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A protocol for building and evaluating predictors of disease state based on microarray data.

Lodewyk F A Wessels1, Marcel J T Reinders, Augustinus A M Hart

  • 1Department of Mediamatics, Faculty of Electrical Engineering, Mathematics and Computer Science, Delft University of Technology Mekelweg 4, 2628 CD Delft, The Netherlands. l.f.a.wessels@ewi.tudelft.nl

Bioinformatics (Oxford, England)
|April 9, 2005
PubMed
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Developing robust cancer outcome prediction models requires objective evaluation. This study introduces a validated protocol, demonstrating simple methods like shrunken centroids outperform complex ones for accurate gene expression analysis.

Area of Science:

  • Bioinformatics
  • Computational Biology
  • Cancer Genomics

Background:

  • Microarray gene expression data are vital for identifying cancer biomarkers.
  • Numerous computational methods exist for predictor construction, but lack objective evaluation standards.
  • No universally accepted computational approach ensures reliable outcome prediction.

Purpose of the Study:

  • To introduce a principled training and validation protocol for evaluating cancer outcome prediction methodologies.
  • To objectively assess different reporter selection strategies and predictor choices using gene expression data.

Main Methods:

  • Development and application of a standardized training and validation protocol.
  • Evaluation of reporter selection strategies (e.g., forward filtering, shrunken centroids) and predictors (e.g., nearest mean classifier, partial least squares).

Related Experiment Videos

  • Testing on six diverse gene expression datasets to assess performance across varying difficulties.
  • Main Results:

    • The proposed protocol enables objective evaluation of predictor construction methodologies.
    • Simple reporter selection strategies (forward filtering, shrunken centroids) were effective, outperforming partial least squares on four of six datasets.
    • Simpler classifiers, such as the nearest mean classifier, demonstrated superior performance compared to more complex alternatives.

    Conclusions:

    • The developed protocol offers a robust framework for evaluating computational approaches in cancer outcome prediction.
    • Objective comparison of different methods is now feasible, facilitating the advancement of reliable predictive models.
    • Simple, validated methods can achieve high performance in predicting cancer outcomes from gene expression data.