Development of Bayesian modeling approach to understand multicellular dynamics

• Project/Area Number: 20H04281
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Nagoya University
• Principal Investigator: Shimamura Teppei 名古屋大学, 医学系研究科, 教授 (00623943)
• Co-Investigator(Kenkyū-buntansha): 阿部 興 神戸薬科大学, 薬学部, 講師 (70832533)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2022: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2020: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: ベイズモデル / 一細胞解析 / 細胞間コミュニケーション / 細胞運命決定 / 深層生成モデル / マルチオミクス / 因子分解 / 細胞ダイナミクス / シングルセルオミクス / 空間トランスクリプトーム / ベイズモデリング / 時空間解析 / 相互作用ネットワーク / 行列因子分解

Outline of Research at the Start

本研究では、最先端のベイズモデリングを基軸として、一細胞レベルでの多次元データを処理・解析・統合し、多細胞が生み出す複雑な相互作用ネットワークのダイナミクスを理解するための情報解析技術を開発する。本研究の進展により、生命の複雑さにまつわる法則性を発見し、生命を理解するのみならず、創薬の効率化、新薬の開発、薬剤の有効性や副作用の高精度予測等などの関連分野への波及効果も期待できる。

Outline of Final Research Achievements

In this research project, we target the cancer-immune complex system and develop a cutting-edge single-cell analysis platform, leveraging advanced mathematical modeling and artificial intelligence (AI), to elucidate the mechanisms by which tumor diversity induces treatment resistance at the single-cell level. Specifically, we (1) developed Bayesian modeling techniques to estimate causal effects between cellular populations, (2) created statistical modeling techniques to describe the dynamics of the complex system leading to treatment resistance, and (3) advanced deep learning techniques for exploring molecular regulatory mechanisms within cellular populations.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、革新的な一細胞オミクス計測技術によるデータ取得、最先端の数理モデリング・人工知能技術の開発、ヒト臨床検体およびモデル動物によるモデルの概念実証に関する一連の研究を、確固たる研究連携基盤の上で実施した。本研究で開発した解析手法により、がんの複雑系の解明、さらにはがんの診断、治療、治療効果予測などの臨床応用に向けた強力な研究開発基盤が構築されることが期待される。

Research Products

• [Journal Article] Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma (2023)
  • Author(s): Kitagawa A, Osawa T,Noda M,Kobayashi Y, Aki S,Nakano Y,Saito T,Shimizu D,Komatsu H,Sugaya M,Takahashi J,...Mimori K.
  • Journal Title: Br J Cancer Volume: - Issue: 12 Pages: 2206-2217
  • DOI: 10.1038/s41416-023-02256-4
  • Peer Reviewed / Open Access
• [Journal Article] Increased flexibility of the SARS-CoV-2 RNA-binding site causes resistance to remdesivir (2023)
  • Author(s): Torii Shiho、Kim Kwang Su、Koseki Jun、Suzuki Rigel、Iwanami Shoya、Fujita Yasuhisa、Jeong Yong Dam、Ito Jumpei、Asakura Hiroyuki、Nagashima Mami、Sadamasu Kenji、Yoshimura Kazuhisa、Sato Kei、Matsuura Yoshiharu、Shimamura Teppei、Iwami Shingo、Fukuhara Takasuke、The Genotype to Phenotype Japan (G2P-Japan) Consortium
  • Journal Title: PLOS Pathogens Volume: 19 Issue: 3 Pages: e1011231-e1011231
  • DOI: 10.1371/journal.ppat.1011231
  • Peer Reviewed / Open Access
• [Journal Article] Spatial and single-cell transcriptomics decipher the cellular environment containing HLA-G+ cancer cells and SPP1+ macrophages in colorectal cancer. (2023)
  • Author(s): Ozato Y, Kojima Y, Kobayashi Y, Hisamatsu Y, Toshima T, Yonemura Y, Masuda T, Kagawa K, Goto Y, Utou M, Fukunaga M,... Mimori K.
  • Journal Title: Cell Rep Volume: 42(1) Issue: 1 Pages: 111929-111929
  • DOI: 10.1016/j.celrep.2022.111929
  • Peer Reviewed / Open Access
• [Journal Article] Bayesian statistical method for detecting structural and topological diversity in polymorphic proteins (2022)
  • Author(s): Hayashi Shuto、Koseki Jun、Shimamura Teppei
  • Journal Title: Computational and Structural Biotechnology Journal Volume: 20 Pages: 6519-6525
  • DOI: 10.1016/j.csbj.2022.11.038
  • Peer Reviewed / Open Access
• [Journal Article] Smoking enhances the expression of angiotensin‐converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection (2022)
  • Author(s): Suzuki Rigel、Ono Yuki、Noshita Koji、Kim Kwang Su、Ito Hayato、Morioka Yuhei、Tamura Tomokazu、Okuzaki Daisuke、Tagawa Tetsuzo、Takenaka Tomoyoshi、Yoshizumi Tomoharu、Shimamura Teppei、Iwami Shingo、Fukuhara Takasuke
  • Journal Title: Microbiology and Immunology Volume: 67 Issue: 1 Pages: 22-31
  • DOI: 10.1111/1348-0421.13034
  • Peer Reviewed
• [Journal Article] Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization (2022)
  • Author(s): Ikeda Kei、Nakada Taka-Aki、Kageyama Takahiro、Tanaka Shigeru、Yoshida Naoki、Ishikawa Tetsuo、Goshima Yuki、Otaki Natsuko、Iwami Shingo、Shimamura Teppei、Taniguchi Toshibumi、Igari Hidetoshi、Hanaoka Hideki、Yokote Koutaro、Tsuyuzaki Koki、Nakajima Hiroshi、Kawakami Eiryo
  • Journal Title: iScience Volume: 25 Issue: 10 Pages: 105237-105237
  • DOI: 10.1016/j.isci.2022.105237
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic remodeling of pyrimidine synthesis pathway and serine synthesis pathway in human glioblastoma (2022)
  • Author(s): Nakamizo Akira、Miyamatsu Yuichiro、Hirose Haruka、Amano Toshiyuki、Matsuo Satoshi、Fujiwara Minako、Shimamura Teppei、Yoshimoto Koji
  • Journal Title: Scientific Reports Volume: 12 Issue: 1 Pages: 16277-16277
  • DOI: 10.1038/s41598-022-20613-w
  • Peer Reviewed / Open Access
• [Journal Article] Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis. (2022)
  • Author(s): Murakami, A., Noda, S., Kazuta, T., Hirano, S., Kimura, S., Nakanishi, H., Matsuo, K., Tsujikawa, K., Iida, M., Koike, H., Sakamoto, K., Hara, Y., Kuru, S., Kadomatsu, K., Shimamura, T., Ogi, T., Katsuno, M.
  • Journal Title: Ann Clin Transl Neurol. Volume: 9 Issue: 10 Pages: 1602-1615
  • DOI: 10.1002/acn3.51657
  • Peer Reviewed / Open Access
• [Journal Article] An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis (2022)
  • Author(s): Takahashi K, Abe K, Kubota SI, Fukatsu N, Morishita Y, Yoshimatsu Y, Satoshi Hirakawa, Yoshiaki Kubota, Tetsuro Watabe, Shogo Ehata, Hiroki R. Ueda, Teppei Shimamura, Kohei Miyazono
  • Journal Title: Nature Communiactions Volume: 13 Issue: 1 Pages: 5239-5239
  • DOI: 10.1038/s41467-022-32848-2
  • Peer Reviewed / Open Access
• [Journal Article] A bifurcation concept for B-lymphoid/plasmacytoid dendritic cells with largely fluctuating transcriptome dynamics. (2022)
  • Author(s): Nagaharu K, Kojima Y, Hirose H, Minoura K, Hinohara K, Minami H, Kageyama Y, Sugimoto Y, Masuya M, Nii S, Seki M, Suzuki Y, Tawara I, Shimamura T, Katayama N, Nishikawa H, Ohishi K.
  • Journal Title: Cell Rep. Volume: 40 Issue: 9 Pages: 111260-111260
  • DOI: 10.1016/j.celrep.2022.111260
  • Peer Reviewed / Open Access
• [Journal Article] UVB-Induced Skin Autoinflammation Due to Nlrp1b Mutation and Its Inhibition by Anti-IL-1β Antibody (2022)
  • Author(s): Murase Yuya、Takeichi Takuya、Koseki Jun、Miyasaka Yuki、Muro Yoshinao、Ohno Tamio、Shimamura Teppei、Akiyama Masashi
  • Journal Title: Frontiers in Immunology Volume: 13 Pages: 876390-876390
  • DOI: 10.3389/fimmu.2022.876390
  • Peer Reviewed / Open Access
• [Journal Article] Exome sequencing of Japanese schizophrenia multiplex families supports the involvement of calcium ion channels (2022)
  • Author(s): Toyama Miho、Takasaki Yuto、Branko Aleksic、Kimura Hiroki、Kato Hidekazu、Nawa Yoshihiro、Kushima Itaru、Ishizuka Kanako、Shimamura Teppei、Ogi Tomoo、Ozaki Norio
  • Journal Title: PLOS ONE Volume: 17(5) Issue: 5 Pages: e0268321-e0268321
  • DOI: 10.1371/journal.pone.0268321
  • Peer Reviewed / Open Access
• [Journal Article] A mixture-of-experts deep generative model for integrated analysis of single-cell multiomics data (2021)
  • Author(s): Minoura Kodai、Abe Ko、Nam Hyunha、Nishikawa Hiroyoshi、Shimamura Teppei
  • Journal Title: Cell Reports Methods Volume: 1(5) Issue: 5 Pages: 100071-100071
  • DOI: 10.1016/j.crmeth.2021.100071
• [Journal Article] Depletion of central memory CD8+ T cells might impede the antitumor therapeutic effect of Mogamulizumab (2021)
  • Author(s): Maeda Yuka、Wada Hisashi、Sugiyama Daisuke、Saito Takuro、Irie Takuma、Itahashi Kota、Minoura Kodai、Suzuki Susumu、Kojima Takashi、Kakimi Kazuhiro、Nakajima Jun、Funakoshi Takeru、Iida Shinsuke、Oka Mikio、Shimamura Teppei、Doi Toshihiko、Doki Yuichiro、Nakayama Eiichi、Ueda Ryuzo、Nishikawa Hiroyoshi
  • Journal Title: Nature Communications Volume: 12(1) Issue: 1 Pages: 7280-7280
  • DOI: 10.1038/s41467-021-27574-0
  • Peer Reviewed / Open Access
• [Journal Article] Hierarchical non-negative matrix factorization using clinical information for microbial communities (2021)
  • Author(s): Abe Ko、Hirayama Masaaki、Ohno Kinji、Shimamura Teppei
  • Journal Title: BMC Genomics Volume: 22 Issue: 1 Pages: 104-104
  • DOI: 10.1186/s12864-021-07401-y
  • Peer Reviewed / Open Access
• [Journal Article] CYBERTRACK2.0: zero-inflated model-based cell clustering and population tracking method for longitudinal mass cytometry data (2020)
  • Author(s): Minoura K*, Abe K*, Maeda Y, Nishikawa H, Shimamura T§
  • Journal Title: Bioinformatics Volume: - Issue: 11 Pages: 873-873
  • DOI: 10.1093/bioinformatics/btaa873
  • Peer Reviewed / Open Access
• [Journal Article] Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson’s Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder (2020)
  • Author(s): Nishiwaki Hiroshi、Hamaguchi Tomonari、Ito Mikako、Ishida Tomohiro、Maeda Tetsuya、Kashihara Kenichi、Tsuboi Yoshio、Ueyama Jun、Shimamura Teppei、Mori Hiroshi、Kurokawa Ken、Katsuno Masahisa、Hirayama Masaaki、Ohno Kinji
  • Journal Title: mSystems Volume: 5 Issue: 6
  • DOI: 10.1128/msystems.00797-20
  • Peer Reviewed / Open Access
• [Journal Article] Model-based clustering for flow and mass cytometry data with clinical information (2020)
  • Author(s): Abe K, Minoura K, Maeda Y, Nishikawa H, Shimamura T§
  • Journal Title: BMC Bioinformatics Volume: 21(Suppl 13) Issue: S13 Pages: 393-393
  • DOI: 10.1186/s12859-020-03671-7
  • Peer Reviewed / Open Access
• [Journal Article] ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk (2020)
  • Author(s): Mariko Sekiguchi, Akiko Kodama,... Emiko Shishido,... Daisuke Mori, Norio Ozaki
  • Journal Title: Translational psychiatry Volume: 10 Issue: 1 Pages: 1-15
  • DOI: 10.1038/s41398-020-00917-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets. (2020)
  • Author(s): Sekiguchi M, Seki M, Kawai T, Yoshida K, Yoshida M, Isobe T, Hoshino N, Shirai R, Tanaka M, Souzaki R, Watanabe K, Arakawa Y, Nannya Y, Suzuki H, Fujii Y, Kataoka K, Shiraishi Y, Chiba K, Tanaka H, Shimamura T, Sato Y, Sato-Otsubo A, Kimura S, Kubota Y, Hiwatari M, et al
  • Journal Title: NPJ Precis Oncol. Volume: Jul 7;4:20. Issue: 1 Pages: 20-20
  • DOI: 10.1038/s41698-020-0125-y
  • Peer Reviewed / Open Access
• [Journal Article] Meta‐Analysis of Gut Dysbiosis in Parkinson's Disease (2020)
  • Author(s): Nishiwaki Hiroshi、Ito Mikako、Ishida Tomohiro、Hamaguchi Tomonari、Maeda Tetsuya、Kashihara Kenichi、Tsuboi Yoshio、Ueyama Jun、Shimamura Teppei、Mori Hiroshi、Kurokawa Ken、Katsuno Masahisa、Hirayama Masaaki、Ohno Kinji
  • Journal Title: Movement Disorders Volume: 35 Issue: 9 Pages: 1626-1635
  • DOI: 10.1002/mds.28119
  • Peer Reviewed / Open Access
• [Journal Article] EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells. (2020)
  • Author(s): Yoshino S, Matsui Y, Fukui Y, Seki M, Yamaguchi K, Kanamori A, Saitoh Y, Shimamura T, Suzuki Y, Furukawa Y, Kaneko S, Seiki M, Murakami Y, Inoue JI, Sakamoto T.
  • Journal Title: Sci Rep Volume: 10 Issue: 1 Pages: 9275-9275
  • DOI: 10.1038/s41598-020-66455-2
  • Peer Reviewed / Open Access
• [Journal Article] Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells (2020)
  • Author(s): Higashijima Y, Matsui Y, Shimamura T, Nakaki R, Nagai N, Tsutsumi S, Abe Y, Link VM, Osaka M, Yoshida M, Watanabe R, Tanaka T, Taguchi A, Miura M, Ruan X, Li G, Inoue T, Nangaku M, Kimura H, Furukawa T, Aburatani H, Wada Y, Ruan Y, Glass CK, Kanki Y
  • Journal Title: The EMBO Journal Volume: 39 Issue: 7 Pages: 1-1
  • DOI: 10.15252/embj.2019103949
  • NAID: 120006902140
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 深層生成モデルで読み解く生命システムの動作原理 (2022)
  • Author(s): 島村 徹平
  • Organizer: 第7回理論免疫学ワークショップ
  • Invited
• [Presentation] 深層学習による生体内微小環境の新次元俯瞰 (2022)
  • Author(s): 島村 徹平
  • Organizer: 第45回日本分子生物学会年会ワークショップ
  • Invited
• [Presentation] 深層学習で細胞社会を読み解く (2022)
  • Author(s): 島村 徹平
  • Organizer: 第45回日本分子生物学会年会フォーラム
  • Invited
• [Presentation] 深層学習による生体内微小環境の新次元俯瞰 (2022)
  • Author(s): 島村 徹平
  • Organizer: LINK-Jセミナー
  • Invited
• [Presentation] 深層学習による生体内微小環境の新次元俯瞰 (2022)
  • Author(s): 島村 徹平
  • Organizer: 第95回日本生化学会大会企画シンポジウム
  • Invited
• [Presentation] 深層学習による生体内微小環境の新次元俯瞰 (2022)
  • Author(s): 島村 徹平
  • Organizer: 第60回日本癌治療学会学術集会会長企画シンポジウム
  • Invited
• [Presentation] Estimating fluctuations in cell state dynamics and predicting fate bifurcations under influenza infection using deep learning (2022)
  • Author(s): 島村 徹平
  • Organizer: 第20回あわじ感染と免疫国際フォーラム
  • Int'l Joint Research / Invited
• [Presentation] A new modality for elucidating tumor microenvironment using deep learning (2022)
  • Author(s): 島村 徹平
  • Organizer: 第81回日本癌学会学術総会
  • Invited
• [Presentation] 細胞間コミュニケーションを読み解くためのデータ科学 (2022)
  • Author(s): 島村徹平
  • Organizer: 第6回理論免疫学ワークショップ
  • Invited
• [Presentation] データから読み解く生命医科学 (2022)
  • Author(s): 島村徹平
  • Organizer: 脳神経内科医のためのバイオインフォマティクス・ハンズオン 2021
  • Invited
• [Presentation] Deep learning to decipher cell dynamics and cell-cell interactions (2021)
  • Author(s): 島村徹平
  • Organizer: 第44回日本分子生物学会年会
  • Invited
• [Presentation] 一細胞マルチモーダル情報をデータとモデルから読み解く (2021)
  • Author(s): 島村徹平
  • Organizer: 産業技術研究所人工知能研究センター第51回AIセミナー
  • Invited
• [Presentation] 細胞間コミュニケーションを読み解く深層学習 (2021)
  • Author(s): 島村徹平
  • Organizer: 第94回日本生化学会大会
  • Invited
• [Presentation] Modeling cell population dynamics and cell-to-cell communication from single-cell multi-omics data (2021)
  • Author(s): 島村徹平
  • Organizer: 第80回日本癌学会学術総会
  • Invited
• [Presentation] データとモデルが駆動する生命科学 (2021)
  • Author(s): 島村徹平
  • Organizer: 第32回高遠・分子細胞生物学シンポジウム
  • Invited
• [Presentation] シングルセルオミクス解析のためのAI技術の最新動向 (2021)
  • Author(s): 島村徹平
  • Organizer: 第39回内分泌代謝学サマーセミナー
  • Invited
• [Presentation] 細胞集団のダイナミクスを捉えるためのベイズモデリング (2021)
  • Author(s): 島村徹平
  • Organizer: 第5回理論免疫学ワークショップ
  • Invited
• [Presentation] がん研究における一細胞解析のためのモデリング・AI 技術の最新動向 (2020)
  • Author(s): 島村徹平
  • Organizer: 第79回日本癌学会学術総会
  • Invited
• [Presentation] 臓器連関トランスオミクス解析のためのベイズモデリング (2020)
  • Author(s): 島村徹平
  • Organizer: 第93回日本生化学会大会
  • Invited
• [Presentation] 今こそ知りたい！行列因子分解～ゼロから始めるマルチオミクス解析～ (2020)
  • Author(s): 島村徹平
  • Organizer: 代謝統合オミクス若手技術セミナー
  • Invited
• [Book] 実験医学別冊最強のステップUPシリーズ 空間オミクス解析スタートアップ実践ガイド、空間トランスクリプトームに基づく細胞間相互作用ネットワークの解析技術 (2022)
  • Author(s): 小嶋泰弘、島村徹平
  • Total Pages: 244
  • Publisher: 羊土社
  • ISBN: 9784758122610