Stephen Scherer

Personal Genome Project shows whole genome sequencing may transform how Canadians manage their own health care

noreen.rasbach — Mon, 05 Feb 2018 15:57:20 +0000

Personal Genome Project shows whole genome sequencing may transform how Canadians manage their own health care

noreen.rasbach Mon, 02/05/2018 - 10:57

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“Though we’ve identified clinically relevant genomic information for all participants, each of their genomes has even more information that we can’t interpret yet,” says Stephen Scherer, director of 91�Թ�'s McLaughlin Centre (photo by J.P. Moczulski)

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Faculty of Medicine

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McLaughlin Centre

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Stephen Scherer

Researchers from the 91�Թ� and the Hospital for Sick Children (SickKids) behind the Personal Genome Project Canada are predicting that whole genome sequencing will likely become part of mainstream health care in the foreseeable future.

In the first-ever study from the Personal Genome Project Canada (PGP-C), the researchers found 25 per cent of participants to date had genomic information indicating they could be at risk for future disease and even more were found to have genetic variants that would be relevant for family planning or newborn screening. All participants had genomic information associated with risks for adverse drug reactions or altered drug effectiveness, with 23 per cent of participants identified as being at risk for severe, potentially life-threatening adverse drug reactions.

The study was published Feb. 3 online in CMAJ (the Canadian Medical Association Journal).

PGP-C is a comprehensive public data resource that integrates participants’ whole genome sequencing data with their health information to advance scientific understanding of genetic and environmental contributions to human health and disease. All of the project’s inaugural 56 participants have clinically relevant information in their genomes, highlighting the potential of using whole genome sequencing data proactively for precision medicine and to reduce the risk of therapeutic failure.

“Though we’ve identified clinically relevant genomic information for all participants, each of their genomes has even more information that we can’t interpret yet,” says Stephen Scherer, director of 91�Թ�'s McLaughlin Centre and senior scientist and director of The Centre for Applied Genomics (TCAG) at SickKids.

Read an article in the Globe and Mail about the study and Personal Genome Project Canada

“As we analyze more samples, we continuously learn more about the human genome which will allow us to eventually take full advantage of the wealth of information it contains. That’s why the goal of the project is to sequence thousands of genomes each year.”

PGP-C is the Canadian arm of the global Personal Genome Project, a collaborative academic research effort that started with Harvard Medical School’s Personal Genome Project in 2005. A priority of the Personal Genome Project is to share information collected from the localized projects with researchers around the world to drive new knowledge about human biology.

Participants were required to undergo an extensive consent process as all data, including results from their whole genome sequencing, combined with personal and family history, is available online. Each participant had access to genetic counselling to appropriately contextualize the results of their genetic testing.

“Genetic counsellors play an important role in communicating and interpreting these results appropriately,” said Professor Trevor Young, dean of 91�Թ�'s Faculty of Medicine, which runs Ontario’s only academic training program for genetic counselling. “The demand for these specialized skills is only going to rise given the massive increase in the number of genome-wide tests now being used in hospitals.”

Interested in publicly funded research in Canada? Learn more at 91�Թ�’s #supportthereport advocacy campaign

The cost of whole genome sequencing has fallen dramatically since PGP-C began recruiting and analyzing samples in 2012 and further still from when the project was conceptualized in 2007. Signs indicate the technology will continue to become more affordable and accessible, which the authors expect will transform whole genome sequencing into more of a mainstream practice for the general population. As a result, frontline health-care providers may become involved in interpreting and delivering resulting genomic information in the near future.

The work was funded by the 91�Թ�’s McLaughlin Centre, the Canada Foundation for Innovation, Genome Canada-Ontario Genomics, the Government of Ontario, the Canadian Institutes of Health Research (CIHR), Medcan Health Management Inc. and SickKids Foundation.

Read the full study in CMAJ

Happy 150th, Canada! 91�Թ� researchers sequence the beaver's genome

ullahnor — Fri, 13 Jan 2017 17:06:47 +0000

Happy 150th, Canada! 91�Թ� researchers sequence the beaver's genome

ullahnor Fri, 01/13/2017 - 12:06

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In honour of Canada's 150th anniversary, 91�Թ� Professor Stephen Scherer and his team have sequenced a beaver

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Stephen Scherer: “This is the most important animal in Canadian history.”

They were diligent, methodical, meticulous.

They overcame obstacles large and small and applied available resources to try to achieve an ambitious goal. When they needed to move beyond existing resources, they pushed the limits and modified them. Channelling some of the most distinctive traits of the quintessentially Canadian symbol they were studying, a team of Canadian scientists has made an indelible mark on the history of this country – and beyond – just in time to kick off the country’s 150th anniversary.

The 91�Թ�'s Professor Stephen Scherer and his team of researchers from The Centre for Applied Genomics (TCAG) at The Hospital for Sick Children (SickKids) have successfully sequenced the genome of Castor canadensis – the Canadian beaver. The beaver in question is none other than Ward, a 10-year-old resident of the Toronto Zoo. The research, which will be published in the online edition of G3: Genes|Genomes|Genetics, is a partnership with 91�Թ�, Ontario Institute for Cancer Research (OICR), the Royal Ontario Museum (ROM) and the Toronto Zoo.

The study’s senior and lead authors, Scherer and 91�Թ� alumnus Dr. Si Lok, talk below about why their world-leading research team undertook this unusual project, and how understanding Ward could help scientists advance research into human conditions like autism.

Scherer is director of the McLaughlin Centre and professor in the department of molecular genetics at the 91�Թ�'s Faculty of Medicine. He is also director of TCAG, senior scientist at SickKids and is known for his work on the genetic underpinnings of autism spectrum disorder.

Lok is senior project manager and lead in technology development at TCAG. The study was supported by Genome Canada, Ontario Genomics, Canada Foundation for Innovation, the Government of Ontario, the Lau Family Endowment and SickKids Foundation.

Why did you choose to study the beaver?

Stephen Scherer: We could have done this genome research project using DNA from any human or from someone with one of the conditions we study like autism – but by going this route there was even more potential for broader impact! We started exploring our options and realized that our national symbol, the beaver, had not been sequenced yet. This is the most important animal in Canadian history, so to know about its genome allows us to better understand how it all came about: its history, how it relates to its environment. The genome is a starting point.

What’s the connection between sequencing a beaver’s genome and helping families understand why autism may affect one child in the family but not another?

Stephen Scherer: There are some families who we know have autism or some other developmental disorder because of the genetics, but we haven’t found the genetic alteration yet. The novel genome-assembly approach that we’ve developed for the beaver project will provide another vantage point.

Si Lok: The Human Genome Project led many people to think genetic sequencing is a done deal, but it’s really not. What’s typically done is genome ‘re-sequencing.’ The genomes of only a small number of people are actually fully sequenced – less than a dozen in the world. For all the others, to make it cost-effective, we quickly sequence billions of fragments but align them by comparison to a reference genome. It’s really a comparative approach analogous to tracing a picture. But ultimately, we can’t just look at the tracings. We need to see all the underlying unique pieces too, and there are lots of them.

The sequencing of Ward’s genome was done the way we’d eventually like to do everyone’s – it’s called de novo sequencing. It’s a completely original process, which allowed us to build Ward’s unique genome from the ground up so we would not use any preconception of another genome.

Stephen Scherer: Our new genome-assembly technique allows us to find new types of genetic variations we haven’t seen before using the current technologies so we think our yield in explaining autism will go up. We are already applying the technique in our human sequencing projects, as well as for other animals. It’s very exciting.

Why is the method so important?

Stephen Scherer: At TCAG, we’re generating a genome product that is really, really good, but it’s not perfect. To find all the genetic variants we need to fully understand things like cancer or autism, we needed a much better approach.

We were able to take samples from the beaver, find the DNA and put it into the latest genome-sequencing machines, which generated the three billion chemical letters of information that comprise the beaver genome. What’s unique about the project is we had to develop some new methods to actually stitch together all of those three billion chemical letters of information into a complete ‘jigsaw puzzle.’ At the end of the day, we were able to generate the complete genome sequence of what we believe is the most important animal in Canada.

With new technologies and new sets of analytical experiments we’ve developed here, we can now apply what we learned in the beaver-sequencing project to those human disease projects we are doing here at the same time.

What does this study show us about the beaver?

Stephen Scherer: What we found is that the beaver genome is roughly the same size as the human genome, maybe a little smaller. That’s not really surprising to us. If you look at any mammalian genome sequence – mouse, rat, chimpanzee – and compare it to humans, they’re roughly the same size.

We were able to clearly describe the genes that are important to rodents and most importantly to the beaver. We identified the genes involved in dentition and enamel deposition, a defining characteristic of rodents and particularly of beavers. Rodents are classified by their teeth structure, and beavers seem to take this to the extreme because their teeth continuously grow so they can chop down trees. They incorporate a special kind of enamel to strengthen the teeth and iron to sharpen them. The mechanism resembles a self-sharpening ice skate, which gets sharper as you skate.

This is really about the power of genetics. We’ve never sequenced any genomes with the quality that we’ve had with the beaver. It’s exciting because it allows us to see some things for the very first time.

Why did you do it now?

Stephen Scherer: Lok and I went to graduate school and did our PhDs at SickKids under Professor Lap-Chee Tsui, the world-famous Canadian geneticist who discovered the cystic fibrosis gene in 1989. As Canadians, we wanted to give back in some way, above and beyond our typical research.

We recognized that the coming sesquicentennial of Canada, new technologies, and our ideas provided the ‘perfect storm’ for us to make a lasting contribution to the scientific world, to our future research and to the sense of Canadian characteristics of hard work, loyalty, and pride in our heritage.

André Picard to biomedical researchers: do a better job of making your case

krisha — Fri, 16 Sep 2016 18:36:18 +0000

André Picard to biomedical researchers: do a better job of making your case

krisha Fri, 09/16/2016 - 14:36

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(Photo by Horst Herget Photography)

Carolyn Morris

Author legacy

Carolyn Morris

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“Too much of what you do is a mystery to people,” The Globe and Mail's public health reporter André Picard told an audience of 91�Թ� scientists.

“You can’t expect people to embrace the notion that investing in biomedical research is a good thing, if they don’t see the practical outcomes of research in their everyday lives.”

At a dinner celebrating the 25th anniversary of the department of biochemistry’s George Connell Lectureship, Picard spoke about the future of biomedical research in Canada, Recognizing the increased difficulties in securing research funding, he admitted he might not provide any satisfactory answers.

“In journalism we specialize at shining the light on problems and don’t do anything about solutions, unfortunately.”

But Picard emphasized the importance of communicating the value of science and criticized what he sees as the increasingly partisan and industry-focused nature of government investment in science.

“The greatest innovations in science are almost always through serendipity,” he said. “We need to create an environment in which ideas can flourish — to give scientists the time and the money to study problems, and the freedom to find solutions.”

This realm of ideas and problem-solving was on display at the George Connell Lectureship — a tribute to the esteemed biochemistry professor and former 91�Թ� president, who made countless contributions to science, both as a researcher and as an administrator. Professor Connell died in 2015.

The 2016 Connell Lecturer was Molecular Genetics Professor Stephen Scherer, who delved into the genetics and molecular imbalances in autism and related disorders. This cross-fertilization reflects an increasing focus on scientific collaboration that reaches beyond departmental boundaries.

“Nothing would please George more than these fascinating lectures,” said Sheila Connell, the wife of late Professor George Connell. Much of Professor Connell’s family attended the event — including three of his children, Thomas, Caroline, and Meg, as well as members of their families.

“He was a fundamental scientist at the leading edge of the field, and his work is still cited to this day,” said Biochemistry Department Chair Justin Nodwell. “As the linchpin event of this department, this is a fitting tribute to Dr. Connell.”

Balancing out the worrying trends in biomedical research described by Picard, Nodwell spoke optimistically about how scientists from biochemistry, molecular genetics and laboratory medicine and pathobiology are preparing to move into a new collaborative and open-concept research space in the West Tower of MaRS this fall.

“Countless big discoveries have come from the interfaces between disciplines,” he said. “We’re bringing together top minds in infectious diseases on one floor and in genetic models of disease on another. While we’ve been working together over the past years, this is the first time we’ll be interacting with such high frequency.”

And perhaps this increased integration will serve to find answers, and to demonstrate just how valuable biomedical research is to society.

91�Թ� to sequence genomes of 10,000 people per year: “Information is the new oil,” say 91�Թ� scientists

lanthierj — Wed, 14 Sep 2016 19:52:23 +0000

91�Թ� to sequence genomes of 10,000 people per year: “Information is the new oil,” say 91�Թ� scientists

lanthierj Wed, 09/14/2016 - 15:52

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(all photos by Johnny Guatto)

Heidi Singer

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Heidi Singer

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City & Culture

Hospital for Sick Children

Research & Innovation

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City becomes one of the world’s leading producers of biodata

The 91�Թ� today launched a massive project to sequence the whole genomes of 10,000 people per year – positioning Toronto as a leader in the global race to understand complex diseases.

With the population of Toronto among the most diverse in the world, the project will provide an unusual breadth of genetic material to study, said Professor Stephen Scherer, director of 91�Թ�’s McLaughlin Centre and the Centre for Applied Genomics at The Hospital for Sick Children (SickKids).

He said the move will accelerate the big data revolution and create a new generation of precision therapies.

“With sequencing now married to large-scale computation, I believe we in Toronto can help lead the way for precision medicine. Genomic information is the new oil. It’s the resource that’s going to drive technology in the new era.

“We’re generating the oil that researchers will use to enable discoveries and to create new products in software, biotechnology and information management that will realize precision medicine.”

Stephen Scherer

Personal Genome Project shows whole genome sequencing may transform how Canadians manage their own health care

Read an article in the Globe and Mail about the study and Personal Genome Project Canada

Interested in publicly funded research in Canada? Learn more at 91�Թ�’s #supportthereport advocacy campaign

Read the full study in CMAJ

Happy 150th, Canada! 91�Թ� researchers sequence the beaver's genome

André Picard to biomedical researchers: do a better job of making your case

91�Թ� to sequence genomes of 10,000 people per year: “Information is the new oil,” say 91�Թ� scientists

Read more about Scherer's research