Current methods for the prediction of mixture toxicity have shown to be valid for mixtures that conform to some assumptions that were ideally formulated for mixtures comprising constituents exhibiting either completely similar or dissimilar mechanisms of action. Approaches are needed that predict the toxicity of mixtures representative of real environmental occurrences i.e., those comprising constituents of mixed similar and dissimilar compounds and therefore are more complex. In this paper such a methodology is proposed which uses molecular descriptors and fuzzy set theory to characterize the degree of similarity and dissimilarity of mixture constituents, integrates the concentration addition and independent action models, and therefore is called INFCIM (INtegrated Fuzzy Concentration addition--Independent action Model). INFCIM is tested in two case studies using toxicity data of four mixtures, and its performance is compared against those of both concentration addition and independent action models. Mixture 1 consists of 18 s-triazines acting on green freshwater algae scenedemus vacuolatus. Mixture 2 comprises 16 acting constituents tested on scenedemus vacuolatus. Both mixtures inhibit reproduction in the biological assays. There are 10 quinolone compounds in mixture 3 and 16 phenol derivative compounds in mixture 4 all causing long-term inhibition of bioluminescence in the marine bacterium Vibrio fischeri. It was shown that INFCIM performed comparably or better than the best performing existing model in the original studies for all the mixtures tested.
Automatic induction of decision trees and production rules from data to develop structure-activity models for toxicity prediction has recently received much attention, and the majority of methodologies reported in the literature are based upon recursive partitioning employing greedy searches to choose the best splitting attribute and value at each node. These approaches can be successful; however, the greedy search will necessarily miss regions of the search space. Recent literature has demonstrated the applicability of genetic programming to decision tree induction to overcome this problem. This paper presents a variant of this novel approach, using fewer mutation options and a simpler fitness function, demonstrating its utility in inducing decision trees for ecotoxicity data, via a case study of two data sets giving improved accuracy and generalization ability over a popular decision tree inducer.
Recent literature has demonstrated the applicability of genetic programming to induction of decision trees for modelling toxicity endpoints. Compared with other decision tree induction techniques that are based upon recursive partitioning employing greedy searches to choose the best splitting attribute and value at each node that will necessarily miss regions of the search space, the genetic programming based approach can overcome the problem. However, the method still requires the discretization of the often continuous-valued toxicity endpoints prior to the tree induction. A novel extension of this method, YAdapt, is introduced in this work which models the original continuous endpoint by adaptively finding suitable ranges to describe the endpoints during the tree induction process, removing the need for discretization prior to tree induction and allowing the ordinal nature of the endpoint to be taken into account in the models built.
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