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Open Access Highly Accessed Research article

Computational protein biomarker prediction: a case study for prostate cancer

Michael Wagner1*, Dayanand N Naik2, Alex Pothen3, Srinivas Kasukurti3, Raghu Ram Devineni3, Bao-Ling Adam4, O John Semmes4 and George L Wright4

Author Affiliations

1 Cincinnati Children's Hospital Research Foundation and Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH 45229, USA

2 Department of Mathematics and Statistics, Old Dominion University, Norfolk, VA 23529, USA

3 Department of Computer Science, Old Dominion University, Norfolk, VA 23529, USA

4 Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA

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BMC Bioinformatics 2004, 5:26  doi:10.1186/1471-2105-5-26

Published: 11 March 2004

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.

Keywords:
ANOVA F-statistic; B/W ratio; biomarker discovery; feature (peak) selection; prostate cancer; SELD1-TOF mass spectrometry; statistical discrimination methods; support vector machine.