title: Effect of selection of molecular descriptors on the prediction of blood-brain barrier penetrating and nonpenetrating agents by statistical learning methods.
abstract: The ability or inability of a drug to penetrate into the brain is a key consideration in drug design. Drugs for treating central nervous system (CNS) disorders need to be able to penetrate the blood-brain barrier (BBB). BBB nonpenetration is desirable for non-CNS-targeting drugs to minimize potential CNS-related side effects. Computational methods have been employed for the prediction of BBB-penetrating (BBB+) and -nonpenetrating (BBB-) agents at impressive accuracies of 75-92% and 60-80%, respectively. However, the majority of these studies give a substantially lower BBB- accuracy, and thus overall accuracy, than the BBB+ accuracy. This work examined whether proper selection of molecular descriptors can improve both the BBB- and the overall accuracies of statistical learning methods. The methods tested include logistic regression, linear discriminate analysis, k nearest neighbor, C4.5 decision tree, probabilistic neural network, and support vector machine. Molecular descriptors were selected by using a feature selection method, recursive feature elimination (RFE). Results by using 415 BBB+ and BBB- agents show that RFE substantially improves both the BBB- and the overall accuracy for all of the methods studied. This suggests that statistical learning methods combined with proper feature selection is potentially useful for facilitating a more balanced and improved prediction of BBB+ and BBB- agents.
authors.affiliation: Bioinformatics and Drug Design Group, Department of Computational Science, National University of Singapore, Blk SOC1, Level 7, 3 Science Drive 2, Singapore 117543, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Yap
authors.forename: Choong Yong
authors.initials: CY
authors.lastname: Ung
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Cao
authors.forename: Yu Zong
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D001185:Artificial Intelligence; D001812:Blood-Brain Barrier / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D015195:Drug Design; D015233:Models, Statistical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations