Statistical characterization of multiple-reaction monitoring mass spectrometry (MRM-MS) assays for quantitative proteomics

• Main Authors: Mani, D. R. (Author), Abbatiello, Susan E (Author), Carr, Steven A (Author)
• Other Authors: Koch Institute for Integrative Cancer Research at MIT (Contributor), Carr, Steven A. (Contributor)
• Format: Article
• Language: English
• Published: BioMed Central Ltd, 2012-11-06T17:41:19Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Cancer Institute (U.S.) (Grant U24CA126476)
National Heart, Lung, and Blood Institute (Grant HHSN268201000033C)