Categorical QSAR models for skin sensitization based upon local lymph node assay classification measures part 2: 4D-fingerprint three-state and two-2-state logistic regression models
Categorical QSAR models for skin sensitization based upon local lymph node assay classification measures part 2: 4D-fingerprint three-state and two-2-state logistic regression models
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DOI：
10.1093/toxsci/kfm185
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发表时间：
2007-10-01
影响因子：
3.8
通讯作者：
Tseng, Yufeng J.
中科院分区：
文献类型：
--
作者：
Li, Yi;Pan, Dahua;Tseng, Yufeng J.
使用小鼠局部淋巴结试验研究的数据构建了皮肤致敏的三态和四态分类定量构效关系（QSAR）模型。这些是我们先前用于构建双态（敏化剂，非敏化剂）QSAR模型的相同数据（Li等人，2007年，毒理学化学研究。20，114-128）。来自4D-分子相似性范例的4D-指纹描述符用于生成这些模型。在这项研究中使用了196个训练集和22个结构不同的化合物的测试集。采用Logistic回归和偏最小二乘Logistic回归建立模型。三态QSAR模型对训练集和测试集的分类准确率分别为73.4%和63.6%，而对任意三态数据集的分类准确率的随机平均值为33.3%。2 -2-状态[共4类] QSAR模型对训练集和测试集的分类准确率分别为83.2%和54.6%，而对任意2 -2-状态数据集的分类准确率的随机平均值为25%。在这项研究中开发的皮肤致敏模型的分析，以及在我们以前的分析中开发的两个状态的QSAR模型，表明“温和”的致敏剂可能是有限的模型精度的主要来源。
Three and four state categorical quantitative structure-activity relationship (QSAR) models for skin sensitization have been constructed using data from the murine Local Lymph Node Assay studies. These are the same data we previously used to build two-state (sensitizer, nonsensitizer) QSAR models (Li et al., 2007, Chem. Res. Toxicol. 20, 114-128). 4D-fingerprint descriptors derived from the 4D-molecular similarity paradigm are used to generate these models. A training set of 196 and a test set of 22 structurally diverse compounds were used in this study. Logistic regression, and partial least square coupled logistic regression were used to build the models. The three-state QSAR model gives a classification accuracy of 73.4% for the training set and 63.6% for the test set, while the random average value of classification accuracy for any three-state data set is 33.3%. The two-2-state [four categories in total] QSAR model gives a classification accuracy of 83.2% for the training set and 54.6% for the test set, while the random average value of classification accuracy for any two-2-state data set is 25%. An analysis of the skin-sensitization models developed in this study, as well as the two-state QSAR models developed in our previous analysis, suggests that the "moderate" sensitizers may be the main source of limited model accuracy.