The National Institutes of Health Disruptive Proteomics Technologies Working Group is soliciting recommendations on technologies and methodologies that could lead to dramatic improvements in proteomics research capabilities.
According to a request for information issued last week, the project aims to identify technologies that could deliver "very rapid, very significant gains, similar to the 'disruptive' technology development that occurred in DNA sequencing technology." The solicitation aims to "collect information from the broader research community to assess the needs/gaps and opportunities in both [mass spec] and non-[mass spec] approaches for discovery-based proteomics."
The initiative was submitted last summer by the National Human Genome Research Institute with the support of other NIH Institutes as a potential NIH Common Fund program, and has been selected as an idea for further exploration, NHGRI program director Tina Gatlin told ProteoMonitor.
The initiative is now "in the strategic planning phase, which involves soliciting community input, which [is being done] through this RFI," Gatlin said. Upon completion of the RFI, the DPT working group will submit to the institute's Common Fund input from the solicitation along with an internal review of NIH's existing proteomics investments. The Common Fund will then decide whether to move ahead with the program.
A decision on funding the DPT proposal would likely come this summer, Gatlin said, with any program that emerged from the process likely starting in fiscal year 2013 with the solicitation of new requests for applications.
In the recent solicitation, the DPT group requested information on several topics including: "Realistic goals and associated challenges for orders-of-magnitude improvements in the dynamic range, sensitivity, throughput, or cost" of current mass spec-based proteomics; technologies that could potentially approach or exceed mass spec with regard to dynamic range, sensitivity, throughput, or cost; the potential benefits and challenges of proteomics informatics approaches; and the potential "impacts of proteomics technology breakthroughs in basic, discovery, and translational biomedical research."
The RFI notes that while mass spec "holds good potential for further incremental improvement … opportunities for orders-of magnitude improvement are unclear." Gatlin, said, however, that this was not meant as a statement of skepticism about the future of mass spec as a technology for proteomics.
"I would say it's more [about whether] we can move beyond the incremental improvements, which have been quite significant in mass spec technology," she said.
Asked what non-mass spec technologies might show promise for proteomics, Gatlin cited nanopore sequencing, parallel Edman sequencing, and protein arrays as approaches potentially worth further exploration.
Although the size and scope of the program – and whether it will even be approved for funding – remain to be determined, the project's stated discovery focus will likely reinforce existing concerns within the proteomics community about the level of support for discovery efforts compared to translational and clinical work (PM 2/17/2012).
Indeed, Arizona State University researcher Randal Nelson told ProteoMonitor he thought mass spec-based proteomics has matured to the point at which new "disruptive" technologies are less important than developing "the ability to analyze thousands of samples [in order] to get some statistics behind [proteomic] findings and why they're valuable."
"It'll take ten years before a new disruptive technology is mature enough to actually answer that problem," said Nelson, whose work largely uses mass spec to study protein biomarkers and protein microheterogeneity. In September, Intrinsic Bioprobes, a mass spec-based proteomics firm he founded, was purchased by Thermo Fisher Scientific.
"In my mind the disruptive [technology] is the integration of validated, high-throughput technologies into proteomics to actually repeatedly do experiments," he said. "Then you're one step closer to the clinic."
Although Gatlin declined to comment on the issue of the merits of funding additional discovery work versus moving toward a more translational focus, she said that she was "quite familiar with that conversation" and that the DPT group in its "internal conversations" was "aware" of the debate.
George Mason University researcher Emanuel Petricoin suggested that one issue the RFI might run into is reluctance by scientists to share their best ideas on behalf of a program that is basically still in the planning stages.
"Why am I going to tell you my best idea [for disruptive proteomics technology] and then have to apply to get money after my idea has already been put out there?" he told ProteoMonitor. "You're not going to get the best ideas. You're going to get some low-level ideas that are already in the public domain that people are already working on, and so you end up going to kind of the lowest common denominator."
His misgivings about the initiative aside, Petricoin said it might take direction from recent trends in the mass spec industry, where firms have been focusing on adding sample prep steps and automation to create fully integrated mass spec workflows.
"I think people would love to see in-line coupling of upfront sample manipulation and fluidics into mass specs and proteins arrays, where you start to see more of a systems approach," he said.
"[Mass spec] companies are trying to create disruptive technologies," he noted, citing Thermo Fisher's purchase of Nelson's IBI and Agilent's ongoing work on automating SISCAPA workflows (PM 10/14/2011). "Classic mass spec companies … like Thermo and Shimadzu and Bruker … realize that they need something else to bolt onto the front of their mass specs … and they're flowing into the area where there is the most critical need, coupling those instruments to automated sample handling and processing."
"From a translational standpoint, we really need to have our discovery approaches to have the same reproducibility and sensitivity as our measurements at the bedside," Petricoin added. "You need to have mass specs be as sensitive as immunoassays if [this is] really going to … have an impact."
He also highlighted tissue-based analysis as an area ripe for development, noting that it posed its own unique challenges – in particular the small amounts of clinical material typically available to researchers.
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