time and resource spreadsheet, along with
instructions for how to complete
• Although...
Summary
• Inform workflows and SOPs
• Able to test the administrative component of providing samples for approved
requests...
Acknowledgement
Philip Awadalla Jason Hicks
John Spinelli Melissa Moore
Mark Purdue Kelly McDonald
Trevor Dummer Catherine...
CPTP Portal: Single Point of Access
https://portal.partnershipfortomorrow.ca/
32
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CARTaGENE: Challenges and benefits of a federated biorepository model - October 6, 2016

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Title: Challenges and benefits of a federated biorepository model

Abstract:Genome-based studies have provided powerful research tools for identifying genetic variants that contribute to chronic diseases. Recognition is growing, however, that chronic diseases are caused by a combination of an individual's genetic predisposition and their exposure to certain environmental risk factors. CARTaGENE was created to support the scientific community in identifying the determinants of chronic diseases of environmental and/or genetic origin. It was also created to accelerate the process of translational medicine through the identification of biomarkers for early diagnosis, disease treatment and prevention. To be competitive with the rest of the world and to increase the statistical power of its data, CARTaGENE has joined forces with four other Canadian cohorts to form the Canadian Partnership for Tomorrow Project (CPTP, http://www.partnershipfortomorrow.ca/). CPTP is the largest population based cohort study in Canada with over 300 000 participants recruited. In 2015 a CPTP Genotyping Project was launched to test drive CPTP’s biosample release procedures to help inform time and resource requirements and to identify challenges that may be present within the federated biorepository model under which the study operates. The project design included specific participant inclusion criteria, sample retrieval, DNA extraction, and genotyping of 5,000 samples. Lessons learned from this project will be shared.

For more information about biosample and data access: access@cartagene.qc.ca

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CARTaGENE: Challenges and benefits of a federated biorepository model - October 6, 2016

  1. 1. Joseph Tcherkezian-CARTaGENE Treena McDonald-BC Generations Project CASE STUDY: Interoperability in the Context of a Federated Biobanking Project
  2. 2. Chronic diseases The Global Burden of Disease Study
  3. 3. Demographic change in Canada Source: CIHI
  4. 4. Precision medicine Source: Paving the way for personalized medicine, FDA 2013 Giving the same medication to all patients is expensive, not very efficacious and causes severe adverse effects.
  5. 5. CARTaGENE
  6. 6. Awadalla P., Boileau C., 2012 3294 5566 11703 8000 979 404 937 1655 4950 147 2245 648 3436 1058 2546 1042 2321 166 235 307 263 883 20712007 1114 289 5051 2604 102 3232 296 4782 217 44 96 3387 0 2000 4000 6000 8000 10000 12000 14000 Diabète Désordrethyroidien Hypercholestérolémie Hypertension Angine AVC IM Bronchitechronique Asthme Insuffisancerénale Calculsrénaux Infectionsrénales Ostéoarthrite Arthriterhumatoide Ostéoporose Glaucome Cataractes Dégénérescencemaculaire Cirhose Hépatitechronique Cholecystite Ulcère/refluxacide Syndromecôlonirritable Polype Diverticulite MaladiedeCrohn Eczéma Psoriasis Lupusérythémateuxdisséminé Dépressionmajeure Épilepsie Migraine Scléroseenplaques MaladiedeParkinson Schizophrénie Cancers Nombredeparticipants Chronic diseases in CaG cohort
  7. 7.  Quantitative data with 7 000 variables per participants  Prospective cohort  Representative of the population (sick and healthy)  Linkage with administrative medial records  Genetically homogeneous population (founder effect) Unique features
  8. 8. A genetic main effect, in a candidate gene study. Paul R Burton et al. Int. J. Epidemiol. 2009;38:263-273 Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2008; all rights reserved. Uncommon and Common G*E interaction Power calculation for genetic association study of common complexe diseases
  9. 9. Canada’s Largest Population Health Research Platform, 300 000 participants ! A Pan Canadian Genotyping project within a federated cohort
  10. 10. CPTP: >300 000 participants
  11. 11. CPTP: Vision and Mission Vision: Improve population health through a better understanding of the causes of cancer and other chronic diseases. Mission: To create and sustain a pan-Canadian population health platform that promotes and supports high quality, innovative population and health research.
  12. 12. Data and biosamples Core questionnaire DNA containing samples Physical measures Urine samples Toenail clippings • >300,000 • Demographics • Lifestyle • Risk factors • Several others • Venous blood collection (>143,000) • Blood spots (>28,000) • Saliva (>8,000) • Up to 90,000 • Height/weight • Waist/hip circumference • BMI • Grip strength • 101,000 • >30,000
  13. 13. Centralized vs Federated biobanking
  14. 14. Harmonization and interoperability OHS CaG Atlantic PATH Online Computerized Teleform Teleform BCGP TTP Online Computerized Online Paper Version 1 Version 2 2 questionnaire versions Isabel Fortier, Maelstrom Research Group Computerized Computerized Computerized
  15. 15. Requirements for Operating a Federated Biorepository • Standard Operating Procedures (SOP) • Harmonize biosample data (topic for another discussion) • Administrative procedures for receiving and processing approved CPTP sample requests to facilitate biosample release The above takes longer to finalize than if operating a central biorepository
  16. 16. CPTP National Biosample SOP Development, Review & Approval Procedure Development by Biosample Standing Committee (BSSC) Working Group Review by BSSC - Major changes may require further work by SOP Working Group Regional Review of BSSC Approved SOP Regional Feedback presented to BSSC -major changes require 2nd regional review OSC Review & Approval of Submitted Draft SOP Sign-off by OSC designate
  17. 17. Confirming DNA Quality • Conducted a CPTP DNA QC experiment • Buffy coat and whole blood samples were proven to provide high quality DNA of good yield. • Blood spots prove to provide high quality DNA in 95% of samples with lower and more variable yields than buffy coat and whole blood.
  18. 18. Work Flow for Releasing Biosamples: receiving and processing approved CPTP sample requests • Developed pictorials and text to describe how work flow would occur • Identified 5 areas: request initiation, sample retrieval, sample processing, sample storage, sample documentation & release • Regions identify limitations/challenges for each of the 5 areas • Information presented to the CPTP Operational Steering Committee for input Resulted in the CPTP Genotyping Project
  19. 19. CPTP Genotyping Project Goals • Inform workflows and SOPs by identifying strengths and limitations • Develop a cost model using project obtain data on time, resource and cost requirements • Strengthen the resource by supplying a densely genotyped sub cohort that can serve as a control group for future genomic research projects
  20. 20. Genotyping project • Genotype 5000 CPTP participants on the Affymetrix UK Biobank Axiom array gene chip (836 727 SNPs) • Participant eligibility criteria included: – Stored buffy coat or whole blood – Age 40-69 years at baseline – Completed all aspects of the study (questionnaires, physical measures) – Cancer free at baseline – Excluded participants who already had extracted DNA or were of non-European ancestry – 50% female, 50% male – Regional specific criteria (e.g. if other data were available on the participants)
  21. 21. Request Initiation • Confirm study requirements – Participant selection criteria – Regional requirements resulted in additional considerations when insufficient numbers of participants per sub-group were identified. – >5,000 participants were selected in case insufficient DNA was available. • Decide where the work will be performed • Arrange service contracts
  22. 22. Federated Biorepository and Contracts • You may need more than you think! – Service agreement(s) – Material Transfer Agreement(s) – Data Transfer Agreement(s) • Consider the time requirement • Designate a study administrative/laboratory lead to help move the process along One Federated agreement
  23. 23. Federated Biorepository and Contracts • Service contract – Re-engaging previously used service contractor • Can be quicker to initiate service contract • Don’t assume same service contract terms are applicable if the dollar amount of work increases – Engaging a new service contractor • New territory so expect some time to complete contract – If a federated agreement not available then MTA may also be required • Material Transfer Agreements and Data Transfer Agreements – Harmonize on work description – Harmonize, whenever possible or required, the legal text
  24. 24. Sample Retrieval • Opportunity for each cohort to create a sample retrieval list involving a large number of samples – List are regional specific and therefore allowed each cohort to test their processes and format – Identified the need to not only include sample ID but also sample type • Opportunity to performed sample location QA checks – i.e. was the sample in the place you intended it to be • Cost modeling data was obtained for personnel and supplies
  25. 25. Sample Processing: Federated Biorepository using a central laboratory • Advantages of a central laboratory – Fewer technicians involved so less personnel inter-variability – Access to robotics – Frees up time in the regions to perform other duties – Standardized data format • Disadvantages of a central laboratory – May require administrative time to finalize legal agreements – Less control – Need to consider all possible processing factors upfront (could also be an advantage!) – The processing rate may be slower as fewer technicians involved – Requires uploading of external data into regional LIMS
  26. 26. Sample Storage • Processing samples almost always will result in progeny that stay in the biorepository. Need to plan for storage
  27. 27. Biosample Documentation & Release • Shipping SOP • Genotyping was performed by a 2nd service provider. Initial step was to perform sample QA on 8% of samples – benefit as it confirms input sample quality.
  28. 28. Genotype Data Analysis • Genotyping Files are large (2.7Gb/plate) - prearrange a sFTP site with sufficient data capacity to allow for file transfer • Define your QC approach prior to obtaining the results • Confirm sex, ethnicity & identify relatedness between samples • In 960 BC samples analyzed on the UK Biobank Array: – >98% of samples had a call rate >99% – 6% of sites were monomorphic, 2.5% of sites were out of HWE, and 11% of sites had a MAF <1%. – One pair of siblings was identified – All samples were of western European ethnicity
  29. 29. Cost Modeling • Developed a detailed time and resource spreadsheet, along with instructions for how to complete • Although much time and effort had been put into the spreadsheet it wasn’t always clear for personnel where and if something was to be recorded • Feedback overwhelmingly indicated that the time data is an estimate • Regional time differences were identified, although this was less pronounce when multiple steps were grouped
  30. 30. Summary • Inform workflows and SOPs • Able to test the administrative component of providing samples for approved requests • Better insight into the required legal agreements • Provides guidance for how best to provide samples for approved requests • Develop a cost model • Better understanding of the time and cost requirements • Strengthen the resource – DNA available on a subset of CPTP participants – Extracted DNA is of high quality as demonstrated by the ability to meet the Axiom gene chip requirements – Will soon have genotype data on 5000 CPTP “healthy” Caucasian individuals
  31. 31. Acknowledgement Philip Awadalla Jason Hicks John Spinelli Melissa Moore Mark Purdue Kelly McDonald Trevor Dummer Catherine Boileau Paula Robson Wendy Powell Sebastien Jacquemont Heather Whelan Anne Monique Nuyt Linda Greenhorn Louise Parker Will Rosner Alexandra Obadia Genevieve David Anne-Marie Mes-Masson Jason Xu Isabel Fortier Brenda Hahn Bartha Knoppers Vanessa Bruat Funding provided by Canadian Partnership Against Cancer
  32. 32. CPTP Portal: Single Point of Access https://portal.partnershipfortomorrow.ca/ 32

Title: Challenges and benefits of a federated biorepository model Abstract:Genome-based studies have provided powerful research tools for identifying genetic variants that contribute to chronic diseases. Recognition is growing, however, that chronic diseases are caused by a combination of an individual's genetic predisposition and their exposure to certain environmental risk factors. CARTaGENE was created to support the scientific community in identifying the determinants of chronic diseases of environmental and/or genetic origin. It was also created to accelerate the process of translational medicine through the identification of biomarkers for early diagnosis, disease treatment and prevention. To be competitive with the rest of the world and to increase the statistical power of its data, CARTaGENE has joined forces with four other Canadian cohorts to form the Canadian Partnership for Tomorrow Project (CPTP, http://www.partnershipfortomorrow.ca/). CPTP is the largest population based cohort study in Canada with over 300 000 participants recruited. In 2015 a CPTP Genotyping Project was launched to test drive CPTP’s biosample release procedures to help inform time and resource requirements and to identify challenges that may be present within the federated biorepository model under which the study operates. The project design included specific participant inclusion criteria, sample retrieval, DNA extraction, and genotyping of 5,000 samples. Lessons learned from this project will be shared. For more information about biosample and data access: access@cartagene.qc.ca

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