Abstract
This article presents a novel approach for developing a linear prediction rule to predict the non-genotoxic carcinogenicity potential of a new compound in the drug development pipeline. We construct the approach using data from 24-hour microarray experiments on rats treated with the compound. This method was developed to address an actual problem that we were presented with by scientists in mechanistic toxicology. Short-term, preclinical assays for non-genotoxic carcinogenicity, a toxicity commonly observed in long-term rodent carcinogenicity studies, have proven difficult to develop. A quick and early preclinical assay, such as this, is of particular interest and urgency. The linear prediction rule is derived using an Ensemble Linear Discriminant classifier. This is a hybrid approach which leverages the advantages of ensemble approaches for addressing over-fitting (a problem endemic to microarray data), and that of LDA for interpretability. In a limited comparison with some other classifiers, including random forest, we show that our approach has good predictive performance in addition to being interpretable.
Acknowledgments
The authors would like to thank James Colaianne and Peter Lord for their support of this work.