Linking novel bioactive compounds to their targets and pathways using chemical genomics and morphological profiling

• Project/Area Number: 15H04483
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied microbiology
• Research Institution: Institute of Physical and Chemical Research
• 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)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
• Keywords: chemical genomics / morphological profiling / yeast / target identification

Outline of Final Research Achievements

Combining chemical genomics profiling based on genetic interactions and morphological profiling using a sophisticated image-processing program, CalMorph, we developed a multi-dimensional strategy for linking novel bioactive compounds to their targets and pathways. 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. Finally, we applied our chemical-genomic/morphological profiling pipeline to annotate 13,524 compounds in total by screening seven diverse compound collections including the RIKEN NPDepo library.

Research Products

• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] ミネソタ大学(米国)
• [Int'l Joint Research] ミネソタ大学(米国)
• [Int'l Joint Research] トロント大学(カナダ)
• [Int'l Joint Research] ストラスブール大学/リヨン大学(フランス)
• [Int'l Joint Research] University of Minnesota(米国)
• [Journal Article] MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action (2018)
  • Author(s): Nelson J, Simpkins SW, Safizadeh H, Li SC, Piotrowski JS, Hirano H, Yashiroda Y, Osada H, Yoshida M, Boone C, Myers CL.
  • Journal Title: Bioinformatics Volume: 34 Issue: 7 Pages: 1251-1252
  • DOI: 10.1093/bioinformatics/btx732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Global study of holistic morphological effectors in the budding yeast Saccharomyces cerevisiae (2018)
  • Author(s): Suzuki G, Wang Y, Kubo K, Hirata E, Ohnuki S, Ohya Y
  • Journal Title: BMC Genomics Volume: 19 Issue: 1 Pages: 149-149
  • DOI: 10.1186/s12864-018-4526-z
  • Peer Reviewed / Open Access
• [Journal Article] Testing the neutral hypothesis of phenotypic evolution (2018)
  • Author(s): Ho WC, Ohya Y, Zhang J
  • Journal Title: Proc Natl Acad Sci U S A Volume: 114 Issue: 46 Pages: 12219-12224
  • DOI: 10.1073/pnas.1710351114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional annotation of chemical libraries across diverse biological processes. (2017)
  • Author(s): Piotrowski JS, Li SC, Deshpande R.......Shirahige K,......Boone C.
  • Journal Title: Nat Chem Biol. Volume: 13 Issue: 9 Pages: 982-993
  • DOI: 10.1038/nchembio.2436
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Phenotypic diagnosis of lineage and differentiation during sake yeast breeding (2017)
  • Author(s): Shinsuke Ohnuki, Hiroki Okada, Anne Friedrich, Yoichiro Kanno, Tetsuya Goshima, Hirokazu Hasuda, Masaaki Inahashi, Naoto Okazaki, Hiroyasu Tamura, Ryo Nakamura, Dai Hirata, Hisashi Fukuda, Hitoshi Shimoi, Katsuhiko Kitamoto, Daisuke Watanabe, Joseph Schacherer, Takeshi Akao, Yoshikazu Ohya
  • Journal Title: G3 (Bethesda) Volume: 7 Issue: 8 Pages: 2807-2820
  • DOI: 10.1534/g3.117.044099
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Systematic analysis of Ca2+ homoeostasis in Saccharomyces cerevisiae based on chemical-genetic interaction profiles (2017)
  • Author(s): Farzan Ghanegolmohammadi, Mitsunori Yoshida, Shinsuke Ohnuki, Yuko Sukegawa, Hiroki Okada, Keisuke Obara, Akio Kihara, Kuninori Suzuki, Tetsuya Kojima, Nozomu Yachie, Dai Hirata, Yoshikazu Ohya
  • Journal Title: Mol. Biol. Cell Volume: 28 Issue: 23 Pages: 3415-3427
  • DOI: 10.1091/mbc.e17-04-0216
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Dual Activity Responsible for the Elongation and Branching of β-(1,3)-Glucan in the Fungal Cell Wall. (2017)
  • 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
  • Journal Title: MBio Volume: 8 Issue: 3
  • DOI: 10.1128/mbio.00619-17
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Exploring genetic suppression interactions on a global scale (2016)
  • Author(s): van Leeuwen J, Pons C, Mellor JC, Yamaguchi TN, Friesen H, ..., and Boone C.
  • Journal Title: Science Volume: 354 Issue: 6312
  • DOI: 10.1126/science.aag0839
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A global genetic interaction network maps a wiring diagram of cellular function (2016)
  • Author(s): Costanzo M, VanderSluis B, Koch EN, Baryshnikova A, Pons C, ..., and Boone C.
  • Journal Title: Science Volume: 353 Issue: 6306
  • DOI: 10.1126/science.aaf1420
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Examination and Disruption of the Yeast Cell Wall (2016)
  • Author(s): Okada H, Kono K, Neiman AM, Ohya Y
  • Journal Title: Cold Spring Harb Protoc. Volume: 2016 Issue: 8 Pages: 078659-078659
  • DOI: 10.1101/pdb.top078659
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fluorescent Labeling of Yeast Cell Wall Components. (2016)
  • Author(s): Okada H, Ohya Y
  • Journal Title: Cold Spring Harb Protoc. Volume: 2016 Issue: 8 Pages: 085241-085241
  • DOI: 10.1101/pdb.prot085241
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exploiting Single-Cell Quantitative Data to Map Genetic Variants Having Probabilistic Effects. (2016)
  • Author(s): Chuffart F, Richard M, Jost D, Burny C, Duplus-Bottin H, Ohya Y, Yvert G.
  • Journal Title: PLOS Genetics Volume: 12 Issue: 8 Pages: e1006213-e1006213
  • DOI: 10.1371/journal.pgen.1006213
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of a mutation causing a defective spindle assembly checkpoint in high ethyl caproate-producing sake yeast strain K1801. (2016)
  • Author(s): Goshima T, Nakamura R, Kume K, Okada H, Ichikawa E, Tamura H, Hasuda H, Inahashi M, Okazaki N, Akao T, Shimoi H, Mizunuma M, Ohya Y, Hirata D.
  • Journal Title: Biosci Biotechnol Biochem. Volume: 80 Issue: 8 Pages: 1657-62
  • DOI: 10.1080/09168451.2016.1184963
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Large-Scale Survey of Intraspecific Fitness and Cell Morphology Variation in a Protoploid Yeast Species. (2016)
  • Author(s): Jung PP, Sigwalt A, Ohnuki S, de Montigny J, Ohya Y, Schacherer J.
  • Journal Title: G3 Volume: 6 Issue: 4 Pages: 1063-71
  • DOI: 10.1534/g3.115.026682
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Plant-derived antifungal agent poacic acid targets β-1,3-glucan (2015)
  • Author(s): Piotrowski JS, Okada H, Lu F, Li SC, Hinchman L, Ranjan A, Smith DL, Higbee AJ, Ulbrich A, Coon JJ, Deshpande R, Bukhman YV, McIlwain S, Ong IM, Myers CL, Boone C, Landick R, Ralph J, Kabbage M, Ohya Y
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Issue: 12
  • DOI: 10.1073/pnas.1410400112
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chemical genomic profiling via barcode sequencing to predict compound mode of action. (2015)
  • Author(s): Piotrowski JS, Simpkins SW, Li SC, Deshpande R, McIlwain SJ, Ong IM, Myers CL, Boone C, Andersen RJ.
  • Journal Title: Methods Mol Biol Volume: 1263 Pages: 299-318
  • DOI: 10.1007/978-1-4939-2269-7_23
  • ISBN: 9781493922680, 9781493922697
  • Open Access / Int'l Joint Research
• [Journal Article] Controlling microbial contamination during hydrolysis of AFEX-pretreated corn stover and switchgrass: effects on hydrolysate composition, microbial response and fermentation. (2015)
  • Author(s): Serate J, Xie D, Pohlmann E, Donald C Jr, Shabani M, Hinchman L, Higbee A, Mcgee M, La Reau A, Klinger GE, Li S, Myers CL, Boone C, Bates DM, Cavalier D, Eilert D, Oates LG, Sanford G, Sato TK, Dale B, Landick R, Piotrowski J, Ong RG, Zhang Y.
  • Journal Title: Biotechnol Biofuels Volume: 8 Issue: 1 Pages: 180-180
  • DOI: 10.1186/s13068-015-0356-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Profiling of the effects of antifungal agents on yeast cells based on morphometric analysis. (2015)
  • Author(s): Gebre AA, Okada H, Kim C, Kubo K, Ohnuki S, Ohya Y.
  • Journal Title: FEMS Yeast Res. Volume: 15 Issue: 5 Pages: fov040-fov040
  • DOI: 10.1093/femsyr/fov040
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Mapping Chemical-Genetic Interactions to Link Bioactive Compounds to Cellular Targets (2018)
  • Author(s): Charles Boone
  • Organizer: 新学術領域研究「化学コミュニケーションのフロンティア」第２回公開シンポジウム
  • Invited
• [Presentation] A global genetic interaction network maps a wiring diagram of cellular function (2017)
  • Author(s): Charles Boone
  • Organizer: Opportunities and Challenges of Exploiting Synthetic Lethality in Cancer
  • Place of Presentation: 米国 サンディエゴ
  • Year and Date: 2017-01-04
  • Int'l Joint Research / Invited
• [Presentation] Target Identification Using an Integrated Chemical Genetic Approach (2017)
  • Author(s): Sheena Li, Charles Boone
  • Organizer: CIFAR meeting
  • Int'l Joint Research
• [Presentation] Mapping Genetic Networks on a Global Scale (2017)
  • Author(s): Charles Boone
  • Organizer: From Genetic Networks to a Cellular Wiring Diagram
  • Int'l Joint Research / Invited
• [Presentation] High-dimensional and single-cell phenotyping in Saccharomyces cerevisiae: Rational selection of the morphological parameters (2017)
  • Author(s): Yoshikazu Ohya
  • Organizer: CIFAR Meeting
  • Int'l Joint Research / Invited
• [Presentation] The book of yeast morphology is written in the language of mathematics (2017)
  • Author(s): Yoshikazu Ohya
  • Organizer: Gene, genom and beyond
  • Int'l Joint Research / Invited
• [Presentation] 酵母の細胞壁研究の魅力 (2017)
  • Author(s): 大矢禎一
  • Organizer: 日本植物学会シンポジウム
  • Invited
• [Presentation] 出芽酵母の形態表現型に強い影響を与える遺伝子変異株の網羅的解析 (2017)
  • Author(s): 鈴木吾大、王洋、大貫慎輔、大矢禎一
  • Organizer: 第50回酵母遺伝学フォーラム
• [Presentation] 高次元形態表現型に基づく遺伝子機能特異的表現型自動抽出法の開発 (2017)
  • Author(s): 大貫慎輔、徐聴涛、大矢禎一
  • Organizer: 第40回日本分子生物学会年会
• [Presentation] A global genetic interaction network maps a wiring diagram of cellular function (2017)
  • Author(s): Charles Boone
  • Organizer: 9th HiHA International Workshop; Toward a comprehensive understanding of a global genetic network within a cell
  • Place of Presentation: 広島大学（広島県東広島市）
  • Int'l Joint Research / Invited
• [Presentation] High-dimensional and -single cell phenotyping in Saccharomyces cerevisiae (2017)
  • Author(s): Yoshikazu Ohya
  • Organizer: 9th HiHA International Workshop; Toward a comprehensive understanding of a global genetic network within a cell
  • Place of Presentation: 広島大学（広島県東広島市）
  • Int'l Joint Research / Invited
• [Presentation] Global Analysis of Genetic Interaction Networks in Yeast (2016)
  • Author(s): Charles Boone
  • Organizer: Human and Mammalian Genetics and Genomics: The 57th McKusick Short Course
  • Place of Presentation: 米国 バーハーバー
  • Year and Date: 2016-07-17
  • Int'l Joint Research / Invited
• [Presentation] Single Cell Phenotyping of Sake Yeast (2016)
  • Author(s): 大矢禎一
  • Organizer: バイオイメージ・インフォマティクスワークショップ 2016
  • Place of Presentation: 大阪大学（大阪府吹田市）
  • Year and Date: 2016-06-22
• [Presentation] Exploring Functional Genetic Suppression Interactions on a Global Scale (2016)
  • Author(s): Charles Boone
  • Organizer: CIFAR meeting
  • Place of Presentation: カナダ トロント
  • Year and Date: 2016-04-15
  • Int'l Joint Research / Invited
• [Presentation] Application of Single Cell Phenomics in Chemical Genomics (2016)
  • Author(s): Yoshikazu Ohya
  • Organizer: CIFAR meeting
  • Place of Presentation: カナダ トロント
  • Year and Date: 2016-04-15
  • Int'l Joint Research / Invited
• [Presentation] 清酒酵母の単細胞フェノタイピング (2016)
  • Author(s): 大矢禎一
  • Organizer: 酵母細胞研究会
  • Place of Presentation: 東京大学（東京都文京区）
  • Invited
• [Presentation] A cell cycle checkpoint to insure the integrity of the cell wall synthesis (2016)
  • Author(s): Yoshikazu Ohya
  • Organizer: LIISAIB
  • Place of Presentation: アルゼンチン コルドバ
  • Int'l Joint Research / Invited
• [Presentation] 清酒酵母今昔 (2016)
  • Author(s): 大矢禎一
  • Organizer: 日本酒史学会
  • Place of Presentation: 東京大学（千葉県柏市）
  • Invited
• [Presentation] New antifungal agents that inhibit cell wall synthesis (2015)
  • Author(s): Yoshikazu Ohya
  • Organizer: Fungal Cell Wall 2015
  • Place of Presentation: Paris, France
  • Year and Date: 2015-10-26
  • Int'l Joint Research / Invited
• [Presentation] Functional annotation of biological processes targeted by chemical libraries (2015)
  • Author(s): Sheena Li, Charlie Boone
  • Organizer: 27° International conference on yeast genetics and molecular biology
  • Place of Presentation: Levico Terme, Italy
  • Year and Date: 2015-09-10
  • Int'l Joint Research
• [Presentation] 化学遺伝学と形態学のプロファイリング解析による細胞壁合成経路を標的にする抗真菌剤の探索 (2015)
  • Author(s): 久保 佳蓮,岡田 啓希,Abraham Abrera,Sheena Li,Jeff Piotrowski,Chad Myers,八代田 陽子,Charlie Boone, 吉田 稔,長田 裕之,斎藤 臣雄,大矢 禎一
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2015-07-02
• [Presentation] High-dimensional morphological phenotyping in Saccharomyces cerevisiae (2015)
  • Author(s): Yoshikazu Ohya
  • Organizer: Annual Meeting of Microbiology in Korea
  • Place of Presentation: Changwon, Korea
  • Year and Date: 2015-04-15
  • Int'l Joint Research / Invited
• [Book] 第9章 新しい創薬ツールとしての出芽酵母（「酵母菌・麹菌・乳酸菌の産業応用展開」） (2018)
  • Author(s): 久保佳蓮、大矢禎一（五味勝也、阿部敬悦・監修）
  • Total Pages: 264
  • Publisher: シーエムシー出版
  • ISBN: 9784781313177
• [Remarks] 化合物の標的機能を決定するツールを開発－酵母の化学遺伝学アプローチで化合物の標的予測／同定が迅速に－
  • URL: http://www.riken.jp/pr/press/2017/20170725_1/
• [Remarks] 植物由来の次世代型農薬へ
  • URL: http://www.k.u-tokyo.ac.jp/info/entry/22_entry383/