title: Clustering and rule-based classifications of chemical structures evaluated in the biological activity space.
abstract: Classification methods for data sets of molecules according to their chemical structure were evaluated for their biological relevance, including rule-based, scaffold-oriented classification methods and clustering based on molecular descriptors. Three data sets resulting from uniformly determined in vitro biological profiling experiments were classified according to their chemical structures, and the results were compared in a Pareto analysis with the number of classes and their average spread in the profile space as two concurrent objectives which were to be minimized. It has been found that no classification method is overall superior to all other studied methods, but there is a general trend that rule-based, scaffold-oriented methods are the better choice if classes with homogeneous biological activity are required, but a large number of clusters can be tolerated. On the other hand, clustering based on chemical fingerprints is superior if fewer and larger classes are required, and some loss of homogeneity in biological activity can be accepted.
authors.affiliation: Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. ansgar.schuffenhauer@novartis.com
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schuffenhauer
authors.forename: Nathan
authors.initials: N
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Ertl
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Jenkins
authors.forename: Paul
authors.initials: P
authors.lastname: Selzer
authors.forename: Jacques
authors.initials: J
authors.lastname: Hamon
mesh_terms: D016000:Cluster Analysis; D019295:Computational Biology / Q000706:statistics & numerical data*; D030541:Databases, Genetic; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000145:classification*; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations