StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells


An 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 predict adult toxicities 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. © 2022 The Author(s).

Authors Yamane J, Wada T, Otsuki H, Inomata K, Suzuki M, Hisaki T, Sekine S, Kouzuki H, Kobayashi K, Sone H, Yamashita JK, Osawa M, Saito MK, Fujibuchi W
Journal iScience
Publication Date 2022 Jul 15;25(7):104538
PubMed 35754715
PubMed Central PMC9218511
DOI 10.1016/j.isci.2022.104538

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