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DOI10.1016/j.neuro.2013.11.008
Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes
Mack, Cina M.1; Lin, Bryant J.2; Turner, James D.3; Johnstone, Andrew F. M.1; Burgoon, Lyle D.4; Shafer, Timothy J.1
发表日期2014
ISSN0161-813X
卷号40页码:75-85
英文摘要

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 GABA(A) 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. Published by Elsevier Inc.


英文关键词Neurotoxicity screening;In vitro;Chemical fingerprinting
语种英语
WOS记录号WOS:000331027600010
来源期刊NEUROTOXICOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/59157
作者单位1.US EPA, ORD, NHEERL, Res Triangle Pk, NC 27711 USA;
2.NC Sch Sci & Math, Durham, NC USA;
3.N Carolina State Univ, Raleigh, NC 27695 USA;
4.US EPA, ORD, NCEA, Durham, NC USA
推荐引用方式
GB/T 7714
Mack, Cina M.,Lin, Bryant J.,Turner, James D.,et al. Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes[J]. 美国环保署,2014,40:75-85.
APA Mack, Cina M.,Lin, Bryant J.,Turner, James D.,Johnstone, Andrew F. M.,Burgoon, Lyle D.,&Shafer, Timothy J..(2014).Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes.NEUROTOXICOLOGY,40,75-85.
MLA Mack, Cina M.,et al."Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes".NEUROTOXICOLOGY 40(2014):75-85.
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