title: Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2 inhibition: importance of the quality of the dataset.
abstract: The purpose of this study was to explore the use of detailed biological data in combination with a statistical learning method for predicting the CYP1A2 and CYP2D6 inhibition. Data were extracted from the Aureus-Pharma highly structured databases which contain precise measures and detailed experimental protocol concerning the inhibition of the two cytochromes. The methodology used was Recursive Partitioning, an easy and quick method to implement. The building of models was preceded by the evaluation of the chemical space covered by the datasets. The descriptors used are available in the MOE software suite. The models reached at least 80% of Accuracy and often exceeded this percentage for the Sensitivity (Recall), Specificity, and Precision parameters. CYP2D6 datasets provided 11 models with Accuracy over 80%, while CYP1A2 datasets counted 5 high-accuracy models. Our models can be useful to predict the ADME properties during the drug discovery process and are indicated for high-throughput screening.
authors.affiliation: Laboratoire de Physico-Chimie Informatique, Facultés Universitaires Notre-Dame de la Paix, 61 rue de Bruxelles, B-5000 Namur, Belgium. julien.burton@fundp.ac.be
authors.forename: Julien
authors.initials: J
authors.lastname: Burton
authors.forename: Ismail
authors.initials: I
authors.lastname: Ijjaali
authors.forename: Olivier
authors.initials: O
authors.lastname: Barberan
authors.forename: François
authors.initials: F
authors.lastname: Petitet
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Vercauteren
authors.forename: André
authors.initials: A
authors.lastname: Michel
mesh_terms: D001185:Artificial Intelligence; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D012680:Sensitivity and Specificity; D012984:Software
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6