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

ABSTRACT: 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.

SUBMITTER: Yamane J

PROVIDER: S-EPMC9218511 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Organic matter management is key to sustain ecosystem services provided by soils. However, it is rarely considered in a holistic view, considering local resources, agro-environmental effects and harmonization with farmers' needs. Organic inputs, like compost and biochar, could represent a sustainable solution to massive current challenges associated to the intensification of agriculture, in particular for tropical regions. Here we assess the potential of agricultural residues as a resource for farmer communities in southwestern India to reduce their dependency on external inputs and sustain ecosystem services. We propose a novel joint evaluation of farmers' aspirations together with agro-environmental effects of organic inputs on soils. Our soil quality evaluation showed that biochar alone or with compost did not improve unilaterally soils in the tropics (Anthroposol, Ferralsol and Vertisol). Many organic inputs led to an initial decrease in water-holding capacities of control soils (-27.3%: coconut shell biochar with compost on Anthroposol). Responses to organic matter inputs for carbon were strongest for Ferralsols (+33.4% with rice husk biochar), and mostly positive for Anthroposols and Vertisols (+12.5% to +13.8% respectively). Soil pH responses were surprisingly negative for Ferralsols and only positive if biochar was applied alone (between -5.6% to +1.9%). For Anthroposols and Vertisols, highest increases were achieved with rice husk biochar + vermicomposts (+7.2% and +5.2% respectively). Our socio-economic evaluation showed that farmers with a stronger economical position showed greater interest towards technology like biochar (factor 1.3 to 1.6 higher for farmers cultivating Anthroposols and/or Vertisols compared to Ferralsols), while poorer farmers more skepticism, which may lead to an increased economical gap within rural communities if technologies are not implemented with long-term guidance. These results advocate for an interdisciplinary evaluation of agricultural technology prior to its implementation as a development tool in the field.

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

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