| 研究実績の概要 |
We established a high-throughput chemical-genetic screening platform to functionally annotate large compound collections in a rapid and systematic manner using next generation sequencing. Furthermore, we assembled a computational platform for functionally annotating compounds to specific biological processes and pathways. By FY2016, we analyzed ~10,000 compounds from the RIKEN Natural Product Depository (NPDepo). Finally, we applied our chemical-genetic pipeline to annotate 13,524 compounds in total by screening seven diverse compound collections: the RIKEN NPDepo; four collections from the National Cancer Institute’s Open Chemical Repository; a library of compounds from the National Institutes of Health Small Molecule Repository with a history of use in human clinical trials; and the GlaxoSmithKline kinase inhibitor collection. Based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality and annotated libraries’ functional diversity. The set of chemical-genetic profiles from a particular compound collection were classified into 17 distinct biological processes. Especially, glycosylation-, mitosis-, cell-polarity-, and vesicle-traffic-related functions were most frequently targeted, suggesting that these bioprocesses are more susceptible to chemical perturbation in yeast. Profiling revealed that the RIKEN NPDepo collection was the most functionally diverse collection, whereas the NCI natural products collection was the least diverse.
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