Change-Point Modeling for Concentration and CV in Multiple Reaction Monitoring: Mass Spectrometry Assays

• Activity Number: 281
• Type: Topic Contributed
• Date/Time: Tuesday, August 3, 2010 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistical Learning and Data Mining
• Author(s): Steven James Skates*+
• Companies: Massachusetts General Hospital
• Keywords: Mass spectrometry ; calibration curve ; change-point ; limit of detection ; multiple reaction monitoring

Abstract

Multiple reaction monitoring (MRM) is a mass spectrometry (MS) technique that can measure the concentration of proteins in complex biological fluids such as serum. Labeled signature peptides from a protein are spiked into the sample at known concentration and multiplied by the ratio of the signal between the endogenous unlabeled peptide and labeled peptide to give the concentration. An important step in the measurement process is determining the calibration curve from which estimates and CVs (coefficients of variation) of concentrations in unknown samples are derived. We model the MRM calibration curve's log(mean) and log(CV) with two change-point models, allowing CVs to increase as concentration decreases, and plateau below the limit of detection. CVs of unknowns account for the variation in replicate measurements and the uncertainty of the parameters describing the calibration curve.