Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma

Terri A. Addona, Susan E. Abbatiello, Birgit Schilling, Steven J. Skates, D. R. Mani, David M. Bunk, Clifford H. Spiegelman, Lisa J. Zimmerman, Amy Joan L. Ham, Hasmik Keshishian, Steven C. Hall, Simon Allen, Ronald K. Blackman, Christoph H. Borchers, Charles Buck, Helene L. Cardasis, Michael P. Cusack, Nathan G. Dodder, Bradford W. Gibson, Jason M. HeldTara Hiltke, Angela Jackson, Eric B. Johansen, Christopher R. Kinsinger, Jing Li, Mehdi Mesri, Thomas A. Neubert, Richard K. Niles, Trenton C. Pulsipher, David Ransohoff, Henry Rodriguez, Paul A. Rudnick, Derek Smith, David L. Tabb, Tony J. Tegeler, Asokan M. Variyath, Lorenzo J. Vega-Montoto, Åsa Wahlander, Sofia Waldemarson, Mu Wang, Jeffrey R. Whiteaker, Lei Zhao, N. Leigh Anderson, Susan J. Fisher, Daniel C. Liebler, Amanda G. Paulovich, Fred E. Regnier, Paul Tempst, Steven A. Carr

Research output: Contribution to journalArticlepeer-review

891 Scopus citations


Verification of candidate biomarkers relies upon specific, quantitative assays optimized for selective detection of target proteins, and is increasingly viewed as a critical step in the discovery pipeline that bridges unbiased biomarker discovery to preclinical validation. Although individual laboratories have demonstrated that multiple reaction monitoring (MRM) coupled with isotope dilution mass spectrometry can quantify candidate protein biomarkers in plasma, reproducibility and transferability of these assays between laboratories have not been demonstrated. We describe a multilaboratory study to assess reproducibility, recovery, linear dynamic range and limits of detection and quantification of multiplexed, MRM-based assays, conducted by NCI-CPTAC. Using common materials and standardized protocols, we demonstrate that these assays can be highly reproducible within and across laboratories and instrument platforms, and are sensitive to low g/ml protein concentrations in unfractionated plasma. We provide data and benchmarks against which individual laboratories can compare their performance and evaluate new technologies for biomarker verification in plasma.

Original languageEnglish
Pages (from-to)633-641
Number of pages9
JournalNature Biotechnology
Issue number7
StatePublished - Jul 2009


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