title: Index-ion triggered MS2 ion quantification: a novel proteomics approach for reproducible detection and quantification of targeted proteins in complex mixtures.
abstract: Biomedical research requires protein detection technology that is not only sensitive and quantitative, but that can reproducibly measure any set of proteins in a biological system in a high throughput manner. Here we report the development and application of a targeted proteomics platform termed index-ion triggered MS2 ion quantification (iMSTIQ) that allows reproducible and accurate peptide quantification in complex mixtures. The key feature of iMSTIQ is an approach called index-ion triggered analysis (ITA) that permits the reproducible acquisition of full MS2 spectra of targeted peptides independent of their ion intensities. Accurate quantification is achieved by comparing the relative intensities of multiple pairs of fragment ions derived from isobaric targeted peptides during MS2 analysis. Importantly, the method takes advantage of the favorable performance characteristics of the LTQ-Orbitrap, which include high mass accuracy, resolution, and throughput. As such it provides an attractive targeted proteomics tool to meet the demands of systems biology research and biomarker studies.
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103, USA. wyan@systemsbiology.org
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Max
authors.initials: M
authors.lastname: Robinson
authors.forename: Jimmy
authors.initials: J
authors.lastname: Eng
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ranish
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D045424:Complex Mixtures / Q000737:chemistry*; D007249:Inflammation / Q000378:metabolism; D007477:Ions; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D011506:Proteins / Q000032:analysis* / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism
chemical_list: D045424:Complex Mixtures; D007477:Ions; D008070:Lipopolysaccharides; D010455:Peptides; D011506:Proteins