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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 undifferen...

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Autores principales: Yamane, Junko, Wada, Takumi, Otsuki, Hironori, Inomata, Koji, Suzuki, Mutsumi, Hisaki, Tomoka, Sekine, Shuichi, Kouzuki, Hirokazu, Kobayashi, Kenta, Sone, Hideko, Yamashita, Jun K., Osawa, Mitsujiro, Saito, Megumu K., Fujibuchi, Wataru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218511/
https://www.ncbi.nlm.nih.gov/pubmed/35754715
http://dx.doi.org/10.1016/j.isci.2022.104538
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author Yamane, Junko
Wada, Takumi
Otsuki, Hironori
Inomata, Koji
Suzuki, Mutsumi
Hisaki, Tomoka
Sekine, Shuichi
Kouzuki, Hirokazu
Kobayashi, Kenta
Sone, Hideko
Yamashita, Jun K.
Osawa, Mitsujiro
Saito, Megumu K.
Fujibuchi, Wataru
author_facet Yamane, Junko
Wada, Takumi
Otsuki, Hironori
Inomata, Koji
Suzuki, Mutsumi
Hisaki, Tomoka
Sekine, Shuichi
Kouzuki, Hirokazu
Kobayashi, Kenta
Sone, Hideko
Yamashita, Jun K.
Osawa, Mitsujiro
Saito, Megumu K.
Fujibuchi, Wataru
author_sort Yamane, Junko
collection PubMed
description 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.
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spelling pubmed-92185112022-06-24 StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells Yamane, Junko Wada, Takumi Otsuki, Hironori Inomata, Koji Suzuki, Mutsumi Hisaki, Tomoka Sekine, Shuichi Kouzuki, Hirokazu Kobayashi, Kenta Sone, Hideko Yamashita, Jun K. Osawa, Mitsujiro Saito, Megumu K. Fujibuchi, Wataru iScience Article 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. Elsevier 2022-06-06 /pmc/articles/PMC9218511/ /pubmed/35754715 http://dx.doi.org/10.1016/j.isci.2022.104538 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yamane, Junko
Wada, Takumi
Otsuki, Hironori
Inomata, Koji
Suzuki, Mutsumi
Hisaki, Tomoka
Sekine, Shuichi
Kouzuki, Hirokazu
Kobayashi, Kenta
Sone, Hideko
Yamashita, Jun K.
Osawa, Mitsujiro
Saito, Megumu K.
Fujibuchi, Wataru
StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title_full StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title_fullStr StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title_full_unstemmed StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title_short StemPanTox: A fast and wide-target drug assessment system for tailor-made safety evaluations using personalized iPS cells
title_sort stempantox: a fast and wide-target drug assessment system for tailor-made safety evaluations using personalized ips cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218511/
https://www.ncbi.nlm.nih.gov/pubmed/35754715
http://dx.doi.org/10.1016/j.isci.2022.104538
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