Authors: Martin TM; Harten P; Venkatapathy R; Das S; Young DM
Abstract: ABSTRACT A quantitative structure-activity relationship (QSAR) methodology based on hierarchical clustering was developed to predict toxicological endpoints. This methodology utilizes Ward's method to divide a training set into a series of structurally similar clusters. The structural similarity is defined in terms of 2-D physicochemical descriptors (such as connectivity and E-state indices). A genetic algorithm-based technique is used to generate statistically valid QSAR models for each cluster (using the pool of descriptors described above). The toxicity for a given query compound is estimated using the weighted average of the predictions from the closest cluster from each step in the hierarchical clustering assuming that the compound is within the domain of applicability of the cluster. The hierarchical clustering methodology was tested using a Tetrahymena pyriformis acute toxicity data set containing 644 chemicals in the training set and with two prediction sets containing 339 and 110 chemicals. The results from the hierarchical clustering methodology were compared to the results from several different QSAR methodologies.
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Journal: Toxicology mechanisms and methods Volume: 18 Issue: 2-3 Pages: 251-66 Date: Jan. 1, 2008 PMID: 20020919 |
Martin TM, Harten P, Venkatapathy R, Das S, Young DM (2008) A hierarchical clustering methodology for the estimation of toxicity. Toxicology mechanisms and methods 18: 251-66.
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