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HUPO 2017 Sees Increased Emphasis On Translational, Clinical Work


NEW YORK (GenomeWeb) – Mirroring developments in the field, the annual meeting of the Human Proteome Organization last week in Dublin showed continued movement towards more applied research as well as increased integration with other omics disciplines.

HUPO's flagship projects, most notably its efforts to catalog the full human proteome, have traditionally tilted more toward discovery science, Stanford University's Michael Snyder, the organization's current president noted in an interview with GenomeWeb. But, he said, the recent meeting saw a significant amount of translational and clinical work.

One indication of this shift, and the growing interest in proteomics as a clinical tool more generally, was former US Vice President Joseph Biden's address at the meeting's kick-off dinner, where he discussed the Cancer Moonshot program and international cancer research efforts more generally.

While some researchers have expressed concerns the program would incorporate little proteomics work, in fact, proteomics and proteogenomic research in particular, have factored significantly into the project thus far.

For instance, the Moonshot's Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) Network, is currently building a system in which VA and DoD cancer patients routinely undergo proteogenomic profiling with the goal of matching their tumor types to targeted therapies. Announced last year, the project is initially focused on analyzing a cohort of 8,000 lung cancer patients drawn from the VA and DoD systems, and plans to ultimately expand into a broad range of cancers.

"Proteomics in particular has a significant role in the Cancer Mooonshot," Snyder said, noting that this marks a change from many large government omics initiatives in the past, which have largely focused on genomics.

He attributed the field's substantial presence in the program to the success of initiatives like the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), which, he said, has demonstrated that protein-level data can add information not apparent from genomic analyses.

One factor driving proteomics toward the clinic has been the development of technologies and workflows capable of running hundreds or thousands of samples. Snyder noted, in particular, a number of studies presented at the meeting using data-independent acquisition (DIA) mass spec to achieve higher throughput than was previously feasible.

"I think with DIA you are seeing a lot more through, so people are able to do larger studies than they used to be able to, and that has been a big plus," he said. "It really showed up at this meeting where you saw people analyzing hundreds of samples, which I have to confess, didn't happen so much before."

The meeting also saw a bit of vendor news on the DIA front, as Waters and Biognosys announced a comarketing agreement covering the former's SONAR DIA mass spec method.

Snyder said a number of researchers also presented work analyzing the sort of small sample sizes often used in clinical settings, including several studies on single-cell proteomic analyses.

Bruker's release of its timsTOF Pro instrument fit with this trend, as Max Planck Institute of Biochemistry researcher Matthias Mann presented on the ability of this instrument combined with his lab's PASEF (Parallel Accumulation - Serial Fragmentation) mass spec method, to analyze extremely small sample volumes.

In his presentation, Mann showed data from several experiments using the new instrument and method. From 5 μg of HeLa cell digest split into 24 fractions with each fraction run on a 45-minute gradient they identified 9,348 proteins. In a single-shot experiment using a 30-minute LC gradient they identified roughly 4,000 proteins and 800 unique proteins per minute. And in an experiment starting with 3.125 ng of HeLa digest, the equivalent of roughly 15 cells, they identified 1,803 proteins.

Snyder cited multi-omic "wellness" studies as another area of growing activity represented at the conference. Snyder himself is a leading researcher in this area, with his lab most famously having published a study in 2012 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.

Since then he has launched several other such projects, including the Integrative Personal Omics Profile, or iPOP, project, which follows around 100 individuals, collecting molecular data on them every three months. At last year's HUPO meeting he launched his Human Personal Omics Profiling (hPOP) Project, through which he aims to similarly collect proteomic and other data on meeting attendees each year.

According to Snyder, 106 peopled enrolled in the hPOP project at the 2016 meeting and 115 enrolled at last week's meeting, with around 15 subjects providing samples at both meetings.

In addition to his lab's efforts, Snyder noted presentations by Mathias Uhlén, professor of microbiology at Sweden's Royal Institute of Technology, and Leroy Hood, president of the Institute for Systems Biology, describing the use of multi-omic profiling for wellness monitoring.

The meeting also saw the continuation of the discovery and cataloguing projects that have long been central to the HUPO effort, as the organization's Chromosome-Centric Human Proteome Project, which aims to find protein evidence for the roughly 20,000 protein-coding genes in humans, progressed toward this goal.

According to a paper published last month in the Journal of Proteome Research, there remain 2,579 "missing proteins," which is down from 2,949 in 2016.

"So there is a big push to try to fill that in," Snyder said, adding that the project is also beginning to focus on adding information on protein post-translational modifications.

"My sense is that the field is maturing and moving on really well," he said. "I remember [earlier HUPO] meetings always being, here's what we're going to do, and I feel like now some things are really happening, they are really getting done."