Constructing a Disease-Related Microbiome Atlas for Advancing Understanding of Microbial Functionality

• Project/Area Number: 20K21832
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 62:Applied informatics and related fields
• Research Institution: Nagoya University
• Principal Investigator: Shimamura Teppei 名古屋大学, 医学系研究科, 教授 (00623943)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: メタゲノム / マルチオミクス解析 / ベイズモデリング / トピックモデル / 因子分解モデル / 深層生成モデル

Outline of Research at the Start

本研究課題では、最先端のオミクス計測技術とベイズ推論による最新の解析技術を駆使し、様々な疾患の原因となる細菌叢を効率的に探索するための「疾患関連細菌叢アトラス」を創出する。本研究で行うユニークなモデリング技術の開発とそれによる斬新なデータベースの構築により、細菌叢の大海原で研究者が遭難しないように「予測地図」を提供することが主たる目的である。細菌叢の機能解析への障壁を取り去り、我が国の強みを生かした研究を推進することで国際産業競争力を強化するとともに、国民のQOL、細菌叢を利用した健康・医療産業の活性化にも大きく貢献することが期待される。

Outline of Final Research Achievements

In this study, we utilize Bayesian modeling techniques, previously developed by the applicant, as the technical cornerstone to address challenges in microbiome analysis such as the management of infrequently occurring microbial species and the consideration of inter-individual variability. Targeting the human microbiota, we develop Bayesian modeling techniques aimed at elucidating the functionalities of the microbiota and its correlation with health and disease. Concurrently, we construct a suite of analytical tools enabling the analysis of microbiome data from public disease-related cohort studies, and integrate these into a comprehensive database, the 'Disease-Related Microbiome Atlas'.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、世界中に登録された公共の膨大なコホート研究の細菌叢データ（衛星地図）と最先端のベイズモデリング技術（GPS）の２つの強力なツールを駆使することによって、細菌叢の大海原で研究者が遭難しないように「予測地図」を提供することが主たる目的である。本研究の活用により、細菌叢の機能解析への障壁を取り去り、国民のQOL、細菌叢を利用した健康・医療産業の活性化にも大きく貢献す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: 22068-22068
  • 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, Mimori K(28番目）,他26名
  • Journal Title: Cell Reports Volume: 42 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 (2023)
  • 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