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Burst and Principal Components Analyses of MEA Data for 16 Chemicals Describe at Least Three Effects Classes.
Citation:
Mack, C., B. Linn, J. Turner, A. Johnstone, L. Burgoon, AND Tim Shafer. Burst and Principal Components Analyses of MEA Data for 16 Chemicals Describe at Least Three Effects Classes. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 40:75-85, (2013).
Impact/Purpose:
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Description:
Microelectrode arrays (MEAs) 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 (SVM) to classify chemical effects based on MEA data from 16 chemicals. Spontaneous frring 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 frrst 3 principal components accounted 65.6, 20.3, and 6.6% 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 3 chemical classes of increasing, decreasing or no change in activity with a mean accuracy of 82.6% 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 demonstrates that PCA and SVM offer promising approaches for classifying uncharacterized chemicals into effects categories that may provide information regarding mode of action.