title: Statistical characterization of multiple-reaction monitoring mass spectrometry (MRM-MS) assays for quantitative proteomics.
abstract: Multiple reaction monitoring mass spectrometry (MRM-MS) with stable isotope dilution (SID) is increasingly becoming a widely accepted assay for the quantification of proteins and peptides. These assays have shown great promise in relatively high throughput verification of candidate biomarkers. While the use of MRM-MS assays is well established in the small molecule realm, their introduction and use in proteomics is relatively recent. As such, statistical and computational methods for the analysis of MRM-MS data from proteins and peptides are still being developed. Based on our extensive experience with analyzing a wide range of SID-MRM-MS data, we set forth a methodology for analysis that encompasses significant aspects ranging from data quality assessment, assay characterization including calibration curves, limits of detection (LOD) and quantification (LOQ), and measurement of intra- and interlaboratory precision. We draw upon publicly available seminal datasets to illustrate our methods and algorithms.
authors.affiliation: The Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. manidr@broad.mit.edu
authors.forename: D R
authors.initials: DR
authors.lastname: Mani
authors.forename: Susan E
authors.initials: SE
authors.lastname: Abbatiello
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
mesh_terms: D015415:Biomarkers / Q000737:chemistry; D003627:Data Interpretation, Statistical; D007201:Indicator Dilution Techniques; D007554:Isotopes / Q000032:analysis; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods* / Q000706:statistics & numerical data*; D010455:Peptides / Q000032:analysis; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D007554:Isotopes; D010455:Peptides; D011506:Proteins