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Leveraging Big Data to drive cancer innovations

We asked Dr. Mélanie Courtot about her research interests and her new role as OICR’s Director of Genome Informatics.

OICR-supported projects generate huge amounts of genomics data that have the potential to inform major innovations in the detection, diagnosis and treatment of cancer. But to have an impact, those data need to be accessible to the many researchers investigating why and how cancer develops.

Dr. Mélanie Courtot joined OICR in January 2022 as Director of Genome Informatics and incoming Principal Investigator, bringing a passion for building intelligent data systems to help improve human health. She recently spoke to OICR News about her new role and her vision for a harmonized “knowledge ecosystem” for cancer data.

How did you first become interested in bioinformatics?

I’ve always wanted to work in the health domain. Health affects everyone, and there are so many great opportunities to make an impact. I’ve also always liked computers because they are very black and white. You input instructions and they either work, or they don’t. I’m very logical and the clear instructions and clear results with computers suit me well.

I did my bachelor studies in structural biochemistry and then earned a master’s degree in computer science in 2002. At the time, the Human Genome Project was all over the news and bioinformatics was quite trendy. I saw that it was a discipline that could bring together two domains I liked: health and computing. It was a natural fit, and so I began working as a software engineer and consultant in the bioinformatics space and ended up doing a PhD in bioinformatics at The University of British Columbia.

After several years at the European Bioinformatics Institute, you joined OICR as Director of Genome Informatics in January. Tell us about that role.

I lead the Genome Informatics team, which develops algorithms, software products and production systems for OICR’s Big Data platforms. OICR and our supported programs are collecting more and more genomics data, and we want that data to be useful to other researchers. So we need to make the data sets accessible, and integrate them in a way that researchers can find them and use them to build their own research studies and test their own hypotheses. We also maintain a large data processing centre, which addresses a lot of issues around scalability and the size of data sets.

What made you want to work at OICR?

The team at OICR has an excellent reputation, so that attracted me. I’m also really looking forward to collaborating closely with other teams and programs at OICR that are leveraging the data downstream. It’s great to create data platforms, but in the past, I was a bit further away from the application side. I am excited to have a closer connection with the researchers using the data because it’s the users who should drive the type of data we collect and how it should be annotated and made accessible. Working closely with them will help improve processes on both sides, and I look forward to helping the data drive innovations in other programs.

You are also an incoming Principal Investigator at OICR. What are your research interests?

My research is around data quality, data integration and data availability. I’m really interested in how we handle and integrate Big Data in disparate data sets. In the health domain, everybody is generating their own data in their own ways, and it comes from many different places — from hospital data to research institutions to patient registries. There is so much data in so many places, and if they’re not linked or harmonized, the right data can be hard to find, tough to access and too heterogenous to use efficiently.

My research is about finding ways to improve how data sets are stored, processed and linked so they can be reused by scientists to make important discoveries. My dream is to create a knowledge ecosystem for health data that informs cancer detection, diagnosis and treatment.

What is the potential of harnessing all this data?

If researchers can effectively access and use the data, they can explore the relationship between different data attributes and potentially identify biomarkers that help determine if cancer is likely to develop and — if it does — how best to treat it. Providing this precision care will increase people’s chance of surviving cancer.

For example, imagine going to a clinic for your annual health checkup. They draw some blood and run a panel of diagnostic assays. They refer to your family history and your DNA sequence and ask some questions about your lifestyle. And based on this data, they find that you have an increased risk of developing cancer in the next five years. With that knowledge, you can be monitored more closely to ensure that if cancer develops, it is caught as early as possible and can be treated in a way that is tailored to your specific health needs. This also benefits the health system, because treating cancer earlier is less complicated and less costly. 

That’s my vision: transform healthcare by integrating genomics, lifestyle and environmental data to better understand, detect and treat cancer. 

OICR announces funding for three new window-of-opportunity clinical trials

Trials are part of OICR’s Window-of-Opportunity Network

June 16, 2022  — Toronto — The Ontario Institute for Cancer Research (OICR) is announcing funding for three new Ontario-based clinical trials as part of its Window-of-Opportunity (WOO) Network.

A collaboration between OICR and Ontario’s research community, the WOO Network supports clinical trials that focus on understanding tumour biology in newly diagnosed or newly recurrent cancer patients. These trials will help scientists understand the impact of cancer therapeutics before surgery, with the goal of helping to improve treatment options for future generations of cancer patients.

The WOO Network is proud to support: 

  • Dr. Michael Ong at the The Ottawa Hospital is examining the effectiveness of pre-operative radiotherapy combined with immunotherapy in patients with bladder cancer, with a specific focus on the role of radiotherapy in ‘priming’ a patient’s immune system to enhance cancer immunotherapy. 
  • Dr. Malcolm Moore and a team from Princess Margaret Cancer Centre, The Ottawa Hospital and Juravinski Cancer Centre are exploring the effect of combining two immunotherapy drugs (durvalumab and oleclumab) given prior to surgery, on the tumour stroma and immune function of patients with resectable pancreatic cancer.
  • Dr. Dan Breadner of the Baker Centre for Pancreatic Cancer and Lawson Health Research Institute (London Health Sciences Centre) and the Schulich School of Medicine & Dentistry (Western University) is examining if stereotactic ablative radiation (SABR) therapy can reduce the size of pancreatic tumours and make surgeries more effective, while also monitoring for immune changes in and around the tumour that may increase the chance that a patient’s tumour responds to chemotherapy or immunotherapy.

The ‘window-of-opportunity’ is the two-to-six week period between when a person receives a cancer diagnosis and their scheduled surgery. Being able to study cancers before surgery may provide insights into new ways to identify cancer, to measure how cancer cells respond to treatment and to understand how a new therapy works. In particular, window-of-opportunity trials may provide insight into new possible neo-adjuvant therapies aimed at eradicating diagnosed cancer before surgery.

Support for window-of-opportunity trials is part of OICR’s Strategic Plan for 2021-2026, which has a focus on advancing early detection and intervention research, reinforcing Ontario’s global leadership in data sharing and analytics, expanding on Ontario’s robust pipeline of novel cancer therapies and then helping navigate those therapies into commercialization and clinical use.

For more information or to book an interview, contact:

Daniel Punch
Senior Communications Officer, OICR
daniel.punch@oicr.on.ca
647-291-4583

Perspectives

“These innovative trials will provide a unique window into our understanding of cancer biology in response to treatment. We’re excited to collaborate with three outstanding research teams.”
– Dr. Melanie Spears, WOO Network Co-lead, Principal Research Scientist at OICR

“The opportunity to initiate potential cancer therapies before surgery will give us a greater understanding of which treatments work best for which patients, and ultimately help bring the most effective therapies to the people who need them.“
– Dr. Angel Arnaout, WOO Network Co-lead, Surgical Oncologist and Professor of Surgery at the University of Ottawa

“The authentic involvement of patient partners is one of the WOO Network’s many strengths, and I know these exciting trials will benefit from the perspectives that we as patient partners are able to offer.”
– Carol Gordon, Patient Partner, Member of OICR’s Patient and Family Advisory Council

“Collaborating with OICR has allowed us to move forward with a study we hope can help bring about the best outcomes for people with bladder cancer with the least amount of side effects.“
– Dr. Michael Ong, The Ottawa Hospital

“The WOO Network has helped set our trial up for success as we explore the genetics of pancreatic tumours and how they respond to a combination of immunotherapy medications.“
-Dr. Malcolm Moore, The Princess Margaret Cancer Centre and Drug Development Program

“Our team is excited to better understand the impact of stereotactic ablative radiation (SABR) on pancreatic cancer, and we are grateful to OICR for all its support through the WOO Network.“
– Dr. Dan Breadner, Baker Centre for Pancreatic Cancer

“WOO trials are fantastic collaborations between OICR, cancer researchers from various disciplines and people with cancer from across Ontario that will fuel innovations that improve health outcomes in Ontario and around the world.“
– Dr. Laszlo Radvanyi, President and Scientific Director, OICR


About OICR

OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit http://www.oicr.on.ca.


The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

Beyond ‘impact factor’: OICR signs DORA declaration for more equitable research assessment

The Declaration on Research Assessment (DORA) calls for fairer ways to evaluate researchers and scholarly outputs.

Scientific contributions come in many forms and from many places, and not all end up in the pages of prestigious academic journals.

Yet researchers are often funded, hired and promoted based on whether they publish in journals that score high on Journal Impact Factor, an imperfect measure of a journal’s quality.

A growing segment of the research community argues that relying on metrics like Journal Impact Factor paints an incomplete picture of scholarly impact and risks leaving some researchers behind. More than 21,000 researchers and organizations from 158 countries have signed The Declaration on Research Assessment (DORA), which seeks to improve how research is evaluated, and now OICR is among them.

“OICR signed DORA because we support the principles behind it, including assessing research on its own merits and considering broader ways to measure impact,” says Rebecca Tamarchak, Senior Director of Strategy and Governance at OICR.

The DORA declaration recommends eliminating the use of journal-based metrics when evaluating research, and judging papers on their scientific content instead of where they are published. DORA suggests that institutions have clear criteria for hiring and promotion decisions that look beyond publication metrics, especially in the case of early career researchers.

The declaration also recommends institutions capitalize on new opportunities created by online publishing, and explore ways to measure other forms of impact, including influence on policy and practice.

Tamarchak says these recommendations are very consistent with OICR’s current measures of research impact, but OICR is always aiming to improve its processes.

“We are evaluating our current funding guidelines and processes to ensure we are implementing best practices in alignment with DORA,” she says.

Find out more about the DORA declaration.

New ICGC DACO website offers improved access to cancer data

A new online data access application will provide cancer researchers with a more streamlined and secure way to access important information about tumour mutations.

On May 16, the International Cancer Genome Consortium (ICGC) Data Access Compliance Office (DACO) launched a new website that gives researchers access to ICGC’s controlled data sets.

ICGC’s catalogue of tumour-specific data is freely available to the scientific community, offering key insights into cancer biomarkers that can inform the next generation of diagnostics and therapies. But to minimize the risk of identifying donors, ICGC DACO developed a simple yet secure authorization process for research teams wanting to access the data.

The new site replaces the original ICGC DACO website, an innovative data access application that has been harnessed by about 1,500 researchers since it launched in 2011.

The redesigned website offers better usability, including an improved application form that guides applicants through the process. Under a new data access agreement, the revamped site allows researchers to be approved for two years of access to IGCC controlled data, instead of just one year under the legacy system.

Data security is paramount in the new website, which offers even stronger security to ensure that only known, authorized users can access the data sets. New security features include a single sign-on identification system through Google based authentication.

The legacy ICGC DACO website has now been retired, so approved research teams are strongly encouraged to copy over the relevant information from their legacy application to a new application in the new website.

“We are proud to offer a more streamlined website that is easier to manage and reduces the risk of data loss,” says Kim Cullion, Senior UX/UI Designer for OICR’s Genome Informatics team. “We thank our talented team of engineers, architects and everyone who contributed to the project, and are excited for the first batch of applications to be approved soon.”

Visit the new ICGC DACO website at daco.icgc-argo.org

OICR launches new Patient Partnership Plan

OICR has taken a major step to integrate patient perspectives across its research programs by launching a new Patient Partnership Plan.

Co-created with the OICR Patient and Family Advisory Council (PFAC), the Patient Partnership Plan will guide OICR’s activities over the coming three years to ensure they benefit from the lived experience of cancer patients and their families.

OICR believes partnering closely with patients will help align research priorities with patient needs, strengthen cancer research in Ontario and ultimately improve cancer care.

The new Plan establishes several goals for involving patients in research and sets out activities to achieve them. These activities are underpinned by three priorities:

  • Bringing the patient voice to OICR research
  • Building capacity for patient partnership
  • Sharing knowledge

Launching the Plan marks the next stage in OICR’s work to put patients at the centre of its research programs. OICR launched the PFAC in early 2021 and has since incorporated patients into its funding review process, supported research teams to form patient partnership plans and embedded patient partners in key advisory roles.

Moving forward, OICR will evaluate its progress toward the Plan’s objectives and use what it learns to strengthen patient partnership activities.

OICR thanks members of the PFAC for their contributions to the Plan and acknowledges founding PFAC chair Antonia Palmer for working with OICR to initiate these activities. Antonia recently stepped down from her role and OICR welcomed Diana Lemaire as new PFAC chair.

See our Patient Partnership Plan

Perspectives

“OICR PFAC members and staff have undertaken a thoughtful and collaborative process to develop our first Patient Partnership Plan. The PFAC is excited to work with staff and researchers to make patient partnership integral to OICR as we move cancer research forward together.”
Diana Lemaire, OICR Patient and Family Advisory Council Chair

“This plan is the culmination of so much hard work from dedicated patient partners and OICR staff. Yet it’s also a new beginning, and I’m excited to see the impact patient perspectives will have on the future of cancer care in Ontario.”  
Rebecca Tamarchak, OICR Senior Director, Strategy and Governance

“Working closely with patient partners has been a tremendous learning experience for everyone at OICR. Their insights have shaped our research for the better, and we look forward to continuing our partnership to solve cancer together. I would like to thank our PFAC and all our patient partners for their time and dedication in working with us to strengthen OICR’s impact.”
Dr. Laszlo Radvanyi, OICR President and Scientific Director

Innovative MRI shines new light on cancer

Synthetic correlated diffusion imaging detects tumours and their margins by capturing the movement of water through tissue.

Cancer can be tough to distinguish from the healthy tissue around it, especially in the black-and-white image from a standard MRI.

But new MRI technology is harnessing one of cancer’s unique properties — its irregular density — to ‘light up’ cancerous tissue and pinpoint where it is located.

Synthetic correlated diffusion imaging uses MRI signals and a sophisticated algorithm to capture how water molecules move through tissue at different levels. Cancer cells are packed less uniformly than other tissues, and so the irregular movement of water indicates the presence of cancer.

The system generates an image that resembles a heat map — the more intense the irregular movement of water in one area, the brighter it appears. Cancerous tissue shows up as bright red spots, which researcher Dr. Alexander Wong says makes it easier to see tumours among the surrounding tissue.

“By having the tumour light up in red, we can better localize and detect it, and also get a clearer picture of the margins around it,” says Dr. Wong, an OICR Affiliate and Canada Research Chair in Artificial Intelligence and Medical Imaging at the University of Waterloo.

Dr. Alexander Wong

Dr. Wong and his colleagues spent six years developing synthetic correlated diffusion imaging, hoping to create a cancer-targeted alternative to the standard MRI, which produces images where cancer can be difficult to see.

In addition to Dr. Wong, Dr. Masoom Haider, Professor of Radiology at the University of Toronto and an OICR Clinician Scientist, and University of Waterloo graduate students Hayden Gunraj and Vignesh Sivan, were the core members of the research team. They collaborated with experts at OICR and multiple Toronto hospitals.

Their preliminary study was published in Scientific Reports and describes how synthetic correlated diffusion imaging accurately detected tumours and their margins in 200 patients with prostate cancer. They are also conducting another study testing their new MRI system with breast cancer patients, and Dr. Wong says results are similarly promising.

These studies show that synthetic correlated diffusion imaging has the potential to strengthen early detection, which is crucial to surviving both prostate cancer and breast cancer. It could also help track tumour growth and inform more precise surgeries and therapies.

“I can see a lot of different areas where this could be really important,” Dr. Wong says. “It could help a lot of people get earlier treatment as well as more personalized, targeted treatment.”

Encouraged by the positive results, Dr. Wong says the research team hopes to do a much larger study to refine and validate their technology. They are also exploring how to best integrate synthetic correlated diffusion imaging into clinical practice.

Because it uses the same technology as standard MRI, but with different pulse sequences and specialized software to process data, integration could be relatively seamless.

“That’s the beauty — the physical piece of hardware doesn’t change,” says Dr. Wong. “We designed it so that it can easily fit within the imaging workflow.”

He says it’s also important that results are delivered in a way that resonates with clinicians and helps them make informed care decisions.

“At the end of the day, this is a tool,” Dr. Wong says. “It needs to be something that clinicians can effectively leverage in order to have an impact on what matters most: the health and wellness of patients.”

New research asks if clinical trials are losing sight of what matters most to cancer patients

Dr. Bishal Gyawali says research into new cancer drugs should focus on outcomes like quality of life and overall survival.

Cancer therapies should help people live longer or live better, and ideally they should do both.

“That’s just common sense,” says medical oncologist Dr. Bishal Gyawali.

But Dr. Gyawali’s research shows that clinical trials for new cancer drugs don’t always prioritize outcomes like quality of life and overall survival. And he worries oncology is losing sight of what matters most to cancer patients.

“What patients care about is how long they’ll live and how well they’ll live,” says Dr. Gyawali, an OICR Clinician Scientist and Associate Professor at Queen’s University. “But unfortunately, these outcomes are frequently not measured or even discussed in clinical trials.”

Dr. Gyawali’s latest research explores how quality-of-life outcomes are reported in clinical trials for new cancer drugs. He worked with colleagues at Queen’s University — including quality of life experts — to conduct a cohort study of recent Phase III trials and published their findings in JAMA Oncology.

To start, they had to exclude a large proportion of trials because the papers didn’t report on quality of life at all. Of studies that did, less than a quarter of therapies actually improved patients’ quality of life. That wasn’t surprising to Dr. Gyawali, who found in a 2018 study that just 42 per cent of cancer clinical trials reported on quality-of-life outcomes, and ones that did mostly reported no improvement.

What surprised Dr. Gyawali in his new study was that when drugs failed to improve quality of life, results were often presented with a favourable spin. Unchanged quality of life was described as “maintained” or “not worsened” in some journal articles, while decreases in quality of life were sometimes written off as “not clinically significant.”

“A patient wants their quality of life to improve,” Dr. Gyawali says. “How can I tell a patient that if you take this drug your quality of life will ‘not be worse?’”

Instead of focusing on quality-of-life outcomes, many studies reported on progression-free survival (PFS), a measure of how much tumours grow or shrink over a period of time. But Dr. Gyawali and colleagues found that improvements in PFS were not necessarily associated with improvements in quality of life. In fact, some cancer therapies that slowed the growth of tumours actually made patients’ quality of life worse and had no effect on how long they survived. Yet, these trials were still framed as successful.

Dr. Gyawali says that raises major questions about the value of PFS as an endpoint. “If a drug delays the growth of the tumour but does not improve survival and worsens quality of life, then we should call that drug harmful,” Dr. Gyawali says.

The JAMA Oncology study reinforces much of Dr. Gyawali’s recent work, which has taken a hard look at oncology research in the hopes of making it more patient-centred.

His interest in this area began shortly after he became a medical oncologist in 2017. He says his medical education in Nepal focused mainly on “textbook medicine,” and he didn’t initially question the evidence behind his textbooks. But studying oncology in Japan opened his eyes to evidence-based medicine, and he started digging deeper into the clinical trials underlying the drugs he was supposed to prescribe.

He says he found flaws in how some trials were structured and reported, which led to expensive cancer drugs that offered little benefit to patients being approved and prescribed. “It was like an epiphany when I first noticed this,” he says. “Then I started seeing it everywhere, and it became my major research theme.”

He approaches this research from various angles, looking at medical education, research processes and policy decisions to see why oncology research can sometimes “forget the bigger picture” of its impact on patients.

And this April, he and his Queen’s University collaborator Dr. Christopher Booth described some overarching problems in a Nature Medicine paper titled “Cancer treatments should benefit patients: a common-sense revolution in oncology.”

“Our overall theme is that cancer treatments should benefit patients and we’re losing sight of that,” Dr. Gyawali says. “So how can we bring the system back in line with what matters to patients?”

Among many recommendations, Drs. Gyawali and Booth suggest changes to medical education to improve doctors’ ability to critically assess literature, changes to clinical trials to focus more on patient-centred outcomes like quality of life and overall survival, and changes to the journal publishing process to ensure that studies are reported without hype or bias.

These and other changes could help ensure oncology is focused on what’s most important, Dr. Gyawali says, and make sure patients and their doctors have the best information to make decisions about their health. “I want a society where patients are more and more aware of these issues,” he says. “Their lives and well-being are literally at stake.”

Dr. Gyawali knows his research is sometimes seen as controversial, and says he gets mixed reactions from colleagues when his papers are published. But he doesn’t think it’s revolutionary to say that cancer therapies should benefit cancer patients.

“If cancer drugs can’t improve a patient’s chance of surviving or improve their quality of life, then we shouldn’t be using those drugs,” he says. “That shouldn’t be controversial.”

Building evidence for the landmark U.S. ban on menthol cigarettes

OICR Senior Investigator Dr. Geoffrey Fong’s research helped inform the newly proposed tobacco control policy.

When the U.S. Food and Drug Administration (FDA) announced in April 2022 that it was moving forward with a ban on menthol cigarettes, FDA Commissioner Dr. Robert Califf said the ban would help smokers quit, stop young people from starting smoking, and save lives.

He knows that in part because of OICR Senior Investigator Dr. Geoffrey Fong.

Dr. Fong is widely renowned for his research into the impact of policies to curb tobacco smoking — the greatest cause of preventable cancer in Ontario, in Canada and around the world. As Chief Principal Investigator of the International Tobacco Control Policy Evaluation Project (ITC Project) at the University of Waterloo, he led an evaluation of Canada’s recent menthol cigarette ban that was cited by the FDA as it explored a U.S. menthol ban.

Canada became one of the first countries to ban menthol cigarettes when all provinces introduced bans between 2015 and 2018, and then became the first country where a menthol ban has been evaluated on whether it leads smokers to quit.

Smoking kills about 45,000 Canadians every year, and public health authorities including the World Health Organization have long advocated for banning menthols, which have added flavouring and are popular among young smokers, women and some minority groups.

In their initial analysis published in April 2021, Dr. Fong and his ITC Project colleagues showed that banning menthol cigarettes made Canadian menthol smokers significantly more likely to quit than those who smoked non-menthol cigarettes. He presented these findings to colleagues at the FDA. Three weeks later, the FDA announced that it would develop a rule to ban menthol, citing the ITC study.

Now, on the same week of the FDA’s latest announcement, Dr. Fong and colleagues published a new analysis in Tobacco Control that projects the U.S. ban could lead 1.3 million American smokers to quit.

“This is an enormous, landmark decision by the FDA,” says Dr. Fong, who spoke about the decision with several major U.S. news outlets including the New York Times, Washington Post and NBC News. “It’s a major step in tackling the number one preventable cause of cancer and non-communicable diseases.”

This newest study builds on the ITC Project’s previous work by combining ITC data across 7 provinces with data from another project that also evaluated the impact of the menthol ban only in Ontario. Together, they found that 22.3 per cent of menthol smokers quit following the ban, compared to 15 per cent of non-menthol smokers. Applying that 7.3 per cent difference to the more than 18 million menthol smokers in the U.S. gave Dr. Fong and colleagues their 1.3 million estimate.

The menthol ban is likely to have a major impact on the health of Black Americans, who smoke menthols at much higher rates than other Americans and who have been targeted by aggressive menthol tobacco marketing. Dr. Fong’s research estimates that more than 381,000 Black smokers are likely to quit following the ban.

Although the policy has been formally proposed, it may take years before a ban comes into force. The proposal still needs to be finalized and will likely face strong pushback from tobacco companies.

The tobacco industry has a long history of suing countries that try to implement stronger policies, often attempting to discredit the evidence behind those policies. That’s why having comprehensive, population-level studies like Dr. Fong’s is particularly important to the success of these measures.

“Our study is the most complete evaluation of Canada’s menthol cigarette ban,” Dr. Fong said. “I think it can stand up to the challenges that will be coming.”

Predicting cancer evolution with deep learning algorithms

New proof-of-concept approach offers faster, more accurate inferences about tumour populations.

The prevalence of mutations in a tumour can provide clues about how the cancer has grown or evolved and how best to treat it.

But making predictions about the evolution of mutated tumours using a single DNA sequenced biopsy requires complex estimates, and current methods are either slow, or don’t always consider why certain subpopulations of cells proliferate more than others.  

This led a pair of researchers at the Ontario Institute for Cancer Research (OICR) to develop a new method for understanding and predicting cancer evolution that harnesses modern deep learning algorithms and incorporates evolutionary modeling.

TumE is a deep learning approach that analyzes the frequency of mutations in a biopsy — known as the variant allele frequency — to identify which subpopulation of mutated cells that are most “fit” and thus most likely to make a tumour stronger.

“We’re taking deep learning tools into the cancer genomic space and trying to find optimal methods for predicting and understanding cancer evolution,” says lead researcher Tom Ouellette, a PhD student at OICR based in Dr. Philip Awadalla’s lab.

Tom Ouellette
Tom Ouellette

TumE’s algorithm uses evolutionary modeling to distinguish between cases where highly “fit” cellular subpopulations are driving tumour growth versus cases where no one cell or subpopulation has a detectable advantage. This helps it make predictions about how many subpopulations are observed in a tumour biopsy, and which subpopulations and mutations will eventually take over.  

Understanding which mutations will increase in frequency can provide insight for therapeutic intervention or for quantifying the aggressiveness of tumour growth.

TumE builds on two other methods for inferring the evolution of mutations — approximate Bayesian computation and mixture models — which have been used for several years but have limitations. When tested with simulated data and 88 whole genome sequence samples, as reported in PLOS Computational Biology, TumE generated inferences that were faster than approximate Bayesian computation and more accurate than mixture models.

Though it’s still at the proof-of-concept stage, Ouellette says that TumE offers a good foundation for quickly understanding the link between mutations and the evolutionary dynamics that drive cancer. With access to more data, he says the approach could be scaled up to make more complex predictions.

“With high-quality data and with minimal computational cost, we could use methods like TumE to find patterns and start making statistical estimates of which mutations lead to worse outcomes,” he says.

The advantage of deep learning is that, once something like TumE has been developed, it can be re-tuned to predict different things without having to start from scratch. Eventually, Ouellette says deep learning could be used to determine which mutations or subpopulation of cells are most deadly and should be targeted with precision cancer treatments, ultimately leading to better outcomes for patients.

“We’re trying to find methods that can be used quickly and concurrently with patient care,” he says. “I think this is a stepping stone to get there.”

 TumE is publicly available for use at https://github.com/tomouellette/TumE

Two OICR innovations bolstered by investments from FACIT

Investments will support high-profile work led by Dr. Rima Al-awar and Dr. Lincoln Stein.

Groundbreaking projects in OICR’s Drug Discovery and Adaptive Oncology research themes are receiving support to advance made-in-Ontario innovations thanks to investments from FACIT.

The investments announced on April 27 will support work led by OICR’s Head of Therapeutic Innovation and Drug Discovery Dr. Rima Al-awar and Head of Adaptive Oncology Dr. Lincoln Stein.

Dr. Al-awar’s Drug Discovery team is working on a therapeutic platform that targets members of the WD40 repeat domain family of proteins, research that has garnered a lot of attention for its potential to enable new drug discoveries and intellectual property.

Dr. Stein’s team is applying deep data analytics, network association and informatics to better understand the cancer genome. Funding from FACIT will help researchers validate and optimize proprietary technology that helps prioritize tumour targets.

“Congratulations to Dr. Al-awar and Dr. Stein on receiving critical seed capital from FACIT,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Our world-leading Drug Discovery and Informatics teams are in a unique position to leverage an organic partnership and develop their integrated, competitive platform technologies.”

These new investments come through FACIT’s Prospects Oncology Fund, which provides seed-stage capital for Ontario-based innovations in oncology. FACIT’s review of Prospects Oncology Fund investments are complemented by third party expert reviews to support the best innovations in the province.

“The FACIT team is pleased to support these internationally renowned scientists and invest in product platforms with serious potential for the treatment of cancer,” FACIT President Dr. David O’Neill says.

FACIT and OICR are collaborators in translating cancer research discoveries to patients. Learn more about OICR and FACIT.