Discriminant function analyses of liver-specific carcinogens

The ability to predict organ-specific carcinogenicity would aid FDA reviewers in evaluating new chemical applications. A NCTR liver cancer database (NCTRlcdb) containing 999 compounds has been developed with three sets of descriptors. The NCTRlcdb has Cerius2, Molconn-Z, and (13)C NMR descriptors for each compound. Each compound in the database was assigned a liver cancer or a nonliver cancer classification. Compounds within the NCTRlcdb were evaluated for liver-specific carcinogenicity using partial least squares principal component discriminant function (PLS-DF) modeling. PLS-DF models based on estimated a priori classification probabilities of 0.29 for liver cancer and 0.71 for noncancer yielded an overall predictability of 70.6% which was comprised of a liver cancer sensitivity of 18.8% and a noncancer specificity of 90.8%. PLS-DF models based on equal a priori classification probabilities, 0.50 for liver cancer and 0.5 for noncancer, yielded an overall predictability of 61.0% which was comprised of a liver cancer sensitivity of 50.5% and a noncancer specificity of 65.3%.