title: Prediction of high-responding peptides for targeted protein assays by mass spectrometry.
abstract: Protein biomarker discovery produces lengthy lists of candidates that must subsequently be verified in blood or other accessible biofluids. Use of targeted mass spectrometry (MS) to verify disease- or therapy-related changes in protein levels requires the selection of peptides that are quantifiable surrogates for proteins of interest. Peptides that produce the highest ion-current response (high-responding peptides) are likely to provide the best detection sensitivity. Identification of the most effective signature peptides, particularly in the absence of experimental data, remains a major resource constraint in developing targeted MS-based assays. Here we describe a computational method that uses protein physicochemical properties to select high-responding peptides and demonstrate its utility in identifying signature peptides in plasma, a complex proteome with a wide range of protein concentrations. Our method, which employs a Random Forest classifier, facilitates the development of targeted MS-based assays for biomarker verification or any application where protein levels need to be measured.
authors.affiliation: Broad Institute of Massachusetts Institute of Technology and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fusaro
authors.forename: D R
authors.initials: DR
authors.lastname: Mani
authors.forename: Jill P
authors.initials: JP
authors.lastname: Mesirov
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000737:chemistry*; D055598:Chemical Phenomena; D002853:Chromatography, Liquid; D019295:Computational Biology / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D015415:Biomarkers; D010455:Peptides