2017 Fiscal Year Annual Research Report
Linking novel bioactive compounds to their targets and pathways using chemical genomics and morphological profiling
| Project/Area Number |
15H04483
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
BOONE CHARLES 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (70601342)
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| Co-Investigator(Kenkyū-buntansha) |
大矢 禎一 東京大学, 大学院新領域創成科学研究科, 教授 (20183767)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | chemical genomics / morphological profiling / yeast / target identification |
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| Outline of Annual Research Achievements |
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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| Research Progress Status |
29年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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[Journal Article] MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action2018
Author(s)
Nelson J, Simpkins SW, Safizadeh H, Li SC, Piotrowski JS, Hirano H, Yashiroda Y, Osada H, Yoshida M, Boone C, Myers CL.
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Journal Title
Bioinformatics
Volume: 34
Pages: 1251-1252
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Phenotypic Diagnosis of Lineage and Differentiation During Sake Yeast Breeding2017
Author(s)
Ohnuki S, Okada H, Friedrich A, Kanno Y, Goshima T, Hasuda H, Inahashi M, Okazaki N, Tamura H, Nakamura R, Hirata D, Fukuda H, Shimoi H, Kitamoto K, Watanabe D, Schacherer J, Akao T, Ohya Y.
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Journal Title
G3 (Bethesda)
Volume: 7
Pages: 2807-2820
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Systematic analysis of Ca2+ homeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles.2017
Author(s)
Ghanegolmohammadi F, Yoshida M, Ohnuki S, Sukegawa Y, Okada H, Obara K, Kihara A, Suzuki K, Kojima T, Yachie N, Hirata D, Ohya Y.
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Journal Title
Mol Biol Cell
Volume: 28
Pages: 3415-3427
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The Dual Activity Responsible for the Elongation and Branching of β-(1,3)-Glucan in the Fungal Cell Wall2017
Author(s)
Aimanianda V, Simenel C, Garnaud C, Clavaud C, Tada R, Barbin L, Mouyna I, Heddergott C, Popolo L, Ohya Y, Delepierre M, Latge JP.
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Journal Title
MBio
Volume: 8
Pages: e00619-17
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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