- Assessing the statistical validity of proteomics based biomarkers.
- Analytica Chimica Acta
- Volume | Issue number
- 592 | 2
- Pages (from-to)
- Document type
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
A strategy is presented for the statistical validation of discrimination models in proteomics studies. Several existing tools are combined to form a solid statistical basis for biomarker discovery that should precede a biochemical validation of any biomarker. These tools consist of permutation tests, single and double cross-validation. The cross-validation steps can simply be combined with a new variable selection method, called rank products. The strategy is especially suited for the low-samples-to-variables-ratio (undersampling) case, as is often encountered in proteomics and metabolomics studies. As a classification method, principal component discriminant analysis is used; however, the methodology can be used with any classifier. A dataset containing serum samples from Gaucher patients and healthy controls serves as a test case. Double cross-validation shows that the sensitivity of the model is 89% and the specificity 90%. Potential putative biomarkers are identified using the novel variable selection method. Results from permutation tests support the choice of double cross-validation as the tool for determining error rates when the modelling procedure involves a tuneable parameter. This shows that even cross-validation does not guarantee unbiased results. The validation of discrimination models with a combination of permutation tests and double cross-validation helps to avoid erroneous results which may result from the undersampling.
- go to publisher's site
If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library, or send a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.