A technology to measure personal interactomes

• Project/Area Number: 18H02428
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yachie Nozomu 東京大学, 先端科学技術研究センター, 客員准教授 (60636801)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: タンパク質間相互作用 / インタラクトーム / 酵母遺伝学 / DNAバーコード / 超並列シークエンシング / 次世代シークエンシング

Outline of Final Research Achievements

Human disorders and cancers are rarely interpreted by a single gene defect but rather by a malfunction of the cellular network. The recent deep sequencing-based screening methods have enabled high-throughput identification of human protein interaction maps. Furthermore, computational studies have shown that phenotypic prediction of mutations can be improved using cellular network information. This study aimed to develop a personal interactome technology using a high-throughput interactome screening method BFG-Y2H (barcode fusion genetics-yeast two-hybrid) that we have established previously.

Academic Significance and Societal Importance of the Research Achievements

ゲノム変異情報をヒトのリファレンスインタラクトームにマッピングすることで病態予測や予後予測の精度が向上することが示されている。また疾患関連変異が他のゲノム変異に比べて有意に多くのタンパク質間相互作用を阻害することも知られている。したがって、インタラクトーム情報を個人レベルで調べることが可能になればパーソナルゲノム情報に加えてより高度な細胞あるいは疾病の動態予測が可能になる。またより高速なインタラクトーム測定技術の開発は様々な生物種のゲノム情報がどのように形質として転写されるのか知る大きな手がかりともなり、本技術が医療分野および基礎生物学分野に与える影響は大きい。

Research Products

• [Int'l Joint Research] University of Toronto/Laval University/Mt Sinai Hospital(カナダ)
• [Int'l Joint Research] Laval University/University of Toronto/Mt Sinai Hospital(カナダ)
• [Int'l Joint Research] Laval University/University of Toronto/Mt Sinai Hospital(カナダ)
• [Journal Article] Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways (2020)
  • Author(s): Kim Jae-Hong、Seo Yeojin、Jo Myungjin、Jeon Hyejin、Kim Young-Seop、Kim Eun-Jung、Seo Donggun、Lee Won-Ha、Kim Sang Ryong、Yachie Nozomu、Zhong Quan、Vidal Marc、Roth Frederick P.、Suk Kyoungho
  • Journal Title: Journal of Biological Chemistry Volume: 295 Issue: 50 Pages: 16906-16919
  • DOI: 10.1074/jbc.ra120.014831
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Highly Combinatorial Genetic Interaction Analysis Reveals a Multi-Drug Transporter Influence Network (2020)
  • Author(s): Celaj Albi、Gebbia Marinella、Musa Louai、Cote Atina G.、Snider Jamie、Wong Victoria、Ko Minjeong、Fong Tiffany、Bansal Paul、Mellor Joseph C.、Seesankar Gireesh、Nguyen Maria、Zhou Shijie、Wang Liangxi、Kishore Nishka、Stagljar Igor、Suzuki Yo、Yachie Nozomu、Roth Frederick P.
  • Journal Title: Cell Systems Volume: 10 Issue: 1 Pages: 25-38.e10
  • DOI: 10.1016/j.cels.2019.09.009
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Complete Genome Sequence of Bacillus sp. Strain KH172YL63, Isolated from Deep-Sea Sediment (2020)
  • Author(s): Murai Yumi、Masuda Takahiro、Onuma Yasuhide、Evans-Yamamoto Daniel、Takeuchi Nao、Mori Hideto、Masuyama Nanami、Ishiguro Soh、Yachie Nozomu、Arakawa Kazuharu
  • Journal Title: Microbiology Resource Announcements Volume: 9 Issue: 16
  • DOI: 10.1128/mra.00291-20
  • Peer Reviewed
• [Journal Article] Use of Freeze-thawed Embryos for High-efficiency Production of Genetically Modified Mice (2020)
  • Author(s): Nishizono Hirofumi、Darwish Mohamed、Uosaki Hideki、Masuyama Nanami、Seki Motoaki、Abe Hiroyuki、Yachie Nozomu、Yasuda Ryohei
  • Journal Title: Journal of Visualized Experiments Volume: － Issue: 158 Pages: 1-1
  • DOI: 10.3791/60808
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Perturbing proteomes at single residue resolution using base editing (2020)
  • Author(s): Despres Philippe C.、Dube Alexandre K.、Seki Motoaki、Yachie Nozomu、Landry Christian R.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 1871-1871
  • DOI: 10.1038/s41467-020-15796-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Yeast-Based Genetic Interaction Analysis of Human Kinome (2020)
  • Author(s): Kim Jae-Hong、Seo Yeojin、Jo Myungjin、Jeon Hyejin、Lee Won-Ha、Yachie Nozomu、Zhong Quan、Vidal Marc、Roth Frederick P.、Suk Kyoungho
  • Journal Title: Cells Volume: 9 Issue: 5 Pages: 1156-1156
  • DOI: 10.3390/cells9051156
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Base editors for simultaneous introduction of C-to-T and A-to-G mutations (2020)
  • Author(s): Sakata Rina C.、Ishiguro Soh、Mori Hideto、Tanaka Mamoru、Tatsuno Kenji、Ueda Hiroki、Yamamoto Shogo、Seki Motoaki、Masuyama Nanami、Nishida Keiji、Nishimasu Hiroshi、Arakawa Kazuharu、Kondo Akihiko、Nureki Osamu、Tomita Masaru、Aburatani Hiroyuki、Yachie Nozomu
  • Journal Title: Nature Biotechnology Volume: na Issue: 7 Pages: 865-869
  • DOI: 10.1038/s41587-020-0509-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] DNA event recorders send past information of cells to the time of observation (2019)
  • Author(s): Ishiguro Soh、Mori Hideto、Yachie Nozomu
  • Journal Title: Current Opinion in Chemical Biology Volume: 52 Pages: 54-62
  • DOI: 10.1016/j.cbpa.2019.05.009
  • Peer Reviewed
• [Journal Article] DNA barcodes evolve for high-resolution cell lineage tracing (2019)
  • Author(s): Masuyama Nanami、Mori Hideto、Yachie Nozomu
  • Journal Title: Current Opinion in Chemical Biology Volume: 52 Pages: 63-71
  • DOI: 10.1016/j.cbpa.2019.05.014
  • Peer Reviewed
• [Journal Article] The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs (2019)
  • Author(s): Marchant Axelle、Cisneros Angel F、Dube Alexandre K、Gagnon-Arsenault Isabelle、Ascencio Diana、Jain Honey、Aube Simon、Eberlein Chris、Evans-Yamamoto Daniel、Yachie Nozomu、Landry Christian R
  • Journal Title: eLife Volume: 8
  • DOI: 10.7554/elife.46754
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A genome-scale CRISPR/Cas9 knockout screening reveals SH3D21 as a sensitizer for gemcitabine (2019)
  • Author(s): Masoudi Mohammad、Seki Motoaki、Yazdanparast Razieh、Yachie Nozomu、Aburatani Hiroyuki
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 19188-19188
  • DOI: 10.1038/s41598-019-55893-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The role of structural pleiotropy and regulatory evolution in the retention of heteromers of paralogs (2019)
  • Author(s): Marchant Axelle、Cisneros Angel F.、Dube Alexandre K、Gagnon-Arsenault Isabelle、Ascencio Diana、Jain Honey A.、Aube Simon、Eberlein Chris、Evans-Yamamoto Daniel、Yachie Nozomu、Landry Christian R
  • Journal Title: bioRxiv Volume: NA
  • DOI: 10.1101/564401
  • Int'l Joint Research
• [Journal Article] Complete Genome Sequence of Psychrobacter sp. Strain KH172YL61, Isolated from Deep-Sea Sediments in the Nankai Trough, Japan (2019)
  • Author(s): Evans-Yamamoto Daniel、Takeuchi Nao、Masuda Takahiro、Murai Yumi、Onuma Yasuhide、Mori Hideto、Masuyama Nanami、Ishiguro Soh、Yachie Nozomu、Arakawa Kazuharu
  • Journal Title: Microbiology Resource Announcements Volume: 8 Issue: 16
  • DOI: 10.1128/mra.00326-19
  • Peer Reviewed
• [Journal Article] beditor: A Computational Workflow for Designing Libraries of Guide RNAs for CRISPR-Mediated Base Editing (2019)
  • Author(s): Dandage Rohan、Despres Philippe C.、Yachie Nozomu、Landry Christian R.
  • Journal Title: Genetics Volume: NA Issue: 2 Pages: 377-385
  • DOI: 10.1534/genetics.119.302089
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fast and global detection of periodic sequence repeats in large genomic resources (2018)
  • Author(s): Mori Hideto、Evans-Yamamoto Daniel、Ishiguro Soh、Tomita Masaru、Yachie Nozomu
  • Journal Title: Nucleic Acids Research Volume: 47 Issue: 2 Pages: e8-e8
  • DOI: 10.1093/nar/gky890
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Engineered CRISPR-Cas9 nuclease with expanded targeting space (2018)
  • Author(s): Nishimasu Hiroshi、Shi Xi、Ishiguro Soh、Gao Linyi、Hirano Seiichi、Okazaki Sae、Noda Taichi、Abudayyeh Omar O.、Gootenberg Jonathan S.、Mori Hideto、Oura Seiya、Holmes Benjamin、Tanaka Mamoru、Seki Motoaki、Hirano Hisato、Aburatani Hiroyuki、Ishitani Ryuichiro、Ikawa Masahito、Yachie Nozomu、Zhang Feng、Nureki Osamu
  • Journal Title: Science Volume: 361 Issue: 6408 Pages: 1259-1262
  • DOI: 10.1126/science.aas9129
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Double Selection Enhances the Efficiency of Target-AID and Cas9-Based Genome Editing in Yeast (2018)
  • Author(s): Despres Philippe C、Dube Alexandre K、Nielly-Thibault Lou、Yachie Nozomu、Landry Christian R
  • Journal Title: G3: Genes|Genomes|Genetics Volume: 8 Issue: 10 Pages: 3163-3171
  • DOI: 10.1534/g3.118.200461
  • Peer Reviewed / Int'l Joint Research
• [Presentation] DNA Event Recording Biology (2020)
  • Author(s): Yachie N
  • Organizer: CRISPR and Beyond: Perturbations at Scale to Understand Genomes
  • Int'l Joint Research / Invited
• [Presentation] Towards a high-resolution whole-body map of cell lineage and differentiation trajectories in mammalian development (2020)
  • Author(s): Yachie N
  • Organizer: Cascadia 2.0
  • Int'l Joint Research / Invited
• [Presentation] DNA barcode technologies to dissect heterogeneous biological systems (2019)
  • Author(s): Yachie N
  • Organizer: The 13th Intn’l Workshop on Advanced Genomics
  • Int'l Joint Research / Invited
• [Presentation] Recording cellular events in DNA (2019)
  • Author(s): Yachie N
  • Organizer: Asian Synthetic Biology Association
  • Int'l Joint Research / Invited
• [Presentation] Recording cellular events in DNA (2019)
  • Author(s): Yachie N
  • Organizer: Frontiers in Genome Engineering
  • Int'l Joint Research / Invited
• [Presentation] Bringing the sense of amazing yeast genetics to mammalian biology (2018)
  • Author(s): 谷内江 望
  • Organizer: 第22回酵母合同シンポジウム
  • Invited
• [Presentation] Synthetic DNA memory devices to measure molecular and cellular dynamics (2018)
  • Author(s): 谷内江 望
  • Organizer: 生命科学系フロンティアミーティング 2018
  • Invited
• [Presentation] Developing new genome editing technologies (2018)
  • Author(s): 谷内江 望
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] A new genetic marker to analyze molecular dynamics of a same clone in complex cell populations (2018)
  • Author(s): Nozomu Yachie
  • Organizer: The 91st Annual Meeting of the Japanese Biochemical Society
• [Presentation] Scaling up massively parallel experiments using DNA barcodes (2018)
  • Author(s): Nozomu Yachie
  • Organizer: JST ImPACT Artificial Cell Program, Tokyo
  • Int'l Joint Research / Invited
• [Presentation] Chasing molecular and cellular dynamics using DNA barcodes (2018)
  • Author(s): Nozomu Yachie
  • Organizer: Cell Mapping Symposium, San Diego, US
  • Int'l Joint Research / Invited
• [Presentation] We do not have a time machine, but can install a recording system to a cell (2018)
  • Author(s): Nozomu Yachie
  • Organizer: Asian Synthetic Biology Association 2018, Ceju, Korea
  • Int'l Joint Research / Invited
• [Remarks] Yachie Laboratory at the University of Tokyo
  • URL: http://yachie-lab.org/
• [Patent(Industrial Property Rights)] 2種の核酸塩基変換酵素が融合されたCasタンパク質を利用したゲノム編集システム (2019)
  • Inventor(s): 谷内江望、石黒宗、坂田莉奈、森秀人
  • Industrial Property Rights Holder: 谷内江望、石黒宗、坂田莉奈、森秀人
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019
• [Patent(Industrial Property Rights)] 汎用的繰り返しDNAアセンブリ技術（FRACTALアセンブリ） (2019)
  • Inventor(s): 谷内江望、山口七海、森秀人
  • Industrial Property Rights Holder: 谷内江望、山口七海、森秀人
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2020-053077
  • Filing Date: 2019