Prediction of the skin sensitising potential and potency of compounds via mechanism-based binary and ternary classification models.

Skin sensitisation, one of the most frequent forms of human immune toxicity, is authenticated to be a significant endpoint in the field of drug discovery and cosmetics. Due to the drawbacks of traditional animal testing methods, in silico methods have advanced to study skin sensitisation. In this study, mechanism-based binary and ternary classification models were constructed with a comprehensive data set. 1007 compounds were collected to develop five series of local and global models based on mechanisms. In each series, compounds were classified into five groups according to EC3 values, and applied as training sets, test sets and external validation sets. For each of the five series, 81 binary classification models and 81 ternary classification models were acquired via 9 molecular fingerprints and 9 machine learning methods using a novel KNIME workflow. Meanwhile, the applicability domains for the best 10 models were figured out to certify the rationality of prediction effect. In addition, 8 toxic substructures probably causing skin sensitisation were identified to speculate whether a compound is a skin sensitiser. The mechanism-based prediction models and the toxic substructures can be applied to predict the skin sensitising potential and potency of compounds.

Quantitative Regression Models for the Prediction of Chemical Properties by an Efficient Workflow.

Rapid safety assessment is more and more needed for the increasing chemicals both in chemical industries and regulators around the world. The traditional experimental methods couldn't meet the current demand any more. With the development of the information technology and the growth of experimental data, in silico modeling has become a practical and rapid alternative for the assessment of chemical properties, especially for the toxicity prediction of organic chemicals. In this study, a quantitative regression workflow was built by KNIME to predict chemical properties. With this regression workflow, quantitative values of chemical properties can be obtained, which is different from the binary-classification model or multi-classification models that can only give qualitative results. To illustrate the usage of the workflow, two predictive models were constructed based on datasets of Tetrahymena pyriformis toxicity and Aqueous solubility. The qcv (2) and qtest (2) of 5-fold cross validation and external validation for both types of models were greater than 0.7, which implies that our models are robust and reliable, and the workflow is very convenient and efficient in prediction of various chemical properties.