A data mining approach to in vivo classification of psychopharmacological drugs.
Data mining is a powerful bioinformatics strategy that has been successfully applied in vitro to screen for gene-expression profiles predicting toxicological or carcinogenic response ('class predictors'). In this report we used a data mining algorithm named Pattern Array (PA) in vivo to analyze mouse open-field behavior and characterize the psychopharmacological effects of three drug classes--psychomotor stimulant, opioid, and psychotomimetic. PA represents rodent movement with approximately 100,000 complex patterns, defined as multiple combinations of several ethologically relevant variables, and mines them for those that maximize any effect of interest, such as the difference between drug classes. We show that PA can discover behavioral predictors of all three drug classes, thus developing a reliable drug-classification scheme in small group sizes. The discovered predictors showed orderly dose dependency despite being explicitly mined only for class differences, with the high doses scoring 4-10 standard deviations from the vehicle group. Furthermore, these predictors correctly classified in a dose-dependent manner four 'unknown' drugs (ie that were not used in the training process), and scored a mixture of a psychomotor stimulant and an opioid as being intermediate between these two classes. The isolated behaviors were highly heritable (h(2)>50%) and replicable as determined in 10 inbred strains across three laboratories. PA can in principle be applied for mining behaviors predicting additional properties, such as within-class differences between drugs and within-drug dose-response, all of which can be measured automatically in a single session per animal in an open-field arena, suggesting a high potential as a tool in psychotherapeutic drug discovery.
Kafkafi
Neri
N
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA. nkafkafi@mprc.umaryland.edu
Yekutieli
Daniel
D
Elmer
Greg I
GI
D000465:Algorithms; D000701:Analgesics, Opioid / Q000145:classification* / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000145:classification*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006213:Hallucinogens / Q000145:classification* / Q000494:pharmacology; D008297:Male; D008490:Medical Informatics / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009068:Movement / Q000187:drug effects*; D010363:Pattern Recognition, Automated; D019655:Quantitative Trait, Heritable
D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D006213:Hallucinogens