title: Multiplexed mass spectrometric immunoassay in biomarker research: a novel approach to the determination of a myocardial infarct.
abstract: Reported here is the development of a multiplexed mass spectrometric immunoassay (MSIA) for the detection of myocardial infarction (MI). The assay is the product of a study that systematically progresses from biomarker discovery--to identification and verification--to assay design, data analysis, and statistical challenge. During targeted population proteomics investigations, two novel biomarkers, serum amyloid A1alpha and S-sulfated transthyretin, were found to be responsive to MI. These putative markers were subsequently screened in larger cohorts of individuals to verify their responsiveness toward MI. Upon verification, a multiplexed assay was designed that was capable of simultaneously monitoring the new markers plus a previously established MI-marker (myoglobin). The multiplexed MSIA was applied to two 96-sample sets comprised of 48-MI/48-healthy and 19-MI/77-healthy, which served as training and case cohorts, respectively. Data evaluation using either preset reference levels or multivariate analysis exhibited sensitivities and specificities of >97%. These findings illustrate the importance of using systematic approaches in clinical proteomics to discover biomarkers and produce high-performance assays relevant to disease.
authors.affiliation: Intrinsic Bioprobes, Inc., 625 S. Smith Rd. #22, Tempe, Arizona 85281, USA.
authors.forename: Urban A
authors.initials: UA
authors.lastname: Kiernan
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
authors.forename: Randall W
authors.initials: RW
authors.lastname: Nelson
mesh_terms: D015415:Biomarkers / Q000032:analysis; D006801:Humans; D007118:Immunoassay / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D009203:Myocardial Infarction / Q000175:diagnosis*; D011228:Prealbumin / Q000032:analysis / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000235:genetics
chemical_list: D015415:Biomarkers; D011228:Prealbumin; D000685:Serum Amyloid A Protein