By Edward Farmer, Vice President, WuXi NextCODE
“It’s only by connecting this diverse body of researchers with each other, and with a wide range of datasets in each area, that we have any hope of having a real-world impact on the lives of individuals and families who are struggling with autism.”
Due to the brain’s complexity, neurodevelopmental disorders are one of the most difficult challenges scientists face. Genomics offers one of the most promising avenues to unravel that complexity but the heterogeneity of the autism spectrum demands vast amounts of data to find meaningful signals. That is why the combination of exome and whole-genome sequencing, and global collaboration are so promising.
Assembling and making such datasets available are among the principal goals of Alan Packer and his colleagues at the Simons Foundation, the world’s leading private funding body for autism research. The Foundation’s Autism Research Initiative (SFARI) recently teamed up with WuXi NextCODE to put the Simons Simplex Collection (SSC) – the world’s largest autism dataset – online. The WuXi NextCODE Simons Simplex portal includes 10,000 exomes with integrated clinical discovery tools, making it possible for autism researchers around the world to query the entire collection, at raw resolution, instantly and directly in real time over an ordinary internet connection.
We spoke recently with Dr Packer, Senior Scientist at SFARI, about how this online portal can help to inaugurate a new era of genome research on a vast and truly global scale.
Edward Farmer: What is the main purpose of the SSC data? What have been its main achievements to date?
Alan Packer: From the point of view of genetics, the main goal of the SSC is to identify mutations—particularly de novo mutations—that confer strong risk of autism outside the context of a handful of medical syndromes that are frequently characterized by autistic features. Combined with other DNA sequencing efforts in autism, the SSC has helped identify at least 70 such genetic risk factors, providing neurobiologists for the first time with significant clues about processes in the developing brain that may underlie the disorder. I think the family-based design of the SSC has also been influential in other fields where the search for genetic risk factors is ongoing. Finally, the SSC also has a great deal of phenotypic information about the individuals who were recruited, which has also been a boon to research in the field.
Edward Farmer: Do you think this new online portal will make the SSC data easier for researchers to use?
Alan Parker: I’m certain that this new online portal will make it easier for researchers to use the SSC data. I imagine this will be particularly true for researchers who do not have the computational capacity or bioinformatics background to manage and analyze the data without this kind of supporting platform.
Edward Farmer: Do you think that it may help expand the number and geographic spread of people accessing the data?
Alan Parker: We are indeed hopeful that our partnership with WuXi NextCODE will expand access to SSC data to investigators outside of North America. The network of contacts that WuXi has in other parts of the world, including China, is already making the collection known and available to a broader range of researchers.
Edward Farmer: Has the Simons Foundation ever had many affiliated autism researchers in China, and would it be interested in expanding the research network there?
Alan Parker: Unfortunately, the Simons Foundation has not yet supported many autism researchers in China. I assume this is mostly due to a lack of awareness of the Foundation and its efforts. We know that there is a tremendous amount of scientific talent in China, as well as interest in autism, and we would certainly encourage such researchers to read about our programs on our website (sfari.org).
Edward Farmer: Do you think that more extensive autism research in China may find genetic variants that are different from those in other populations?
Alan Parker: I think it’s an open question as to whether there are genetic variants predisposing to autism that are specific to individuals of Asian ancestry. Given the recruitment of appropriate autism cohorts in China, it’s certainly worth exploring.
Edward Farmer: Is it important to autism research to connect more researchers and datasets? Why?
Alan Parker: Neurodevelopmental disorders constitute one of the most difficult scientific challenges we face, given their heterogeneity, and the complexity of the brain. If there’s one thing I’ve learned in my seven years at the Simons Foundation, it’s the importance of encouraging investigators with a broad range of scientific expertise to work on the problem—including geneticists, cell biologists, neuroscientists, psychologists, clinicians, medicinal chemists and others. It’s only by connecting this diverse body of researchers with each other, and with a wide range of datasets in each area, that we have any hope of having a real-world impact on the lives of individuals and families who are struggling with autism. We strongly encourage Chinese investigators interested in working on autism to explore the SSC dataset and to reach out to the Simons Foundation Autism Research Initiative (sfari.org) with questions, ideas, and formal applications.