title: Evaluation of matrix-assisted laser desorption/ionization-time of flight mass spectrometry proteomic profiling: identification of alpha 2-HS glycoprotein B-chain as a biomarker of diet.
abstract: Biomarkers have the potential to impact a wide range of public health concerns, including early detection of diseases, drug discovery, and improved accuracy of monitoring effects of interventions. Given new technological developments, broad-based screening approaches will likely advance biomarker discovery at an accelerated pace. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) allows for the elucidation of individual protein masses from a complex mixture with high throughput. We have developed a method for identifying serum biomarkers using MALDI-TOF and statistical analysis. However, before applying this approach to screening of complex diseases, we evaluated the approach in a controlled dietary intervention study. In this study, MALDI-TOF spectra were generated using samples from a randomized controlled trial. During separate feeding periods, 38 participants ate a basal diet devoid of fruits and vegetables and a basal diet supplemented with cruciferous (broccoli) family vegetables. Serum samples were obtained at the end of each 7-day feeding period and treated to remove large, abundant proteins. MALDI-TOF spectra were analyzed using peak picking algorithms and logistic regression models. Our bioinformatics methods identified two significant peaks at m/z values of 2740 and 1847 that could classify participants based on diet (basal vs. cruciferous) with 76% accuracy. The 2740 m/z peak was identified as the B-chain of alpha 2-HS glycoprotein, a serum protein previously found to vary with diet and be involved in insulin resistance and immune function.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, 98109, USA.
authors.forename: Breeana L
authors.initials: BL
authors.lastname: Mitchell
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasui
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.forename: Philip R
authors.initials: PR
authors.lastname: Gafken
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000737:chemistry*; D019295:Computational Biology; D018592:Cross-Over Studies; D004032:Diet; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D040901:Proteomics; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D060749:alpha-2-HS-Glycoprotein
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein