Dataset Information

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.

ABSTRACT: Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their associated quantitative phenotypic features most predictive of in vivo pulmonotoxicity. This approach is called "High-throughput In vitro Phenotypic Profiling for Toxicity Prediction" (HIPPTox). We found that the resulting assay based on two phenotypic features of a human bronchial epithelial cell line, BEAS-2B, can accurately classify 33 reference chemicals with human pulmonotoxicity information (88.8% balance accuracy, 84.6% sensitivity, and 93.0% specificity). In comparison, the predictivity of a standard cell-viability assay on the same set of chemicals is much lower (77.1% balanced accuracy, 84.6% sensitivity, and 69.5% specificity). We also used the assay to evaluate 17 additional test chemicals with unknown/unclear human pulmonotoxicity, and experimentally confirmed that many of the pulmonotoxic reference and predicted-positive test chemicals induce DNA strand breaks and/or activation of the DNA-damage response (DDR) pathway. Therefore, HIPPTox helps us to uncover these common modes-of-action of pulmonotoxic chemicals. HIPPTox may also be applied to other cell types or models, and accelerate the development of predictive in vitro assays for other cell-type- or organ-specific toxicities.

SUBMITTER: Lee JJ

PROVIDER: S-EPMC6002469 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.

Lee Jia-Ying Joey JJ Miller James Alastair JA Basu Sreetama S Kee Ting-Zhen Vanessa TV Loo Lit-Hsin LH

Archives of toxicology 20180428 6

Human lungs are susceptible to the toxicity induced by soluble xenobiotics. However, the direct cellular effects of many pulmonotoxic chemicals are not always clear, and thus, a general in vitro assay for testing pulmonotoxicity applicable to a wide variety of chemicals is not currently available. Here, we report a study that uses high-throughput imaging and artificial intelligence to build an in vitro pulmonotoxicity assay by automatically comparing and selecting human lung-cell lines and their ...[more]

PMID: 29705884

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Dataset Information

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.

Publications

Building predictive in vitro pulmonary toxicity assays using high-throughput imaging and artificial intelligence.

Similar Datasets

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