Ten projects being led and co-led by UBC researchers have been awarded $101m through Genome Canada and Genome BC in collaboration with the Canadian Institutes of Health Research, provincial government and project co-funding partners, through the Large Scale Applied Research and the Genomics Technology Platforms competitions.
2017 Large Scale Applied Research Project Competition: Genomics and Precision Health
The Genome Canada 2017 Large-Scale Applied Research Project Competition: Genomics and Precision Health, a partnership with the Canadian Institutes of Health Research (CIHR), is dedicated to bringing precision health research to the clinic where it will improve outcomes for Canadian patients.
Eight of the fifteen funded projects are led by researchers at UBC and its affiliated teaching hospitals, receiving $80.3m:
Silent Genomes: Reducing health-care disparities and improving diagnostic success for Indigenous children with genetic disease
Project leaders: Laura Arbour (University of British Columbia), Nadine Caron (University of British Columbia), Wyeth W. Wasserman (BC Children’s Hospital Research Institute & University of British Columbia)
Genome Centre: Genome British Columbia
Total funding: $10.4 million
First Nations, Inuit and Métis’ populations, collectively known as the Indigenous Peoples’ of Canada, face strikingly similar health challenges with global Indigenous Peoples’. Inequities include barriers to healthcare access that produce poorer health outcomes compared to non-Indigenous groups.
Whereas genomic technologies are advancing health care by allowing medical treatments to be tailored to the specific needs of individual patients (‘precision medicine’), this ‘genomics revolution’ is widening the health inequities gap. In particular, compared to what is becoming routinely available to other Canadians, Indigenous populations often have little or no access to genomic technologies and the research that drives them, hence intensifying the ‘genomic divide’.
A key concern in the growing genomic divide is the lack of background genetic variation data for Indigenous populations living in Canada and globally. This prevents accurate diagnosis because the reference data are needed for precise genetic diagnosis. Notably, standard genomics resources are silent with respect to First Nations (FN), Inuit and Métis’. Silent Genomes will address the genomic divide by reducing access barriers to diagnosis of genetic disease in Indigenous children.
Silent Genomes, is a game changing partnership with First Nations, Inuit and Métis Peoples that will:
- establish processes for Indigenous governance of biological samples and genome data,
- lead to policy guidelines and best practice models, bringing equitable genomic testing to Indigenous children in Canada with suspected genetic diagnosis, and
- develop an Indigenous Background Variant Library (IBVL) of genetic variation from a diverse group of First Nations in Canada.
Silent Genomes will improve health outcomes by enhancing equitable access to diagnosis, treatment, and care while assessing cost effectiveness of precision medicine
Genomic and outcomes database for pharmacogenomics and implementation studies (GoPGx)
Project leaders: Bruce C. Carleton and Colin J. Ross (University of British Columbia)
Genome Centre: Genome British Columbia
Total funding: $9.9 million
Adverse drug reactions (ADRs) are a major problem in modern medicine, leading to withdrawal of treatment, non-compliance with medication, permanent disability and death. This is particularly true for cancer treatment, with its potent medications. The vision of Go-PGx is to save lives and improve the quality of life of children with cancer, by using genomics-based precision health strategies to reduce the most common and serious ADRs in these children.
It is increasingly evident that genetic differences in patients can affect the likelihood of their developing an ADR. Drs. Bruce C. Carleton and Colin J. Ross, both of the University of British Columbia, are working to prevent these ADRs by developing lab tests to predict the likelihood of a childhood cancer patient developing an ADR and tools to incorporate these tests into clinical practice. Through Go-PGx, they will analyze more than 6,125 DNA samples and corresponding medication use and ADR outcome data to discover biomarkers that will reveal genetic susceptibility to ADRs and develop tools to educate and inform physicians and patients, beginning with five of the most severe ADRs in childhood cancer. They will also develop a comprehensive database linking clinical and genetic data as an accessible resource for researchers throughout the world. With the data they generate, they will begin providing testing at 10 pediatric cancer centres across Canada, while studying barriers and facilitators to the uptake of ADR screening in the health-care system, as well as the economic implications of introducing this kind of testing into clinical practice. The team will also develop peer-reviewed clinical practice guidelines before the project’s end and publish them within a year post-project.
Precision Medicine CanPREVENT AMR: Applying precision medicine technologies in Canada to prevent antibody-mediated rejection and premature kidney transplant loss
Project leaders: Paul Keown (University of British Columbia), Ruth Sapir-Pichhadze (McGill University), Timothy Caulfield (University of Alberta), Stirling Bryan (University of British Columbia)
Genome Centres: Genome British Columbia (administrative lead), Génome Québec, Genome Alberta
Total funding: $9.7 million
Transplantation is the treatment of choice for patients whose kidneys have failed, providing superior survival, better quality of life and lower health-care system costs (<$20,000/year vs. > $90,000) compared with dialysis. However, a severe form of rejection (known as antibody-mediated rejection, or AMR) causes premature loss of the transplant kidney in as many as 30 per cent of transplant recipients, or 500 Canadians every year, prompting a return to dialysis and often early death.
The team led by Drs. Paul Keown and Stirling Bryan of the University of British Columbia, Ruth SapirPichhadze of McGill University and Timothy Caulfield of the University of Alberta, which includes over 70 scientists and clinicians from 22 universities in Canada, the US, the UK and the EU, will use genomic technologies to reduce the risk of AMR. These will enable better matching of patients and donors, precise monitoring of the immune response after transplantation to better predict AMR, and the use of personalized drug treatments to prevent rejection while avoiding infection or cancer. The team will also engage patients, providers and health care payers to study the legal, ethical, societal and economic considerations of introducing these strategies into clinical practice.
The goals of the research program are to reduce the frequency of AMR by at least 50 per cent and in so doing to benefit first the patient and his or her family through improved survival and quality of life, reduced caregiver burden and personal health costs; second to minimize demand on the health-care system by reduced costs through decreasing dialysis and re-transplantation, and third to improve societal care of a major chronic disease by increasing productivity and streamlining the management of chronic kidney failure.
Deciphering the genome biology of relapsed lymphoid cancers to improve patient management
Project leaders: Christian Steidl, Marco Marra and David Scott (BC Cancer Research Centre and University of British Columbia)
Genome Centre: Genome British Columbia
Total funding: $11.9 million
Lymphoid cancers, which start in the immune system and include Hodgkin’s and non-Hodgkin’s lymphoma, myeloma, lymphocytic, and lymphoblastic leukemia, are the fifth-most-common cancers in both men and women and affect people of all ages. Every year in Canada, 16,000 people are diagnosed with a lymphoid cancer and 6,000 die from them. Death most often happens when disease relapses after an initially successful treatment, making treating and controlling the symptoms of relapsed disease the most pressing need for patients suffering from lymphoid cancers.
Because the causes of relapse are not known, and because relapsed cancer differs considerably from the initial cancer, there are no clinical tests to provide information on the prognosis for individual patients and likely treatment outcomes, or to provide guidance to physicians and patients on the use of alternative therapies, such as small molecule drugs or immunotherapy. Relapses and associated treatments cost the Canadian health-care system more than $315 million each year, about 10 per cent of the expected cancer drug budget in 2022, and the lack of clinical tests means many of these expensive treatments are applied without adequate guidance.
Drs. Christian Steidl, Marco Marra and David Scott of the BC Cancer Research Centre are developing genomics-based clinical tests to improve patient outcomes and quality of life, and working to integrate the tests in the health-care system. To do so, they will sequence relapsed tumours to identify novel biomarkers. They will undertake economic analyses to better understand the cost-effectiveness and health-system impact of genomics-informed management of relapsed disease. They will also develop an e-health application to assist patients with shared decision-making.
The results of this project will be novel clinical tests that will provide decision aids for physicians and patients, help policy makers in implementing personalized treatment approaches for relapsed lymphoid cancers and reduce the costs of treating relapsed lymphoid cancers. 4 Childhood asthma and the microbiome – precision health for life:
The Canadian Healthy Infant Longitudinal Development (CHILD) study
Project leaders: Stuart Turvey, Michael Kobor, Brett Finlay (University of British Columbia), Padmaja Subbarao (The Hospital for Sick Children)
Genome Centres: Genome British Columbia (administrative lead), Ontario Genomics
Total funding: $9.1 million
Asthma is the most common chronic disease of childhood, affecting one in seven Canadian children (and more than three million Canadians of all ages). It is the most common reason for children to be admitted to hospital and for them to miss school. It is also expensive, costing more than $2 billion per year in Canada. Treatments can manage symptoms, but there is no cure, only the slight hope that children will “grow out of it.”
Dr. Stuart Turvey, his team at the University of British Columbia and the CHILD study team are focusing on early diagnosis and prevention, two factors that can reduce the personal and economic toll of asthma. Their sample of choice comes from dirty diapers: by using powerful genomics technologies to analyze stools, they may be able to predict which infants will go on to develop asthma. The reason? Evidence has shown that babies who go on to develop asthma tend to be missing key microbes in their intestines (the microbiome, as it is known) in the first few months of life. Beyond predicting who may develop asthma, thus enabling early diagnosis, the research will guide the ethical development of ways to replace these microbes, to prevent asthma from developing at all.
GenCOUNSEL: Optimization of genetic counselling for clinical implementation of genomewide sequencing
Project leaders: Alison M. Elliott (BC Provincial Health Services Authority), Bartha Knoppers (McGill University), Larry Lynd (University of British Columbia), Jehannine Austin (University of British Columbia)
Genome Centres: Genome British Columbia (administrative lead), Génome Québec
Total funding: $4.2 million
Genome-wide sequencing (GWS; whole genome or exome sequencing) is a powerful new genetic test that analyzes a person’s entire genetic make-up. While valuable, it can be problematic, by revealing disorders or disease risk factors unrelated to the original reason for testing, or by generating complex findings that are difficult for non-expert health providers to interpret. While not currently routinely available, genome-wide sequencing will soon be in more widespread use for patients who need it – increasing demand for genetic counselling, to which access is already limited in Canada.
Genetic counsellors provide education and emotional and decisional support to patients and families, helping them to make informed decisions about genetic testing and its results. Because of lack of legal recognition of genetic counsellors in Canada, most of them are found in academic centres rather than in the community.
GenCOUNSEL, which brings together experts in genetic counselling, genomics, ethics, health services implementation and health economics research, is the first project to examine the genetic counselling issues associated with clinical implementation of GWS. It will determine the most efficient socioeconomic, clinical, legal and economic methods of providing genetic counselling once GWS is available in the clinic. It will create an understanding of current and future needs for genetic counselling, develop 5 best practices for the delivery of genetic counselling, improve access to the counselling, particularly for underserved patient populations, and study the feasibility of different models of legal recognition of genetic counsellors. The result will be increased access, patient satisfaction and cost-efficiency while helping to make genetic counselling available to all Canadians who need it.
Care4Rare Canada: Harnessing multi-omics to deliver innovative diagnostic care for rare genetic diseases in Canada (C4R-SOLVE)
Project leaders: Kym Boycott (Children’s Hospital of Eastern Ontario Research Institute), Michael Brudno (The Hospital for Sick Children), François Bernier (University of Calgary), Clara van Karnebeek, (University of British Columbia)
Genome Centres: Ontario Genomics (administrative lead), Genome Alberta, Genome British Columbia
Total funding: $12.9 million
There are more than 7,000 rare genetic diseases in Canada, which have a devastating impact on some one million Canadians and their families: two-thirds of these diseases cause significant disability; threequarters affect children; more than half lead to early death; and, almost none has any targeted 6 treatment. Further, more than one-third of these diseases remain unsolved (their genetic cause is unknown). Building on the work of the Care4Rare Canada Consortium, the C4R-SOLVE project is working to identify the genetic cause of unsolved rare diseases and make genomic sequencing available to Canadians for rare disease diagnosis. Genomic sequencing will speed up the diagnostic process, thereby ending or even preventing years of diagnostic testing and visits to multiple specialists. Providing a timely diagnosis improves the care and wellbeing of patients and their families and reduces unnecessary healthcare spending.
Key to C4R-SOLVE’s success will be new sequencing technologies and improved worldwide data sharing. In addition, the group will work with provincial ministries of health to determine how best to include genomic sequencing as a clinical test to diagnose rare diseases, beginning with Alberta and Ontario. In doing so, C4R-SOLVE will more than double our ability to diagnose unsolved rare disease, while building the infrastructure and tools needed to improve rare disease diagnosis worldwide. Accurate and early diagnosis will optimize care, improve the wellbeing of patients and their families, provide new insights into these devastating diseases, and potentially save at least $28 million/year in health-care spending.
PEGASUS-2: Personalized Genomics for Prenatal Abnormalities Screening Using Maternal Blood: Towards first tier screening and beyond
Project leaders: François Rousseau (Université Laval), Sylvie Langlois (University of British Columbia)
Lead Genome Centres: Génome Québec (administrative lead), Genome British Columbia
Total funding: $12.2 million
The discovery that fetal DNA is present in the mother’s blood during pregnancy has led to the development of a genomics-based maternal blood test called NIPS (non-invasive prenatal screening), which is a very reliable test for Down syndrome. In part due to its cost, NIPS is currently only used as a second-tier test, after a mother has tested positive on less costly and less accurate tests, to confirm the finding prior to resorting to amniocentesis.
Making NIPS the entry-level test for Down syndrome could benefit women by more accurately detecting an affected pregnancy with less chance of a false positive result and by providing that result several weeks earlier in the pregnancy. As well, because NIPS can detect other chromosomal abnormalities, its use could enable screening for more conditions. The PEGASUS-2 project’s goal is to provide high-quality evidence to support the use of NIPS instead of traditional screening tests by comparing its use as a firsttier and second-tier test in a large cohort of pregnant women. The project will also study the cost effectiveness of expanding screening to other conditions and the ethical, social and legal implications of doing so. It will also provide strategies to promote shared decision-making between couples and healthcare professionals. Finally, it will further develop the NIPS technology to reduce its costs by 50 percent and expand its ability to detect other anomalies, as well as ensuring quality control for clinical NIPS testing in Canada and worldwide.
PEGASUS-2 will enable publicly funded access to a promising genomics technology for all interested pregnant women, while ensuring that couples have access to web-based tools to help their decisionmaking and that all health-care professionals are trained in shared decision-making for prenatal screening.
Genomics Technology Platforms 2016 Competition for Operations Support and Technology Development Funds
The genomics technology platforms funding funding will enable the platforms to develop new and improved genomics technologies, and provide researchers across Canada and internationally with access to leading-edge genomics tools, technologies and services, which improve the quality of research.
Two of the ten funded projects are led by researchers at UBC and its affiliated teaching hospitals received $20.7m in funding:
The Pan-Canadian Proteomics Centre
Platform Leaders: Christoph Borchers (University of Victoria), Leonard Foster (University of British Columbia)
Genome Centre: Genome British Columbia
Total funding: $11.1 million
The Proteomics Centre has been providing an extensive range of cutting-edge proteomics services for more than 15 years, during which time clients from across Canada and in more than 15 countries have accessed its services on a fee-for-service or collaborative basis. The Proteomics Centre is now the bestequipped proteomics research facility in Canada.
With new funding from Genome Canada, the Proteomics Centre will expand to be a truly pan-Canadian enterprise. The Centre will establish new nodes at the BC Cancer Agency and at the Toronto’s Hospital for Sick Children, as well as a new site for clinical proteomics at Montreal’s Jewish General Hospital. This new Pan-Canadian Proteomics Centre will broaden in-house technological expertise, increase the range of technologies offered, increase capacity for core service provision and build a vital network of key collaborators. It will have a greater emphasis on translation of technologies into real-world applications and tighten linkages to clinical facilities. It has secured more than 60 projects, worth more than $7.8 million, for 2017-2022. It will develop and implement more than 1,400 new assays, extend or add value to 20 existing services, translate 150 assays into clinical settings, introduce 20 new crosslinkers, launch 11 new software tools and venture into new technology development areas, including proteogenomics.
BC Cancer Agency Genome Sciences Centre Genomics Technology Platform
Platform leaders: Marco Marra, Steven Jones (BC Cancer Agency and University of British Columbia) Corey Nislow, Martin Hirst (University of British Columbia)
Genome Centre: Genome British Columbia
Total funding: $9.6 million
The sequencing and bioinformatics analysis platforms at Canada’s Michael Smith Genomic Sciences Centre have operated as a Genome Canada platform since 2001. In that time, its technical ability to deliver successful collaborations and service arrangements has led to its involvement in 705 grants and contracts totaling more than $875 million, and supporting the work of more than 1,500 researchers, both nationally and internationally. Among its contributions are reference genomes for bovine, spruce, poplar, Atlantic salmon and Chardonnay grape; human reference epigenomes; and human, mouse and zebrafish cDNA reference transcriptomes. Its whole-genome analysis is being used to inform personalized treatment planning for cancer patients. The platform also provides training to technical and support staff, as well as graduate and postdoctoral research trainees.
With this Genome Canada funding, the platform will expand both its personnel and its service offerings, including both new technology development and assessment and data processing and bioinformatics analysis. It will also develop a bioinformatics virtual machine to provide researchers with the computational tools they need to interact with, visualize and analyze data. This funding will also enable the GSC to grow its capacity for genomics services through the collaborative partnership with University of British Columbia.