title: Comparative structure-toxicity relationship study of substituted benzenes to Tetrahymena pyriformis using shuffling-adaptive neuro fuzzy inference system and artificial neural networks.
abstract: The purpose of this study was to develop the structure-toxicity relationships for a large group of 268 substituted benzene to the ciliate Tetrahymena pyriformis using mechanistically interpretable descriptors. The shuffling-adaptive neuro fuzzy inference system (Shuffling-ANFIS) has been successfully applied to select the important factors affecting the toxicity of substituted benzenes to T. pyriformis. The results of the proposed model were compared with the model of linear-free energy response surface and also the principal component analysis Bayesian-regularized neural network (PCA-BRANN) trained using the same data. The presented model shows a better statistical parameter in comparison with the previous models. The results of the model are promising and descriptive. Five descriptors of octanol-water partition coefficient (logP), bond information content (BIC0), number of R-CX-R (C-026), eigenvalue sum from Z weighted distance matrix (SEigZ) and fragment based polar surface area (PSA) selected by Shuffling-ANFIS reveal the role of hydrophobicity, electronic and steric interactions in the mechanism of toxic action. Sequential zeroing of weights (SZW) as a sensitivity analysis method revealed that the hydrophobicity and electronic interactions play a major role in toxicity of these compounds. Satisfactory results (q(2)=0.828 and RMSE=0.348) in comparison with the previous works indicate that the Shuffling-ANFIS-ANN technique is able to model a diverse chemical class with more than one mechanism of toxicity by using simple and interpretable descriptors. Shuffling-ANFIS can be used as powerful feature selection technique, because its application in prediction of toxicity potency results in good statistical and interpretable physiochemical parameters.
authors.affiliation: Department of Chemistry, Sharif University of Technology, Tehran, Iran. jalali@sharif.edu
authors.forename: Mehdi
authors.initials: M
authors.lastname: Jalali-Heravi
authors.forename: Anahita
authors.initials: A
authors.lastname: Kyani
mesh_terms: D000465:Algorithms; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity*; D003198:Computer Simulation; D017143:Fuzzy Logic; D015233:Models, Statistical; D016571:Neural Networks, Computer; D017711:Nonlinear Dynamics; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000502:physiology*
chemical_list: D001555:Benzene Derivatives