https://scholars.lib.ntu.edu.tw/handle/123456789/329554
標題: | 4D-fingerprint categorical QSAR models for skin sensitization based on the classification of local lymph node assay measures | 作者: | Li, Y. Pan, D. Liu, J. Kern, P.S. Gerberick, G.F. Hopfinger, A.J. YUFENG JANE TSENG |
公開日期: | 2007 | 卷: | 20 | 期: | 1 | 起(迄)頁: | 114-128 | 來源出版物: | Chemical Research in Toxicology | 摘要: | Currently, the only validated methods to identify skin sensitization effects are in vivo models, such as the local lymph node assay (LLNA) and guinea pig studies. There is a tremendous need, in particular due to novel legislation, to develop animal alternatives, for eaxample, quantitative structure-activity relationship (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been constructed. The descriptors used to generate these models are derived from the 4D-molecular similarity paradigm and are referred to as universal 4D-fingerprints. A training set of 132 structurally diverse compounds and a test set of 15 structurally diverse compounds were used in this study. The statistical methodologies used to build the models are logistic regression (LR) and partial least-square coupled logistic regression (PLS-LR), which prove to be effective tools for studying skin sensitization measures expressed in the two categorical terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer-Lemeshow goodness-of-fit statistic, χHL2, are significant and predictive. For the training set, the cross-validated prediction accuracy of the logistic regression models ranges from 77.3% to 78.0%, whereas that of the PLS-logistic regression models ranges from 87.1% to 89.4%. For the test set, the prediction accuracy of logistic regression models ranges from 80.0% to 86.7%, whereas that of the PLS-logistic regression models ranges from 73.3% to 80.0%. The QSAR models are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond acceptors, and negatively partially charged atoms. © 2007 American Chemical Society. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-33846875208&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/329554 |
ISSN: | 0893228X | DOI: | 10.1021/tx6002535 | SDG/關鍵字: | article; hydrogen bond; local lymph node assay; molecular model; pharmacophore; quantitative structure activity relation; skin allergy; skin sensitization; Animals; Guinea Pigs; Least-Squares Analysis; Logistic Models; Lymph Nodes; Quantitative Structure-Activity Relationship; Skin; Toxicity Tests; Animalia; Cavia |
顯示於: | 生醫電子與資訊學研究所 |
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