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Stanford's Snyder Launching New Personalized Omics Profiling Project

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NEW YORK (GenomeWeb) – Stanford University's Michael Snyder is building on his already extensive work in personal omics profiling with a new project that aims to collect molecular data including genomic, transcriptomic, proteomic, and metabolomics information on thousands of subjects over a period of years.

Snyder and his colleagues plan to launch a pilot version of the project, named the Human Personal Omics Profiling Project (hPOP) at the annual meeting of the US Human Proteome Organization in Boston next week where they hope to collect samples from at least 40 attendees. The formal launch of project is planned for September at this year's World HUPO meeting in Taipei, Taiwan, where the researchers hope to enroll another 1,000 subjects.

HUPO has endorsed the effort and placed it within the framework of the organization's Human Proteome Projects, Snyder told GenomeWeb. He added that, depending on interest, he might in the future look to enlist additional research organizations like the Human Genome Organization.

Chair of the Department of Genetics at Stanford's School of Medicine, Snyder has done significant previous research into personal omics profiling. Perhaps most famously, in 2012, his lab published a study analyzing his genome, transcriptome, proteome, metabolome, and autoantibody profiles over a period of one to two years, during which time he was able to detect in himself and subsequently manage the early development of type 2 diabetes.

That work served as proof-of-concept for a larger project called the Integrative Personal Omics Profile, or iPOP, project, that Snyder and his colleagues currently have underway. That project is following 100 individuals, collecting data on their various molecular profiles every three months. In an interview with GenomeWeb last month, Snyder noted that the project has already provided some participants with actionable information, including detecting in one a genetic mutation putting her at high risk for the cancer paraganglioma and another with a mutation putting him at high risk for cardiac events.

As described by Snyder this week, the HUPO-based profiling project is still in early stages compared to the iPOP effort, but it could potentially provide a wealth of samples and longitudinally collected omics data on subjects around the world.

The goal is to collect samples from HUPO attendees at each year's conference, and, given that the meeting moves to a different region of the world each year, this will potentially allow the researchers to look at ethnic-based omics variations, Snyder noted.

"When it is in Taipei this year, the number one constituent will be Asian," he said. Whereas, "next year in Dublin [the site of the 2017 HUPO meeting], I'm expecting it will be very heavily European. So, by engaging folks from around the world we should get a more interesting [idea] of what people look like around the world at all different molecular levels."

That said, priority will be given to repeat participants who provide the project with longitudinal omics profiles, Sara Ahadi, a postdoctoral fellow in Snyder's lab who is working on the effort, told GenomeWeb.

Snyder said he envisioned the project being a forum for a variety of researchers to try out their favorite assays. Indeed, he noted, signs of such interest were already evident last year when he first proposed the initiative.

"When I brought it up at the HUPO meeting last year, very quickly someone said, 'Well, why aren't you doing glycosylation,'" he recalled. "And my reaction was, 'Great, let's move it forward.'"

"We are going to make this a community project, and I think that is the power of it, which is to say that lots of people who are world experts can bring their assays to bear on these particular samples," Snyder said.

"Where we may hit issues is whether we can get enough material to run as many assays as are desirable, but that is why we are piloting this now," he said. "We could certainly draw more blood, but then that means more processing, so there is a tradeoff."

Some sort of committee will likely be required to determine who is given access to samples collected through the project, but, Snyder said, the precise details have yet to be worked out. In general, he said, his aim is to get things off the ground and then iron out the finer details.

"A lot of things start out as theoretical, and they never go anywhere, but if we start a pilot to do this, I think people will take it seriously and then we will see who wants to sign up," he said. He and his colleagues are taking a similar approach to funding.

"I've always felt that you never get money proposing things, you always get money once you do something," he said. "So once we get started, I hope others will show their generosity to make this happen. We will see."

The researchers will collect blood, urine, and stool from participants and currently have funding for proteomic analyses on the plasma and PBMCs and metabolomics analyses on the urine and plasma, Hannes Röst, a bioinformatician in Snyder's lab, told GenomeWeb. Ultimately, they hope to add a variety of other measurements, including RNA and genome sequencing of the PBMCs and microbiome analysis of stool samples. All data from the project will be made publicly available, Röst added.

Initially, the proteomic portion of the project will be done using Swath mass spec on an instrument donated for the effort by Sciex and through antibody-based assays by the lab of Royal Institute of Technology Sweden researcher Mathias Uhlén.

The project is not formally related to the ongoing iPOP effort, but Snyder said that project has given his group valuable experience in undertaking such large-scale omics work.

One question regarding such intensive longitudinal sampling of omics data is how to distinguish between significant variations in a person's omics profile that warrant clinical attention from changes that their body will ultimately resolve on its own. This, Snyder noted, becomes particularly important as the researchers move from the relatively static genomic data to more dynamic types of data like proteomic and metabolomic information.

He cited the example of his own situation. "When my glucose shot through the roof, some people said, 'Mike, you don't know that wouldn't have gone away on its own,'" he said. "But I didn't really want to be in that position of waiting around for many months to see if that was the case. And it is pretty clear knowing what I know now that it wouldn't have gone away on its own, because I did get it down by exercising but it did come back later when I stopped exercising."

Snyder said that under the conditions set by the project's institutional review board, the researchers are not allowed to return results directly to participants, but they would deliver them to their physicians if their measurements turned up some concerning data.

"If we found changes that could impact their health, we think it would be nice to get it back to them, and then if it really is there and reproducible [in a CLIA setting], I would minimally keep an eye on it, and, maximally, you might want to do something about it," Snyder said.

Ultimately, he noted, projects like hPOP and iPOP are necessary for researchers and clinicians to begin to better determine what fluctuations are and are not significant.

"Quite frankly, you are only going to get that kind of information if you profile enough people over a long enough period of time," he said.

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