scChemRISC: A Japanese consortium for sharing chemical risk information assessed by gene networks of human stem cells and machine learning
Center for iPS Research and Application, Kyoto University.
Aiming the achievement of efficient drug development, which costs several hundreds of million dollars per compound, we propose a novel alternative toxicity test towards the screening of safe medicines with high extrapolation efficiency to humans, reducing the development cost and time. In recent years, alternative methods using human differentiated cells have been developed, but the robustness of experimental method and the establishment of cell quality are challenging, indicating that it may take as long as a decade until the practical use. In the past, mouse embryonic toxicity test (EST) using ES cells and two kinds of differentiated cells has been used in Europe, but it has not been sufficient in terms of extrapolation efficiency to humans.
Here we propose a method which enables alternative toxicity tests to be carried out quickly, accurately, and at lower cost than conventional methods using human ES cells that are easy to control quality. We have recently developed a novel method "hEST" to predict three toxicity categories of chemicals such as neurotoxicity, genetic and non-genetic carcinogens with a prediction accuracy of 95% or more by machine learning of gene network using only human ES cells (Nucleic Acids Res. 2016). Inspired by this innovative technique, about 100 of Japanese toxicologists have organized a consortium, scChemRISC, where we will develop a gene expression database and an analysis system against various organ toxicity such as heart, nerve, liver, blood, etc. We have also introduced germ line stem cells such as MSCs to the system to further expand the testable chemicals.
Ultimately, tests using human iPS cells that exhibit donor diversity with less ethical issues will be conducted and must be verified the validity of iPS cell tests on the ES cell database. Once this project is accomplished, a low-cost, accurate and robust alternative toxicity testing method that reduces more than half the current animal study cost and time will be expected to contribute to our goal of highly safe drug development.