title: Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes.
abstract: Microelectrode arrays (MEAs) can be used to detect drug and chemical induced changes in neuronal network function and have been used for neurotoxicity screening. As a proof-of-concept, the current study assessed the utility of analytical "fingerprinting" using principal components analysis (PCA) and chemical class prediction using support vector machines (SVMs) to classify chemical effects based on MEA data from 16 chemicals. Spontaneous firing rate in primary cortical cultures was increased by bicuculline (BIC), lindane (LND), RDX and picrotoxin (PTX); not changed by nicotine (NIC), acetaminophen (ACE), and glyphosate (GLY); and decreased by muscimol (MUS), verapamil (VER), fipronil (FIP), fluoxetine (FLU), chlorpyrifos oxon (CPO), domoic acid (DA), deltamethrin (DELT) and dimethyl phthalate (DMP). PCA was performed on mean firing rate, bursting parameters and synchrony data for concentrations above each chemical's EC50 for mean firing rate. The first three principal components accounted for 67.5, 19.7, and 6.9% of the data variability and were used to identify separation between chemical classes visually through spatial proximity. In the PCA, there was clear separation of GABAA antagonists BIC, LND, and RDX from other chemicals. For the SVM prediction model, the experiments were classified into the three chemical classes of increasing, decreasing or no change in activity with a mean accuracy of 83.8% under a radial kernel with 10-fold cross-validation. The separation of different chemical classes through PCA and high prediction accuracy in SVM of a small dataset indicates that MEA data may be useful for separating chemicals into effects classes using these or other related approaches.
authors: NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States.
authors: Cina M
authors: CM
authors: Mack
authors: N.C. School of Science and Mathethmatics, Durham, NC, United States.
authors: Bryant J
authors: BJ
authors: Lin
authors: North Carolina State University, Raleigh, NC, United States.
authors: James D
authors: JD
authors: Turner
authors: NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States.
authors: Andrew F M
authors: AF
authors: Johnstone
authors: NCEA, ORD, U.S. Environmental Protection Agency, Research Triangle Park, Durham, NC, United States.
authors: Lyle D
authors: LD
authors: Burgoon
authors: NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States. Electronic address: Shafer.tim@epa.gov.
authors: Timothy J
authors: TJ
authors: Shafer
mesh_terms: D000082:Acetaminophen / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003627:Data Interpretation, Statistical; D005473:Fluoxetine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008839:Microelectrodes; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology; D025341:Principal Component Analysis; D051381:Rats; D020318:Rats, Long-Evans; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018756:GABA Antagonists; D010575:Pesticides; D005473:Fluoxetine; D009118:Muscimol; D000082:Acetaminophen; D009538:Nicotine; D014700:Verapamil; C012301:domoic acid; D007608:Kainic Acid
keywords: Chemical fingerprinting; In vitro; Neurotoxicity screening