Document Detail


Physicochemical and graph theoretical descriptors in developmental toxicity SAR: a comparative study.
MedLine Citation:
PMID:  11328709     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
O T Macina; N B Sussman; H G Claycamp; S G Grant
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  SAR and QSAR in environmental research     Volume:  11     ISSN:  1062-936X     ISO Abbreviation:  SAR QSAR Environ Res     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-04-30     Completed Date:  2001-06-14     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9440156     Medline TA:  SAR QSAR Environ Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  345-62     Citation Subset:  IM    
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
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemistry, Physical
Databases, Factual
Female
Humans
Mice
Models, Theoretical*
Physicochemical Phenomena
Pregnancy
Structure-Activity Relationship
Teratogens / pharmacology,  toxicity*
Toxicity Tests / methods,  statistics & numerical data
Grant Support
ID/Acronym/Agency:
1-55(ESO9460-01 AI/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Teratogens

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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