title: A Combinational Strategy of Model Disturbance and Outlier Comparison to Define Applicability Domain in Quantitative Structural Activity Relationship.
abstract: In order to define an applicability domain for quantitative structure-activity relationship modeling, a combinational strategy of model disturbance and outlier comparison is developed. An indicator named model disturbance index was defined to estimate the prediction error. Moreover, the information of the outliers in the training set was used to filter the unreliable samples in the test set based on "structural similarity". Chromatography retention indices data were used to investigate this approach. The relationship between model disturbance index and prediction error can be found. Also, the comparison between the outlier set and the test set could provide additional information about which unknown samples should be paid more attentions. A novel technique based on model population analysis was used to evaluate the validity of applicability domain. Finally, three commonly used methods, i.e. Leverage, descriptor range-based and model perturbation method, were compared with the proposed approach.
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicine, Central South University, Changsha 410083, P. R. China tel: +86 731 8830831; fax: +86 731 8830831.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Chemical and Bioscience, HeChi University, YiZhou 546300, P. R. China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zhu
authors.affiliation: Technology Center of China Tobacco Hunan Industrial Co., LTD, Changsha 410014, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.affiliation: Technology Center of China Tobacco Hunan Industrial Co., LTD, Changsha 410014, P. R. China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Lu
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicine, Central South University, Changsha 410083, P. R. China tel: +86 731 8830831; fax: +86 731 8830831.
authors.forename: Yong-Huan
authors.initials: YH
authors.lastname: Yun
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicine, Central South University, Changsha 410083, P. R. China tel: +86 731 8830831; fax: +86 731 8830831.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Huang
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicine, Central South University, Changsha 410083, P. R. China tel: +86 731 8830831; fax: +86 731 8830831. yizeng_liang@263.net.
authors.forename: Yi-Zeng
authors.initials: YZ
authors.lastname: Liang
keywords: Applicability domain; Model disturbance index; Outlier comparison; Quantitative structure-activity relationship; Retention index