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Nat Biotechnol DOI:10.1038/nbt.1524

Prediction of high-responding peptides for targeted protein assays by mass spectrometry.

Publication TypeJournal Article
Year of Publication2009
AuthorsFusaro, VA, Mani, DR, Mesirov, JP, Carr, SA
JournalNat Biotechnol
Date Published2009 Feb
KeywordsAlgorithms, Biomarkers, Chemical Phenomena, Chromatography, Liquid, Computational Biology, HeLa Cells, Humans, Peptides, Reproducibility of Results, Sensitivity and Specificity, Spectrometry, Mass, Electrospray Ionization

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.


Alternate JournalNat. Biotechnol.
PubMed ID19169245
PubMed Central IDPMC2753399
Grant ListR01 GM074024 / GM / NIGMS NIH HHS / United States
R01 CA126219 / CA / NCI NIH HHS / United States
1U24 CA126476 / CA / NCI NIH HHS / United States
U01 HL081341-03 / HL / NHLBI NIH HHS / United States
U01-HL081341 / HL / NHLBI NIH HHS / United States
U24 CA126476-03 / CA / NCI NIH HHS / United States
U01 HL081341 / HL / NHLBI NIH HHS / United States
R01 CA126219-02 / CA / NCI NIH HHS / United States
U24 CA126476 / CA / NCI NIH HHS / United States
R01 GM074024-03 / GM / NIGMS NIH HHS / United States