Journal Article Prediction of developmental chemical toxicity based on gene networks of human embryonic stem cells.

Yamane, Junko  ,  Aburatani, Sachiyo  ,  Imanishi, Satoshi  ,  Akanuma, Hiromi  ,  Nagano, Reiko  ,  Kato, Tsuyoshi  ,  Sone, Hideko  ,  Ohsako, Seiichiroh  ,  Fujibuchi, Wataru

2016-05-20 , Oxford University Press
ES細胞と遺伝子ネットワークを用いた、高精度の化合物毒性予測システムの構築. 京都大学プレスリリース. 2016-06-14.
Predictive toxicology using stem cells or their derived tissues has gained increasing importance in biomedical and pharmaceutical research. Here, we show that toxicity category prediction by support vector machines (SVMs), which uses qRT-PCR data from 20 categorized chemicals based on a human embryonic stem cell (hESC) system, is improved by the adoption of gene networks, in which network edge weights are added as feature vectors when noisy qRT-PCR data fail to make accurate predictions. The accuracies of our system were 97. 5-100% for three toxicity categories: neurotoxins (NTs), genotoxic carcinogens (GCs) and non-genotoxic carcinogens (NGCs). For two uncategorized chemicals, bisphenol-A and permethrin, our system yielded reasonable results: bisphenol-A was categorized as an NGC, and permethrin was categorized as an NT; both predictions were supported by recently published papers. Our study has two important features: (i) as the first study to employ gene networks without using conventional quantitative structure-activity relationships (QSARs) as input data for SVMs to analyze toxicogenomics data in an hESC validation system, it uses additional information of gene-to-gene interactions to significantly increase prediction accuracies for noisy gene expression data; and (ii) using only undifferentiated hESCs, our study has considerable potential to predict late-onset chemical toxicities, including abnormalities that occur during embryonic development.

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