文章基本信息

标题：StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
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作者：Junko Yamane ; Takumi Wada ; Hironori Otsuki 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：7
页码：1-23
DOI：10.1016/j.isci.2022.104538
语种：English
出版社：Elsevier
摘要：SummaryAn alternative model that reliably predicts human-specific toxicity is necessary because the translatability of effects on animal models for human disease is limited to context. Previously, we developed a method that accurately predicts developmental toxicity based on the gene networks of undifferentiated human embryonic stem (ES) cells. Here, we advanced this method to predictadulttoxicities of 24 chemicals in six categories (neurotoxins, cardiotoxins, hepatotoxins, two types of nephrotoxins, and non-genotoxic carcinogens) and achieved high predictability (AUC = 0.90–1.00) in all categories. Moreover, we screened for an induced pluripotent stem (iPS) cell line to predict the toxicities based on the gene networks of iPS cells using transfer learning of the gene networks of ES cells, and predicted toxicities in four categories (neurotoxins, hepatotoxins, glomerular nephrotoxins, and non-genotoxic carcinogens) with high performance (AUC = 0.82–0.99). This method holds promise for tailor-made safety evaluations using personalized iPS cells.Graphical abstractDisplay OmittedHighlights•Undifferentiated human embryonic stem cells can detect adult chemical toxicities•Toxicity predictions using gene expression networks achieve high predictability•Transfer learning from ES to iPS cells ameliorates the ethical issues•StemPanTox may contribute to toxicity assessment using personalized iPS cellsBiological sciences; Toxicology; Computational toxicology; Cell biology; Bioinformatics