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 journalArticle

761 Citations (Scopus)

Abstract

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
Volume27
Issue number7
DOIs
StatePublished - Jul 2009

Fingerprint

Biomarkers
Blood Proteins
Assays
Proteins
Plasmas
Monitoring
Benchmarking
Isotopes
Dilution
Mass spectrometry
Limit of Detection
Mass Spectrometry
Pipelines
Technology
Network protocols
Recovery

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Addona, T. A., Abbatiello, S. E., Schilling, B., Skates, S. J., Mani, D. R., Bunk, D. M., ... Carr, S. A. (2009). Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nature Biotechnology, 27(7), 633-641. https://doi.org/10.1038/nbt.1546

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

In: Nature Biotechnology, Vol. 27, No. 7, 07.2009, p. 633-641.

Research output: Contribution to journalArticle

Addona, TA, Abbatiello, SE, Schilling, B, Skates, SJ, Mani, DR, Bunk, DM, Spiegelman, CH, Zimmerman, LJ, Ham, AJL, Keshishian, H, Hall, SC, Allen, S, Blackman, RK, Borchers, CH, Buck, C, Cardasis, HL, Cusack, MP, Dodder, NG, Gibson, BW, Held, JM, Hiltke, T, Jackson, A, Johansen, EB, Kinsinger, CR, Li, J, Mesri, M, Neubert, TA, Niles, RK, Pulsipher, TC, Ransohoff, D, Rodriguez, H, Rudnick, PA, Smith, D, Tabb, DL, Tegeler, TJ, Variyath, AM, Vega-Montoto, LJ, Wahlander, Å, Waldemarson, S, Wang, M, Whiteaker, JR, Zhao, L, Anderson, NL, Fisher, SJ, Liebler, DC, Paulovich, AG, Regnier, FE, Tempst, P & Carr, SA 2009, 'Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma', Nature Biotechnology, vol. 27, no. 7, pp. 633-641. https://doi.org/10.1038/nbt.1546
Addona, Terri A. ; Abbatiello, Susan E. ; Schilling, Birgit ; Skates, Steven J. ; Mani, D. R. ; Bunk, David M. ; Spiegelman, Clifford H. ; Zimmerman, Lisa J. ; Ham, Amy Joan L ; Keshishian, Hasmik ; Hall, Steven C. ; Allen, Simon ; Blackman, Ronald K. ; Borchers, Christoph H. ; Buck, Charles ; Cardasis, Helene L. ; Cusack, Michael P. ; Dodder, Nathan G. ; Gibson, Bradford W. ; Held, Jason M. ; Hiltke, Tara ; Jackson, Angela ; Johansen, Eric B. ; Kinsinger, Christopher R. ; Li, Jing ; Mesri, Mehdi ; Neubert, Thomas A. ; Niles, Richard K. ; Pulsipher, Trenton C. ; Ransohoff, David ; Rodriguez, Henry ; Rudnick, Paul A. ; Smith, Derek ; Tabb, David L. ; Tegeler, Tony J. ; Variyath, Asokan M. ; Vega-Montoto, Lorenzo J. ; Wahlander, Åsa ; Waldemarson, Sofia ; Wang, Mu ; Whiteaker, Jeffrey R. ; Zhao, Lei ; Anderson, N. Leigh ; Fisher, Susan J. ; Liebler, Daniel C. ; Paulovich, Amanda G. ; Regnier, Fred E. ; Tempst, Paul ; Carr, Steven A. / Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. In: Nature Biotechnology. 2009 ; Vol. 27, No. 7. pp. 633-641.
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AU - Tegeler, Tony J.

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AU - Vega-Montoto, Lorenzo J.

AU - Wahlander, Åsa

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