Support for International Cooperation in Systems Cancer in Neo-dimension

2021 Fiscal Year Annual Research Report

• Project Area: Conquering cancer through neo-dimensional systems understanding
• Project/Area Number: 15K21741
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 宮野 悟 東京医科歯科大学, M&Dデータ科学センター, 特任教授 (50128104)
• Project Period (FY): 2015-11-06 – 2022-03-31
• Keywords: がん / システム生物学 / ゲノム科学 / バイオインフォマティクス / 人工知能

Outline of Annual Research Achievements

COVID-19が2021年度も治まることなく、研究者の派遣や受け入れについては極めて限定的にならざるを得なかった。しかし、ZoomやWebExなのどの活用が全世界的に普及し、コミュニケーションは加速したといってもよい。特に、スウェーデンカロリンスカ研究所の客員教授の小川誠司の連携は優れた実績を生み、拠点形成に大きく貢献したと考えている。また、スウェーデン、ドイツ、米国とも共著の研究成果を発表できている。連携のベースは、がんに関するデータの解析であり、これまでと同様、東京大学医科学研究所ヒトゲノム解析センターのスーパーコンピュータSHIROKANEをフルに活用する支援を実施することでCOVID-19の影響を受けることなく研究を発展させた。その成果は一連の国際共同研究論文や、国際学会でのリーダーシップ的講演（オンライン）として結実している。人的交流がほぼ不可能であったなかで、本国際共同研究支援班のこれまでの活動から、ドイツ・フンボルト大学Edda Klipp教授などが、来日し、経費はこれまでの研究で産生されたデータ及び2021年度に新たに産生されたデータを高速ディスクアレイに保管して解析することに用いることで、国際連携と拠点形成のミッションを果たすことができた。この連携活動は、班員の岡田随象、小川誠司、宮野悟等によりCOVID-19 Host Genetics Initiativeという国際連携への参加を実現した(Nature 2021)。「システム癌新次元」は、がん研究に限るという方針ではなく、新たな方法論を生命科学に導入・展開し有効性をみることも目的の一つであり、結果、大きな波及効果があった。

Research Products

• [Int'l Joint Research] カロリンスカ研究所(スウェーデン)
  • Country Name: SWEDEN
  • Counterpart Institution: カロリンスカ研究所
• [Int'l Joint Research] Sanger Institute(英国)
  • Country Name: UNITED KINGDOM
  • Counterpart Institution: Sanger Institute
• [Int'l Joint Research] Ichahn School of Medicine at Mount Sinai/Harvard Medical School(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Ichahn School of Medicine at Mount Sinai/Harvard Medical School
• [Int'l Joint Research] フンボルト大学(ドイツ)
  • Country Name: GERMANY
  • Counterpart Institution: フンボルト大学
• [Int'l Joint Research] Seoul National University(韓国)
  • Country Name: KOREA (REP. OF KOREA)
  • Counterpart Institution: Seoul National University
• [Journal Article] The landscape of genetic aberrations in myxofibrosarcoma (2022)
  • Author(s): Takeuchi Y, Yoshida K, Halik A, Kunitz A, Suzuki H, Kakiuchi N, Shiozawa Y, Yokoyama A, Inoue Y, Hirano T, Yoshizato T, Aoki K, Fujii Y, Nannya Y, Makishima H, Pfitzner BM, Bullinger L, Hirata M, Jinnouchi K, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Okamoto T, Haga H, Ogawa S, Damm F.
  • Journal Title: Int J Cancer Volume: - Pages: -
  • DOI: 10.1002/ijc.34051
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach (2022)
  • Author(s): Li X, Shong K, Kim W, Yuan M, Yang H, Sato Y, Kume H, Ogawa S, Turkez H, Shoaie S, Boren J, Nielsen J, Uhlen M, Zhang C, Mardinoglu A
  • Journal Title: EBioMedicine Volume: - Pages: -
  • DOI: 10.1016/j.ebiom.2022.103963
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pseudouridine-modified tRNA fragments repress aberrant protein synthesis and predict leukaemic progression in myelodysplastic syndrome (2022)
  • Author(s): Guzzi N, Muthukumar S, Todisco G, Ngoc PCT, Madej M, Munita R, Fazio S, Ekström S, Mortera-Blanco T, Jansson M, Nannya Y, Cazzola M, Ogawa S, Malcovati L, Hellström-Lindberg E, Dimitriou M, Bellodi C
  • Journal Title: Nat Cell Biol Volume: 24(3) Pages: 299-306
  • DOI: 10.1038/s41556-022-00852-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Aged healthy mice acquire clonal hematopoiesis mutations (2022)
  • Author(s): Chin DWL, Yoshizato T, Virding Culleton S, Grasso F, Barbachowska M, Ogawa S, Jacobsen SEW, Woll PS
  • Journal Title: Blood Volume: 139(4) Pages: 629-634
  • DOI: 10.1182/blood.2021014235
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mapping the human genetic architecture of COVID-19 (2022)
  • Author(s): COVID-19 Host Genetics Initiative
  • Journal Title: Nature Volume: 600(7889) Pages: 472-477
  • DOI: 10.1038/s41586-021-03767-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Patient-specific MDS-RS iPSCs define the mis-spliced transcript repertoire and chromatin landscape of SF3B1-mutant HSPCs (2022)
  • Author(s): Asimomitis G, Deslauriers AG, Kotini AG, Bernard E, Esposito D, Olszewska M, Spyrou N, Arango Ossa J, Mortera-Blanco T, Koche R, Nannya Y, Malcovati L, Ogawa S, Cazzola M, Aaronson SA, Hellström-Lindberg E, Papaemmanuil E, Papapetrou EP
  • Journal Title: Blood Adv Volume: 6(10) Pages: 2992-3005
  • DOI: 10.1182/bloodadvances
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Co-mutation pattern, clonal hierarchy, and clone size concur to determine disease phenotype of SRSF2P95-mutated neoplasms (2021)
  • Author(s): Todisco G, Creignou M, Guglielmelli P, Rumi E, Roncador M, Rizzo E, Nannya Y, Pietra D, Elena C, Bono E, Molteni E, Rosti V, Catricalá S, Sarchi M, Dimitriou M, Ungerstedt J, Vannucchi AM, Hellström-Lindberg E, Ogawa S, Cazzola M, Malcovati L
  • Journal Title: Leukemia Volume: 35(8) Pages: 2371-2381
  • DOI: 10.1038/s41375-020-01106-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular classification and diagnostics of upper urinary tract urothelial carcinoma (2021)
  • Author(s): Fujii Y, Sato Y, Suzuki H, Kakiuchi N, Yoshizato T, Lenis AT, Maekawa S, Yokoyama A, Takeuchi Y, Inoue Y, Ochi Y, Shiozawa Y, Aoki K, Yoshida K, Kataoka K, Nakagawa MM, Nannya Y, Makishima H, Miyakawa J, Kawai T, Morikawa Miyano S, Coleman JA, Homma Y, Solit DB, Kume H, Ogawa S
  • Journal Title: Cancer Cell Volume: 39(6) Pages: 793-809
  • DOI: 10.1016/j.ccell.2021.05.008
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Stratification of patients with clear cell renal cell carcinoma to facilitate drug repositioning (2021)
  • Author(s): Li X, Kim W, Juszczak K, Arif M, Sato Y, Kume H, Ogawa S, Turkez H, Boren J, Nielsen J, Uhlen M, Zhang C, Mardinoglu A
  • Journal Title: iScience Volume: 24(7) Pages: 102722
  • DOI: 10.1016/j.isci.2021.102722
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia (2021)
  • Author(s): Ochi Y, Yoshida K, Huang YJ, Kuo MC, Nannya Y, Sasaki K, Mitani K, Hosoya N, Hiramoto N, Ishikawa T, Branford S, Shanmuganathan N, Bera R, Shiozawa Y, Zhao L, Takeda J, Watatani Y, Okuda R, Makishima H, Shiraishi Y, Sanada M, Takaori-Kondo A, Miyano S, Ogawa S, Shih LY
  • Journal Title: Nat Commun Volume: 12(1) Pages: 2833
  • DOI: 10.1038/s41467-021-23097-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes (2021)
  • Author(s): Bernard E, Nannya Y, Hasserjian RP, Devlin SM, Follo MY, Thol F, Pinheiro RF, Schanz J, T, Polprasert C, Bennett JM, Klimek VM, Savona MR, Belickova M, Ganster C, Palomo L, Sanz G, Ades L, Della Porta MG, Elias HK, Smith AG, Werner Y, Patel M, Viale A, Vanness K, Neuberg DS, Stevenson KE, Ogawa S, Papaemmanuil E
  • Journal Title: Nat Med Volume: 27(5) Pages: 927
  • DOI: 10.1038/s41591-021-01367-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia (2021)
  • Author(s): Lundgren S, Kankainen M, Huuhtanen J, Walldin G, Kerr CM, Clemente M, Ebeling F, Rajala H, Brück O, Lähdesmäki H, Hannula S, Hannunen T, Ellonen P, Young NS, Ogawa S, Maciejewski JP, Hellström-Lindberg E, Mustjoki S
  • Journal Title: Leukemia Volume: 35(5) Pages: 1365-1379
  • DOI: 10.1038/s41375-021-01231-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial (2021)
  • Author(s): Hoyer K, Hablesreiter R, Inoue Y, Yoshida K, Briest F, Christen F, Kakiuchi N, Yoshizato T, Shiozawa Y, Shiraishi Y, Striefler JK, Bischoff S, Lohneis P, Putter H, Blau O, Keilholz U, Bullinger L, Pelzer U, Hummel M, Riess H, Ogawa S, Sinn M, Damm F
  • Journal Title: EBioMedicine Volume: 66 Pages: 103327
  • DOI: 10.1016/j.ebiom.2021.103327
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonal expansion in non-cancer tissues (2021)
  • Author(s): 14.Kakiuchi N, Ogawa S
  • Journal Title: Nat Rev Cancer Volume: 21(4) Pages: 239-256
  • DOI: 10.1038/s41568-021-00335-3
  • Peer Reviewed / Open Access
• [Presentation] Cancer mutations in normal tissues (2021)
  • Author(s): Seishi Ogawa
  • Organizer: The 1st International Symposium of CCII-Bioinformatics and its application to cancer and other diseases
  • Int'l Joint Research
• [Presentation] Clonal Expansion in Apparently Normal Tissues (2021)
  • Author(s): Seishi Ogawa
  • Organizer: JCA-AACR Precision Cancer Medicine International Conference
  • Int'l Joint Research
• [Presentation] Inflammation (2021)
  • Author(s): Seishi Ogawa
  • Organizer: AACR-JCA Joint Session explores tumor evolution
  • Int'l Joint Research
• [Presentation] Important Issues for Realizing AI Hospital : from cancer genomic medicine (2021)
  • Author(s): Satoru Miyano
  • Organizer: German Centre for Research Innovation Workshop (Online)
  • Int'l Joint Research / Invited
• [Presentation] Network Approaches to Drug Target/Resistance with Supercomputers (2021)
  • Author(s): Satoru Miyano
  • Organizer: 第80回日本癌学会学術総会Symposia 20: Drug discovery and diagnosis enhanced with AI
  • Int'l Joint Research / Invited
• [Presentation] Challenges to Personalized Medicine by AI and Big Data - Genomes to Networks (2021)
  • Author(s): Satoru Miyano
  • Organizer: 第62回日本神経学会学術大会Neuroscience Frontier Symposium 02 “Frontiers of neuroscience and medicine accelerated by big data and AI”
  • Int'l Joint Research / Invited
• [Presentation] がんゲノム医療と人工知能 (2021)
  • Author(s): 宮野 悟
  • Organizer: 第59回日本癌治療学会学術集会会長企画シンポジウム「AI oncology の現状と今後の展望」
  • Invited
• [Presentation] 医療の未来を拓くために必要なAI技術 (2021)
  • Author(s): 宮野 悟
  • Organizer: 第158回日本医学会シンポジウム
  • Invited
• [Presentation] メディカルデータサイエンスの現状 (2021)
  • Author(s): 宮野 悟
  • Organizer: 第110回日本病理学会総会. 特別企画
  • Invited
• [Presentation] 人工知能と大規模データ解析で変わるがんゲノム研究と医療 (2021)
  • Author(s): 宮野 悟
  • Organizer: 第３９回日本脳腫瘍学会
  • Invited
• [Presentation] スーパーコンピュータを用いた医療とテクノロジーの統合 (2021)
  • Author(s): 宮野 悟
  • Organizer: 第6回医療と創造性及び世界平和シンポジウム
  • Invited
• [Remarks] システム癌新次元ホームページ
  • URL: http://neosystemscancer.hgc.jp/home