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Molecular diagnosis: classification, model selection, and performance evaluation

MPG-Autoren

Markowetz,  Florian
Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons50564

Spang,  Rainer
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Markowetz, F., & Spang, R. (2005). Molecular diagnosis: classification, model selection, and performance evaluation. Methods of Information in Medicine, 44(3), 438-443.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-872C-8
Zusammenfassung
OBJECTIVES: We discuss supervised classification techniques applied to medical diagnosis based on gene expression profiles. Our focus lies on strategies of adaptive model selection to avoid overfitting in high-dimensional spaces. METHODS: We introduce likelihood-based methods, classification trees, support vector machines and regularized binary regression. For regularization by dimension reduction, we describe feature selection methods: feature filtering, feature shrinkage and wrapper approaches. In small sample-size situations efficient methods of data re-use are needed to assess the predictive power of a model. We discuss two issues in using cross-validation: the difference between in-loop and out-of-loop feature selection, and estimating model parameters in nested-loop cross-validation. RESULTS: Gene selection does not reduce the dimensionality of the model. Tuning parameters enable adaptive model selection. The feature selection bias is a common pitfall in performance evaluation. Model selection and performance evaluation can be combined by nested-loop cross-validation. CONCLUSIONS: Classification of microarrays is prone to overfitting. A rigorous and unbiased assessment of the predictive power of the model is a must.