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A High Throughput Assay for Predicting Human Developmental Toxicity Using Human Embryonic Stem Cells and Metabolomics

机译:使用人胚胎干细胞和代谢组学预测人类发育毒性的高通量测定

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Metabolomic analyses of the response of three hES cell lines H1, H7, and H9 to a series of teratogen and non-teratogen drug treatments in order to generate a predictive biochemical model of developmental toxicity led to several major conclusions: (1) There were no metabolites unique to a single cell line. (2) MS-MS validation of the chemical structures was completed for a set of 28 statistically significant small molecule candidate biomarkers. (3) Few statistical differences in the abundance of secreted features were observed. (4) General metabolic competence of the three cell lines is similar. (5) Models trained with results from a single cell line were less likely to predict the other cell lines. (6) Models trained with data for the three cell lines performed the best, predicting teratogenicity with approx80percent accuracy across the three cell lines.
机译:三个HES细胞系H1,H7和H9对一系列致致致致致致致致致致致致致致致致致致致胎药物处理的代谢组分分析,以产生发育毒性的预测生化模型导致了几个主要结论:(1)没有单细胞系特有的代谢物。 (2)为一组28个统计学显着的小分子候选生物标志物完成化学结构的MS-MS验证。 (3)观察到分泌特征丰富的统计学差异很少。 (4)三种细胞系的一般代谢能力是相似的。 (5)由单个细胞系的结果训练的模型不太可能预测其他细胞系。 (6)培训的模型为三个细胞系进行了最佳,预测三个细胞系具有大约80%的致畸性。

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