title: Physicochemical and graph theoretical descriptors in developmental toxicity SAR: a comparative study.
abstract: Chemical insults to the developing fetus can lead to growth retardation, malformation, death, and functional deficits. The present study seeks to determine if physicochemical and/or graph theoretical parameters can be used to determine a structure-activity relationship (SAR) for developmental toxicity, and if consistency is observed among the selected features. The biological data utilized consists of a diverse series of compounds evaluated within the Chernoff-Kavlock in vivo mouse assay. Physicochemical parameters calculated correspond to electronic, steric, and transport properties. Graph theoretical parameters calculated include the simple, valence, and kappa indices. Both sets of parameters were independently applied to derive SARs in order to compare the quality of the respective models. Multiple random sampling, without replacement, was utilized to obtain ten training/test partitions. Models were built by linear discriminant analysis, decision trees, and neural networks respectively. Comparisons on identical sets of data were carried out to determine if any of the model building procedures had a significant advantage in terms of predictive performance. Furthermore, comparison of the features selected within and across the model building processes led to the determination of model consistency. Our results indicate that consistent features related to developmental toxicity are observed and that both physicochemical and graph theoretical parameters have equal utility.
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238 USA. macina+@pitt.edu
authors.forename: O T
authors.initials: OT
authors.lastname: Macina
authors.forename: N B
authors.initials: NB
authors.lastname: Sussman
authors.forename: H G
authors.initials: HG
authors.lastname: Claycamp
authors.forename: S G
authors.initials: SG
authors.lastname: Grant
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016208:Databases, Factual; D005260:Female; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D011247:Pregnancy; D013329:Structure-Activity Relationship; D013723:Teratogens / Q000494:pharmacology / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D013723:Teratogens