Mutagenic probability estimation of chemical compounds by a novel molecular electrophilicity vector and support vector machine
Mutagenic probability estimation of chemical compounds by a novel molecular electrophilicity vector and support vector machine
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DOI：
10.1093/bioinformatics/btl352
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发表时间：
2006-08
期刊：
影响因子：
5.8
通讯作者：
M. Zheng;Zhiguo Liu;Chunxiao Xue;Weiliang Zhu;Kaixian Chen;Xiaomin Luo;Hualiang Jiang
中科院分区：
文献类型：
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作者：
M. Zheng;Zhiguo Liu;Chunxiao Xue;Weiliang Zhu;Kaixian Chen;Xiaomin Luo;Hualiang Jiang
致突变性是引起最高关注的毒理学终点之一。药物发现的加速步伐提高了对有效预测方法的需求。目前，大多数可用的工具达不到所需的准确度，只能提供二进制分类。建立一个判别性强、信息量大的致突变性预测模型具有重要意义。结果在这里，我们开发了一个诱变概率预测模型来解决这个问题，基于覆盖大化学空间的数据集。首次设计了一种新的分子亲电性矢量（MEV）来表征化合物的结构轮廓。然后使用扩展支持向量机（SVM）方法从训练集的MEV中推导出致突变性的后验概率估计。结果表明，该模型比TOPKAT（http：//www.example.com）和其他已发表的方法具有更好的性能. www.accelrys.com此外，可以提供与预测相关的置信水平，这可以帮助人们对化学排序或合成做出更灵活的决策。可用性基于我们的模型的二进制程序（ZGTOX_1.1）和Windows PC上的输入数据集的样本可在http://dddc.ac.cn/adme上根据作者的要求获得。
MOTIVATION Mutagenicity is among the toxicological end points that pose the highest concern. The accelerated pace of drug discovery has heightened the need for efficient prediction methods. Currently, most available tools fall short of the desired degree of accuracy, and can only provide a binary classification. It is of significance to develop a discriminative and informative model for the mutagenicity prediction. RESULTS Here we developed a mutagenic probability prediction model addressing the problem, based on datasets covering a large chemical space. A novel molecular electrophilicity vector (MEV) is first devised to represent the structure profile of chemical compounds. An extended support vector machine (SVM) method is then used to derive the posterior probabilistic estimation of mutagenicity from the MEVs of the training set. The results show that our model gives a better performance than TOPKAT (http://www.accelrys.com) and other previously published methods. In addition, a confidence level related to the prediction can be provided, which may help people make more flexible decisions on chemical ordering or synthesis. AVAILABILITY The binary program (ZGTOX_1.1) based on our model and samples of input datasets on Windows PC are available at http://dddc.ac.cn/adme upon request from the authors.