NEW YORK (GenomeWeb) – A new project that aims to develop omics-based early diagnostic tools to help tailor treatments for people with autism spectrum disorder is underway in Canada.
The Individualized Treatments for Autism Recovery using Genetic-Environment Targets (iTARGET) Consortium aims to ultimately help change clinical practice, which currently relies on behavioral analysis for diagnosis.
US-based nonprofit patient advocacy organization Autism Speaks is contributing about C$6 million (about $4.5 million) of in-kind sequencing-associated funding to the project. In addition, regional funding agency Genome BC will be contributing C$1 million (about $741,000) in cash to the effort.
The consortium is made up of several research teams looking at the microbiome, genome, metabolome, and phenotypes of more than 1,500 autism patients and their families in the first two years to find clearer links between genetic and environmental factors that contribute to ASDs.
In years three and four they plan to expand the cohort size to 4,000 individuals which will be recruited through British Columbia Children's Hospital, provincial health authorities, and the Pacific Autism Family Network hub in Richmond, BC, said Suzanne Lewis, a researcher at BCCH, vice president of research and chief medical officer for PAFN, and chair of the iTARGET project.
"We are targeting [possible] biomarkers that would be informative to treatments for autism," said Lewis, who is also a professor at the University of British Columbia. "These targets are both of a genetic and environmental focus."
iTARGET will also be collaborating with the MSSNG project, a long-running collaboration between Autism Speaks, the Hospital for Sick Children in Toronto, and Google that aims to create genomic and behavioral data resources based on whole-genome sequencing data to inform patients and their families about the role of genetics in autism.
The MSSNG project, led by Stephen Scherer, the director for the Center for Applied Genomics at the Hospital for Sick Children and the McLaughlin Center for Molecular Medicine at the University of Toronto, will provide WGS services to iTARGET, which will in turn share data with MSSNG.
Specifically, Scherer's group will be performing WGS on whole blood samples from the iTARGET cohort using the Illumina HiSeq X platform. The team will call variants for every individual based on reference WGS data available through the Center for Applied Genomics and other publicly available sources.
"Our group has spent a lot of time testing microarrays and exomes compared with whole-genome sequencing and our data now [shows that] in a research setting one should just get on with it and do whole-genome sequencing," Scherer said. "The fact that most every other site in the world is also using the Illumina X platform for WGS creates an interesting opportunity of sharing data around the world for meta-analyses, increasing the sample sizes."
Both the metabolomics and microbiomics screening is going to be streamlined through two spinout companies of the Canadian Personalized Medicine Initiative — Molecular You and an as-yet unnamed company — which will be working with a pilot proof-of-concept collection and analysis pipeline for urine and blood. This effort will be facilitated by teams led by David Wishart at the nationally funded Metabolomics Innovation Centre, Christoph Borchers at the British Columbia Proteomics Network, and Bill Mohn and Brett Finlay from Vancouver firm Microbiome Insights.
Meanwhile, Lewis will be leading efforts to complete deep phenotyping work through her lab at UBC. As data is collected it will be sent to a centralized database, currently called ASDbase, which is under development through funding by the Canadian Foundation of Innovation and in partnership with PHEMI Health Systems. The hope is that the database will be used to store and manage all of the data, including the different layers of omics information, for public use.
Autism spectrum disorders (ASDs) is the name for a group of developmental disorders which include a wide range of symptoms, skills, and levels of disability. Some form of ASD affects 1 in 68 children, according to the US Centers for Disease Control and Prevention. For these children, early diagnosis and treatment can create significantly better outcomes later in life.
Currently, the gold standard for ASD diagnosis comprises two interview and observational tests, the Autism Diagnostic Interview and the Autism Diagnostic Observation Scale/Schedule, which can be performed by a specialist. This measure makes it nearly impossible to diagnose ASDs in children younger than three or four years, Lewis explained.
"You are missing an important window of opportunity [to change] developmental trajectory," she added. "There is plenty of evidence that shows that IQ adaption and vocabulary can change for the better the earlier behavioral intervention starts."
Lewis hopes that by creating omics-based diagnostic tools, they can provide the ASD community with an early diagnostic alternative that can be used in conjunction with psychometric measures. "Those psychometric measures tell you a little bit more about the function, because they are important, but they shouldn't be used in exclusion of everything else for diagnosis."
Aside from early diagnosis, iTARGET will also be looking at the genomic data to see if it can be used to better stratify patients with ASDs in terms of treatment response.
Once iTARGET has built up its omics database, consortium members plan to start developing tools that can assist in earlier diagnosis, patient stratification, and better treatment options. "[We are] definitely looking towards a variety of pathways that could change clinical practice through a deliverable that encompasses all this information," Lewis said.
She envisions that it will "not [be] just a simple gene variant plate that you run for common single nucleotide variants or copy number variants" since she feels that sort of test is "meaningless without understanding how it integrates with the clinical piece, as well."
"It'll likely be an algorithmic tool that interrelates the influences of all these different [omics data] streams together," she said.
Additionally, after the database is completed Lewis wants to take iTARGET to the next level and attempt to understand how the omics information they collect relates to brain function, which is research she plans to undertake with Shernaz Bamji, associate professor in the department of cellular and physiological studies at UBC.
"We really tried to be all encompassing and [look towards] a longer-term project," Lewis said. "But the two-year focus of the Genome BC piece is [to build up] the omics information for now."