Prediction of genotoxicity of chemical compounds by statistical learning methods

Chem Res Toxicol. 2005 Jun;18(6):1071-80. doi: 10.1021/tx049652h.


Various toxicological profiles, such as genotoxic potential, need to be studied in drug discovery processes and submitted to the drug regulatory authorities for drug safety evaluation. As part of the effort for developing low cost and efficient adverse drug reaction testing tools, several statistical learning methods have been used for developing genotoxicity prediction systems with an accuracy of up to 73.8% for genotoxic (GT+) and 92.8% for nongenotoxic (GT-) agents. These systems have been developed and tested by using less than 400 known GT+ and GT- agents, which is significantly less in number and diversity than the 860 GT+ and GT- agents known at present. There is a need to examine if a similar level of accuracy can be achieved for the more diverse set of molecules and to evaluate other statistical learning methods not yet applied to genotoxicity prediction. This work is intended for testing several statistical learning methods by using 860 GT+ and GT- agents, which include support vector machines (SVM), probabilistic neural network (PNN), k-nearest neighbor (k-NN), and C4.5 decision tree (DT). A feature selection method, recursive feature elimination, is used for selecting molecular descriptors relevant to genotoxicity study. The overall accuracies of SVM, k-NN, and PNN are comparable to and those of DT lower than the results from earlier studies, with SVM giving the highest accuracies of 77.8% for GT+ and 92.7% for GT- agents. Our study suggests that statistical learning methods, particularly SVM, k-NN, and PNN, are useful for facilitating the prediction of genotoxic potential of a diverse set of molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Decision Support Techniques*
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions*
  • Mutagens / classification*
  • Mutagens / toxicity*
  • Pharmaceutical Preparations / classification*
  • Quantitative Structure-Activity Relationship*
  • Reproducibility of Results


  • Mutagens
  • Pharmaceutical Preparations