title: Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma.
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 mug/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.
authors: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
authors: Terri A
authors: TA
authors: Addona
authors: Susan E
authors: SE
authors: Abbatiello
authors: Birgit
authors: B
authors: Schilling
authors: Steven J
authors: SJ
authors: Skates
authors: D R
authors: DR
authors: Mani
authors: David M
authors: DM
authors: Bunk
authors: Clifford H
authors: CH
authors: Spiegelman
authors: Lisa J
authors: LJ
authors: Zimmerman
authors: Amy-Joan L
authors: AJ
authors: Ham
authors: Hasmik
authors: H
authors: Keshishian
authors: Steven C
authors: SC
authors: Hall
authors: Simon
authors: S
authors: Allen
authors: Ronald K
authors: RK
authors: Blackman
authors: Christoph H
authors: CH
authors: Borchers
authors: Charles
authors: C
authors: Buck
authors: Helene L
authors: HL
authors: Cardasis
authors: Michael P
authors: MP
authors: Cusack
authors: Nathan G
authors: NG
authors: Dodder
authors: Bradford W
authors: BW
authors: Gibson
authors: Jason M
authors: JM
authors: Held
authors: Tara
authors: T
authors: Hiltke
authors: Angela
authors: A
authors: Jackson
authors: Eric B
authors: EB
authors: Johansen
authors: Christopher R
authors: CR
authors: Kinsinger
authors: Jing
authors: J
authors: Li
authors: Mehdi
authors: M
authors: Mesri
authors: Thomas A
authors: TA
authors: Neubert
authors: Richard K
authors: RK
authors: Niles
authors: Trenton C
authors: TC
authors: Pulsipher
authors: David
authors: D
authors: Ransohoff
authors: Henry
authors: H
authors: Rodriguez
authors: Paul A
authors: PA
authors: Rudnick
authors: Derek
authors: D
authors: Smith
authors: David L
authors: DL
authors: Tabb
authors: Tony J
authors: TJ
authors: Tegeler
authors: Asokan M
authors: AM
authors: Variyath
authors: Lorenzo J
authors: LJ
authors: Vega-Montoto
authors: Asa
authors: A
authors: Wahlander
authors: Sofia
authors: S
authors: Waldemarson
authors: Mu
authors: M
authors: Wang
authors: Jeffrey R
authors: JR
authors: Whiteaker
authors: Lei
authors: L
authors: Zhao
authors: N Leigh
authors: NL
authors: Anderson
authors: Susan J
authors: SJ
authors: Fisher
authors: Daniel C
authors: DC
authors: Liebler
authors: Amanda G
authors: AG
authors: Paulovich
authors: Fred E
authors: FE
authors: Regnier
authors: Paul
authors: P
authors: Tempst
authors: Steven A
authors: SA
authors: Carr
mesh_terms: D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods; D001798:Blood Proteins / Q000032:analysis*; D006801:Humans; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D020543:Proteome / Q000032:analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013673:Technology Assessment, Biomedical
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome