Most complete human blood-plasma proteome map to date unveiled

Researchers have identified an astounding 4,000 distinctive proteins in human blood plasma, a critical step toward cataloging biological markers for early diagnosis of cancer and other diseases.

“This is 10 times the number of proteins identified” and previously reported, said Richard D. Smith, a senior scientist and Battelle Fellow at the Department of Energy’s Pacific Northwest National Laboratory. The proteomics advance was announced Saturday at the American Association for the Advancement of Science annual meeting.

“Because there is huge interest in determining their utility as biomarkers for different diseases, I want to emphasize the large numbers of proteins now identified in plasma,” said Smith, a Battelle Fellow at PNNL and director of the National Institutes of Health Proteomics Research Resource Center at PNNL’s Richland, Wash., campus.

“The large coverage is important because proteins from distressed cells in essentially any tissue that can leak into the blood stream might be found in plasma, given sufficiently sensitive methods of analysis,” Smith said. “Thus, there is significant interest in cataloging the range of proteins present in blood plasma as potential biomarkers of disease states based upon their abundance change from normal levels.”

A fast and sensitive proteomic analysis is necessary for such massive screenings of bodily fluids as needed to confidently identify biomarkers and to bring into sharp focus proteins that are signs of trouble to come.

Proteomics is akin to reading the proteins like tea leaves, minus the mystic, and generally involves measurements aimed at determining what proteins are present and at what levels. Smith’s group has developed an advanced form of mass spectrometry for this purpose: Fourier transform ion cyclotron resonance (FTICR). PNNL’s instrumentation can ransack a sample for proteins that defy detection by other means, having recently pushed the detection limits to about 10 zeptomoles, or on the order of 6,000 individual molecules, “allowing the detection of many previously undetected lower level proteins in plasma that are then candidates for biomarkers,” Smith said.

The plasma-proteome advance is the latest in a string of milestones for the PNNL proteomics program over the past six months, as PNNL gears up to compete for the DOE’s multimillion-dollar Whole Proteome Analysis facility. This past summer the FTICR instrumentation developed at PNNL was named one of the 100 top inventions of the year by R&D Magazine, and in October NIH granted PNNL more than $10 million to establish its Research Resource center for proteomics.

PNNL is a DOE Office of Science research center that advances the fundamental understanding of complex systems and provides science-based solutions in national security, energy, chemistry, the biological sciences and environmental quality. Battelle, based in Columbus, Ohio, has operated PNNL for DOE since 1965.