Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

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This paper considers binary classification. We assess a classifier in terms of the Area Under the ROC Curve (AUC). We estimate three important parameters, the conditional AUC (conditional on a particular training set) and the mean and variance of this AUC. We derive, as well, a closed form expression of the variance of the estimator of the AUC. This expression exhibits several components of variance that facilitate an understanding for the sources of uncertainty of that estimate. In addition, we estimate this variance, i.e., the variance of the conditional AUC estimator. Our approach is nonparametric and based on general methods from U-statistics; it addresses the case where the data distribution is neither known nor modeled and where there are only two available data sets, the training and testing sets. Finally, we illustrate some simulation results for these estimators.

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