Computational protein biomarker prediction: A case study for prostate cancer

Michael Wagner, Dayanand N. Naik, Alex Pothen, Srinivas Kasukurti, Raghu Ram Devineni, Bao Ling Adam, O. John Semmes, George L. Wright

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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 SELDITOF 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.

Original languageEnglish (US)
Article number26
JournalBMC Bioinformatics
Volume5
DOIs
StatePublished - Mar 11 2004
Externally publishedYes

Keywords

  • ANOVA F-statistic
  • B/W ratio
  • Biomarker discovery
  • Feature (peak) selection
  • Prostate cancer
  • SELD1-TOF mass spectrometry
  • Statistical discrimination methods
  • Support vector machine

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

Fingerprint Dive into the research topics of 'Computational protein biomarker prediction: A case study for prostate cancer'. Together they form a unique fingerprint.

Cite this