The integrated multi-omics analysis of nontuberculous mycobacteria using neural network algorithms to construct a predictive model of the pathological features

2019 Fiscal Year Research-status Report

• Project/Area Number: 18KT0019
• Research Institution: Niigata University
• Principal Investigator: 菊地 利明 新潟大学, 医歯学系, 教授 (10280926)
• Co-Investigator(Kenkyū-buntansha): 阿部 貴志 新潟大学, 自然科学系, 准教授 (30390628)
• Project Period (FY): 2018-07-18 – 2021-03-31
• Keywords: 非結核性抗酸菌 / オミックス解析 / 一括学習型自己組織化マップ / 深層学習

Outline of Annual Research Achievements

非結核性抗酸菌 (NTM) は環境中に広く生息しており、その吸入曝露によって、慢性呼吸器感染症であるNTM症を発症する。このNTM症の臨床上課題は、病態分類が不明確な点である。感染症は一般に、病原微生物と宿主との相互関係によって成立する。そこで「NTM症患者の起因菌の性状は、菌株固有の性状に加え、患者の病態も反映しており、起因菌から病態を分類できるのではないか？さらに、その分類された患者群から病態的特徴を明らかにし、起因菌から病態を予測できるようになるのではないか？」という問いを掲げる。これに対する答えを求めて、本研究では、一括学習型自己組織化マップ (BLSOM) と深層学習の二種類の神経回路網アルゴリズムを用いて、NTM症患者からの病態と起因菌のバイオデータを解析し、NTM症の病態分類群とその特徴を明らかにして、その病態を起因菌から予測する数理モデルを構築する。研究初年度の昨年度は、患者病態データの収集を主に行い、所属研究機関 (新潟大学) の倫理委員会で承認を受けた研究計画(承認番号：2016-0106)に従って、診療情報 (年齢、性別、生活歴、既往歴、現病歴、臨床検査値、X線/CT画像、治療経過、予後) に加え、炎症性因子 (38種類のサイトカインと鉄代謝マーカー) の血中濃度を、患者病態データとして収集を進めた。これを受け、研究二年目に当たる今年度は、NTMのゲノムデータの収集を行った。NTMのゲノムシークエンサーデータをマルチプレックスのシングルエンド法で解析したところ、約5 MbのNTMのゲノムに対し、平均2,574 Mbのシークエンスデータが得られた。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

研究初年度の昨年度は、患者病態データの収集を主に行い、所属研究機関 (新潟大学) の倫理委員会で承認を受けた研究計画(承認番号：2016-0106)に従って、診療情報 (年齢、性別、生活歴、既往歴、現病歴、臨床検査値、X線/CT画像、治療経過、予後) に加え、炎症性因子 (38種類のサイトカインと鉄代謝マーカー) の血中濃度を、患者病態データとして収集を進めた。これを受け、研究二年目に当たる今年度は、NTMのゲノムデータの収集を行った。NTMのゲノムシークエンサーデータをマルチプレックスのシングルエンド法で解析したところ、約5 MbのNTMのゲノムに対し、平均2,574 Mbのシークエンスデータが得られた。

Strategy for Future Research Activity

最終年度に当たる来年度は、これまで収集した患者病態データとNTMのゲノムデータを用いて、NTM症の病態分類群とその特徴を明らかにし、その病態を起因菌から予測する数理モデルを構築していく。

Causes of Carryover

NTMのゲノムデータの収集を、計画より効率的に行うことができたために、次年度使用額が生じた。生じた次年度使用額を2020年度当初予算額と合わせて使用することにより、計画より詳細な解析を行う予定である。

Research Products

• [Journal Article] COVID-19 outbreak: An elusive enemy (2020)
  • Author(s): Kikuchi T.
  • Journal Title: Respir Investig Volume: 58 Pages: 225-226
  • DOI: 10.1016/j.resinv.2020.03.006
  • Peer Reviewed / Open Access
• [Journal Article] Distribution of Legionella species and serogroups in patients with culture-confirmed Legionella pneumonia (2020)
  • Author(s): Miyashita N, Higa F, Aoki Y, Kikuchi T, Seki M, Tateda K, Maki N, Uchino K, Ogasawara K, Kiyota H, Watanabe A.
  • Journal Title: J Infect Chemother Volume: 26 Pages: 411-417
  • DOI: 10.1016/j.jiac.2019.12.016
  • Peer Reviewed / Open Access
• [Journal Article] A study of factors related to asthma exacerbation using a questionnaire survey in Niigata Prefecture, Japan (2020)
  • Author(s): Ueno H, Koya T, Hasegawa T, Hayashi M, Yoshizawa K, Suzuki E, Kikuchi T; the Niigata Asthma Treatment Study Group.
  • Journal Title: Asian Pac J Allergy Immunol Volume: 38 Pages: 108-113
  • DOI: 10.12932/AP-080918-0404
  • Peer Reviewed / Open Access
• [Journal Article] Cysteinyl Leukotriene synthesis via Phospholipase A2 Group IV Mediates Exercise-induced Bronchoconstriction and Airway Remodeling (2020)
  • Author(s): Ueno Hiroshi、Koya Toshiyuki、Takeuchi Hiroyuki、Tsukioka Keisuke、Saito Akira、Kimura Yosuke、Hayashi Masachika、Watanabe Satoshi、Hasegawa Takashi、Arakawa Masaaki、Kikuchi Toshiaki
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: in press Pages: in press
  • DOI: 10.1165/rcmb.2019-0325OC
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic significance of the radiologic features of pneumonitis induced by anti‐PD‐1 therapy (2020)
  • Author(s): Watanabe Satoshi、Ota Takeshi、Hayashi Masachika、Ishikawa Hiroyuki、Otsubo Aya、Shoji Satoshi、Nozaki Koichiro、Ichikawa Kosuke、Kondo Rie、Miyabayashi Takao、Miura Satoru、Tanaka Hiroshi、Abe Tetsuya、Okajima Masaaki、Terada Masaki、Ishida Takashi、Iwashima Akira、Sato Kazuhiro、Yoshizawa Hirohisa、Kikuchi Toshiaki
  • Journal Title: Cancer Medicine Volume: 9 Pages: 3070～3077
  • DOI: 10.1002/cam4.2974
  • Peer Reviewed
• [Journal Article] Comparison of Cytokine Profiles Between anti-ARS Antibody-Positive Interstitial Lung Diseases and Those With anti-MDA-5 Antibodies. (2020)
  • Author(s): Asakawa K, Yoshizawa K, Aoki A, Kimura Y, Tanaka T, Ohashi K, Hayashi M, Kikuchi T, Sato S, Takada T.
  • Journal Title: Clin Rheumatol. Volume: in press Pages: in press
  • DOI: 10.1007/s10067-020-04984-x.
  • Peer Reviewed
• [Journal Article] ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non?Small Cell Lung Cancer (2020)
  • Author(s): Okura N, Nishioka N, Yamada T, Taniguchi H, Tanimura K, Katayama Y, Yoshimura A, Watanabe S, Kikuchi T, Shiotsu S, Kitazaki T, Nishiyama A, Iwasaku M, Kaneko Y, Uchino J, Uehara H, Horinaka M, Sakai T, Tanaka K, Kozaki R, Yano S, Takayama K.
  • Journal Title: Clinical Cancer Research Volume: 26 Pages: 2244～2256
  • DOI: 10.1158/1078-0432.CCR-19-2321
  • Peer Reviewed / Open Access
• [Journal Article] Serum Anti-Interferon-γ autoantibody 1 titer as a potential biomarker of disseminated non-tuberculous mycobacterial infection. (2020)
  • Author(s): Yoshizawa K, Aoki A, Shima K, Tanabe Y, Koya T, Hasegawa T, Kikuchi T, Sakagami T.
  • Journal Title: J Clin Immunol. Volume: 40 Pages: 399～405
  • DOI: 10.1007/s10875-020-00762-1
  • Peer Reviewed / Open Access
• [Journal Article] First-line osimertinib treatment in patients with lung squamous cell carcinoma harboring active epidermal growth factor receptor mutations (2020)
  • Author(s): Shoji Satoshi、Watanabe Satoshi、Takamura Kaori、Umezu Hajime、Kikuchi Toshiaki
  • Journal Title: Lung Cancer Volume: 140 Pages: 113～115
  • DOI: 10.1016/j.lungcan.2019.11.012
  • Peer Reviewed
• [Journal Article] Characterization of low adherence population in asthma patients from Japan using Adherence Starts with Knowledge-12 (2020)
  • Author(s): Kimura Yuka、Koya Toshiyuki、Hasegawa Takashi、Ueno Hiroshi、Yoshizawa Kazutaka、Kimura Yosuke、Hayashi Masachika、Watanabe Satoshi、Kikuchi Toshiaki
  • Journal Title: Allergology International Volume: 69 Pages: 61～65
  • DOI: 10.1016/j.alit.2019.07.006
  • Peer Reviewed
• [Journal Article] Association of upper and lower airway eosinophilic inflammation with response to omalizumab in patients with severe asthma (2020)
  • Author(s): Kurokawa Makoto、Koya Toshiyuki、Takeuchi Hiroyuki、Hayashi Masachika、Sakagami Takuro、Ishioka Kojiro、Gon Yasuhiro、Hasegawa Takashi、Kikuchi Toshiaki
  • Journal Title: Journal of Asthma Volume: 57 Pages: 71～78
  • DOI: 10.1080/02770903.2018.1541357
  • Peer Reviewed
• [Journal Article] Should pulmonologists be gatekeepers or supporters for preoperative patients? (2020)
  • Author(s): Hokari Satoshi、Kikuchi Toshiaki
  • Journal Title: Respiratory Investigation Volume: 58 Pages: 4～6
  • DOI: 10.1016/j.resinv.2019.09.001
  • Peer Reviewed
• [Journal Article] Comparative analysis of TTF‐1 binding DNA regions in small‐cell lung cancer and non‐small‐cell lung cancer (2019)
  • Author(s): Hokari Satoshi、Tamura Yusuke、Kaneda Atsushi、Katsura Akihiro、Morikawa Masato、Murai Fumihiko、Ehata Shogo、Tsutsumi Shuichi、Ishikawa Yuichi、Aburatani Hiroyuki、Kikuchi Toshiaki、Miyazono Kohei、Koinuma Daizo
  • Journal Title: Molecular Oncology Volume: 14 Pages: 277～293
  • DOI: 10.1002/1878-0261.12608
  • Peer Reviewed
• [Journal Article] Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study (2019)
  • Author(s): Shoji Satoshi、Hosojima Michihiro、Kabasawa Hideyuki、Kondo Rie、Miura Satoru、Watanabe Satoshi、Aoki Nobumasa、Kaseda Ryohei、Kuwahara Shoji、Tanabe Naohito、Hirayama Yoshiaki、Narita Ichiei、Kikuchi Toshiaki、Kagamu Hiroshi、Saito Akihiko
  • Journal Title: BMC Cancer Volume: 19 Pages: 1170
  • DOI: 10.1186/s12885-019-6398-2
  • Peer Reviewed
• [Journal Article] Efficacy of EGFR‐TKIs with or without upfront brain radiotherapy for EGFR ‐mutant NSCLC patients with central nervous system metastases (2019)
  • Author(s): Saida Yu、Watanabe Satoshi、Abe Tetsuya、Shoji Satoshi、Nozaki Koichiro、Ichikawa Kosuke、Kondo Rie、Koyama Kenichi、Miura Satoru、Tanaka Hiroshi、Okajima Masaaki、Terada Masaki、Ishida Takashi、Tsukada Hiroki、Makino Masato、Iwashima Akira、Sato Kazuhiro、Matsumoto Naoya、Yoshizawa Hirohisa、Kikuchi Toshiaki
  • Journal Title: Thoracic Cancer Volume: 10 Pages: 2106～2116
  • DOI: 10.1111/1759-7714.13189
  • Peer Reviewed / Open Access
• [Journal Article] Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan (2019)
  • Author(s): Yamaba Yusuke、Ito Yutaka、Suzuki Katsuhiro、Kikuchi Toshiaki、Ogawa Kenji、Fujiuchi Satoru、Hasegawa Naoki、Kurashima Atsuyuki、Higuchi Takeshi、Uchiya Kei-ichi、Watanabe Akira、Niimi Akio
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Pages: 995～1000
  • DOI: 10.1016/j.jiac.2019.05.028
  • Peer Reviewed / Open Access
• [Journal Article] Retrospective analysis of antitumor effects and biomarkers for nivolumab in NSCLC patients with EGFR mutations (2019)
  • Author(s): Sato Miyuki、Watanabe Satoshi、Tanaka Hiroshi、Nozaki Koichiro、Arita Masashi、Takahashi Miho、Shoji Satoshi、Ichikawa Kosuke、Kondo Rie、Aoki Nobumasa、Hayashi Masachika、Ohshima Yasuyoshi、Koya Toshiyuki、Ohashi Riuko、Ajioka Yoichi、Kikuchi Toshiaki
  • Journal Title: PLOS ONE Volume: 14 Pages: e0215292
  • DOI: 10.1371/journal.pone.0215292
  • Peer Reviewed / Open Access
• [Journal Article] Validation of a diagnostic score model for the prediction of Legionella pneumophila pneumonia (2019)
  • Author(s): Miyashita Naoyuki、Horita Nobuyuki、Higa Futoshi、Aoki Yosuke、Kikuchi Toshiaki、Seki Masafumi、Tateda Kazuhiro、Maki Nobuko、Uchino Kazuhiro、Ogasawara Kazuhiko、Kiyota Hiroshi、Watanabe Akira
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Pages: 407～412
  • DOI: 10.1016/j.jiac.2019.03.009
  • Peer Reviewed
• [Journal Article] Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer. (2019)
  • Author(s): Yamada T, Hirai S, Katayama Y, Yoshimura A, Shiotsu S, Watanabe S, Kikuchi T, Hirose K, Kubota Y, Chihara Y, Harada T, Tanimura K, Takeda T, Tamiya N, Kaneko Y, Uchino J, Takayama K.
  • Journal Title: Cancer Med. Volume: 8 Pages: 1521～1529
  • DOI: 10.1002/cam4.2037.
  • Peer Reviewed / Open Access
• [Journal Article] Multiplex cytokine analysis in Mycobacterium avium complex lung disease: relationship between CXCL10 and poor prognostic factors (2019)
  • Author(s): Bamba Yuuki、Moro Hiroshi、Aoki Nobumasa、Koizumi Takeshi、Ohshima Yasuyoshi、Watanabe Satoshi、Sakagami Takuro、Koya Toshiyuki、Takada Toshinori、Kikuchi Toshiaki
  • Journal Title: BMC Infectious Diseases Volume: 19 Pages: 263
  • DOI: 10.1186/s12879-019-3888-4
  • Peer Reviewed / Open Access
• [Journal Article] AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells (2019)
  • Author(s): Taniguchi H, Yamada T, Wang R, Tanimura K, Adachi Y, Nishiyama A, Tanimoto A, Takeuchi S, Araujo L, Boroni M, Yoshimura A, Shiotsu S, Matsumoto I, Watanabe S, Kikuchi T, Miura S, Tanaka H, Kitazaki T, Yamaguchi H, Mukae H, Uchino J, Uehara H, Takayama K, Yano S.
  • Journal Title: Nature Communications Volume: 10 Pages: 259
  • DOI: 10.1038/s41467-018-08074-0
  • Peer Reviewed / Open Access
• [Journal Article] An α-Lipoic acid derivative, and anti-ROS agent, prevents the acquisition of multi-drug resistance in clinical isolates of Pseudomonas aeruginosa (2019)
  • Author(s): Hayakawa Sachiko、Kawamura Masato、Sato Takumi、Hirano Taizou、Kikuchi Toshiaki、Watanabe Akira、Fujimura Shigeru
  • Journal Title: Journal of Infection and Chemotherapy Volume: 25 Pages: 28～33
  • DOI: 10.1016/j.jiac.2018.10.003
  • Peer Reviewed / Open Access
• [Journal Article] Baloxavir heralds a new era in influenza virus biology (2019)
  • Author(s): Kikuchi Toshiaki、Watanabe Akira
  • Journal Title: Respiratory Investigation Volume: 57 Pages: 1～2
  • DOI: 10.1016/j.resinv.2018.10.002
  • Peer Reviewed
• [Journal Article] Pneumocystis pneumonia in HIV-1-infected patients (2019)
  • Author(s): Shibata Satoshi、Kikuchi Toshiaki
  • Journal Title: Respiratory Investigation Volume: 57 Pages: 213～219
  • DOI: 10.1016/j.resinv.2019.01.009
  • Peer Reviewed
• [Presentation] 世界の中のニッポン 日本の結核は再度増えるのか (2019)
  • Author(s): 菊地利明
  • Organizer: 第59回日本呼吸器学会学術講演会
  • Invited
• [Presentation] 肺MAC症の病型 FC型とNB型の根本的な違いは何か (2019)
  • Author(s): 菊地利明
  • Organizer: 第94回日本結核病学会総会
  • Invited
• [Presentation] The Relationship Between Social Capital and Asthma Control. (2019)
  • Author(s): A. Saito, T. Hasegawa, T. Koya, S. Nagumo, Y.Nishiyama, K. Yoshizawa, H. Ueno, Y. Kimura, M. Hayashi, Y. Shobugawa, R. Saito, T. Kikuchi.
  • Organizer: American Thoracic Society International Conference
  • Int'l Joint Research
• [Presentation] The Effect of Weight Loss on Bronchial Asthma Model. (2019)
  • Author(s): Y. Nishiyama, T. Koya, T. Hasegawa, H. Ueno, K. Yoshizawa, A. Saito, S. Nagumo, Y. Kimura, M. Hayashi, T. Kikuchi.
  • Organizer: American Thoracic Society International Conference
  • Int'l Joint Research
• [Presentation] Prognostic significance of radiologic features of pneumonitis induced by anti-PD-1 therapy. (2019)
  • Author(s): S. Watanabe, T. Ota, M. Hayashi, H. Ishikawa, T. Miyabayashi, M. Terada, K. Sato, T. Ishida, H. Tanaka, A. Iwashima, S. Shoji, K. Nozaki, K. Ichikawa, R. Kondo, H. Yoshizawa, T. Kikuchi
  • Organizer: 2019 American Society of Clinical Oncology Annual Meeting
  • Int'l Joint Research
• [Book] 今日の治療指針 2020年版 (2020)
  • Author(s): 菊地利明
  • Total Pages: 2115
  • Publisher: 医学書院
  • ISBN: 978-4-260-03939-0
• [Book] 診療ガイドライン UP-TO-DATE 2020-2021 (2020)
  • Author(s): 茂呂寛、菊地利明
  • Total Pages: 1060
  • Publisher: メディカルレビュー社
  • ISBN: 978-4-7792-2253-5
• [Book] 今日の処方（改訂第6版） (2019)
  • Author(s): 菊地利明
  • Total Pages: 904
  • Publisher: 南江堂
  • ISBN: 4524251197
• [Book] 呼吸器疾患最新の治療2019-2020 (2019)
  • Author(s): 小泉健、菊地利明
  • Total Pages: 534
  • Publisher: 南江堂
  • ISBN: 978-4-524-24557-4
• [Remarks] 新潟大学大学院医歯学総合研究科 呼吸器・感染症内科学分野
  • URL: https://www.med.niigata-u.ac.jp/resp/welcome.html