title: Computational protein biomarker prediction: a case study for prostate cancer.
abstract: BACKGROUND
  Recent technological advances in mass spectrometry pose challenges in computational mathematics and statistics to process the mass spectral data into predictive models with clinical and biological significance. We discuss several classification-based approaches to finding protein biomarker candidates using protein profiles obtained via mass spectrometry, and we assess their statistical significance. Our overall goal is to implicate peaks that have a high likelihood of being biologically linked to a given disease state, and thus to narrow the search for biomarker candidates.
  
  
  RESULTS
  Thorough cross-validation studies and randomization tests are performed on a prostate cancer dataset with over 300 patients, obtained at the Eastern Virginia Medical School using SELDI-TOF mass spectrometry. We obtain average classification accuracies of 87% on a four-group classification problem using a two-stage linear SVM-based procedure and just 13 peaks, with other methods performing comparably.
  
  
  CONCLUSIONS
  Modern feature selection and classification methods are powerful techniques for both the identification of biomarker candidates and the related problem of building predictive models from protein mass spectrometric profiles. Cross-validation and randomization are essential tools that must be performed carefully in order not to bias the results unfairly. However, only a biological validation and identification of the underlying proteins will ultimately confirm the actual value and power of any computational predictions.
authors.affiliation: Cincinnati Children's Hospital Research Foundation and Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45229, USA. mwagner@cchmc.org
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Dayanand N
authors.initials: DN
authors.lastname: Naik
authors.forename: Alex
authors.initials: A
authors.lastname: Pothen
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kasukurti
authors.forename: Raghu Ram
authors.initials: RR
authors.lastname: Devineni
authors.forename: Bao-Ling
authors.initials: BL
authors.lastname: Adam
authors.forename: O John
authors.initials: OJ
authors.lastname: Semmes
authors.forename: George L
authors.initials: GL
authors.lastname: Wright
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000145:classification*; D019295:Computational Biology / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000145:classification*; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000235:genetics; D011897:Random Allocation; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins