Bioinformatics analysis of disease attractors and gene regulatory networks of Alzheimer's disease

• Project/Area Number: 16K00385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Tohoku University
• Principal Investigator: Ogishima Soichi 東北大学, 東北メディカル・メガバンク機構, 教授 (40447496)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 生命情報 / 疾患アトラクター / アルツハイマー病 / 遺伝子調節ネットワーク / アルツハイマー

Outline of Final Research Achievements

We inferred attractors of disease state of Alzheimer’s disease (AD), conducted trajectory analysis of those attractors, and analyzed gene regulatory network forming those attractors. We then developed the algorithm to detect complex gene-environment (GxE) interactions causing AD. Using gene expression data of AD samples, we inferred probabilistic potentials of AD samples in the state space of AD gene expression data. We also inferred the corresponding gene regulatory network to AD attractors on probabilistic potentials.

Academic Significance and Societal Importance of the Research Achievements

本研究は遺伝要因、環境要因が複雑に相互作用して発症する多因子疾患の機序の解明に向けて、アルツハイマー病において遺伝要因、生活習慣や環境暴露等の環境要因の複雑な相互作用(G×E)の推定手法の開発を行い、遺伝子発現の状態空間における細胞集団の遺伝子発現ポテンシャルの推定、疾患アトラクターの推定、疾患アトラクターを形成する遺伝子調節ネットワークの解析を行った。遺伝要因、環境要因が複雑に相互作用して発症する多因子疾患の機序を解明することに寄与する、新たな情報学的な手法を開発した。

Research Products

• [Journal Article] Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals (2019)
  • Author(s): Yamaguchi-Kabata, Y.,（途中略）,Koshiba, S., （途中略）, Tohoku Medical Megabank Project Study Group.（合計１9名、本研究者は５番目）
  • Journal Title: Hum. Genet. Volume: 印刷中 Issue: 4 Pages: 389-409
  • DOI: 10.1007/s00439-019-01998-7
  • Peer Reviewed / Open Access
• [Journal Article] Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population (2019)
  • Author(s): Tanikawa Chizu、...、Ogishima Soichi、...、Matsuda Koichi
  • Journal Title: Journal of the American Society of Nephrology Volume: 印刷中 Issue: 5 Pages: 855-864
  • DOI: 10.1681/asn.2018090942
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serum magnesium and calcium levels in relation to ischemic stroke (2019)
  • Author(s): Larsson Susanna C.、Traylor Matthew、Burgess Stephen、Boncoraglio Giorgio B.、Jern Christina、Micha?lsson Karl、Markus Hugh S.、for the MEGASTROKE project of the International Stroke Genetics Consortium
  • Journal Title: Neurology Volume: 92 Issue: 9
  • DOI: 10.1212/wnl.0000000000007001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Maternity Log study: A longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy (2019)
  • Author(s): Sugawara J, Ochi D, Yamashita R, Yamauchi T, Saigusa D, Wagata M, Obara T, Ishikuro M, Tsunemoto Y, 18名略, Hiyama S, Nagasaki M
  • Journal Title: BMJ Open Volume: 9 Issue: 2 Pages: e025939-e025939
  • DOI: 10.1136/bmjopen-2018-025939
  • Peer Reviewed / Open Access
• [Journal Article] Susceptibility Loci for Tanning Ability in the Japanese?Population Identified by a?Genome-Wide?Association Study from the Tohoku Medical Megabank Project Cohort Study (2019)
  • Author(s): Shido Kosuke、Kojima Kaname、Yamasaki Kenshi、Hozawa Atsushi、Tamiya Gen、Ogishima Soichi、Minegishi Naoko、Kawai Yosuke、Tanno Kozo、Suzuki Yoichi、Nagasaki Masao、Aiba Setsuya
  • Journal Title: Journal of Investigative Dermatology Volume: epub Issue: 7 Pages: 1605-1608.e13
  • DOI: 10.1016/j.jid.2019.01.015
  • Peer Reviewed / Open Access
• [Journal Article] Genome analyses for the Tohoku Medical Megabank Project towards establishment of personalized healthcare (2018)
  • Author(s): Yasuda Jun、Kinoshita Kengo、et al.,
  • Journal Title: The Journal of Biochemistry Volume: 165 Issue: 2 Pages: 139
  • DOI: 10.1093/jb/mvy096
  • NAID: 40021809939
  • Peer Reviewed / Open Access
• [Journal Article] Authentication of Patients and Participants in Health Information Exchange and Consent for Medical Research: A Key Step for Privacy Protection, Respect for Autonomy, and Trustworthiness (2018)
  • Author(s): Kogetsu Atsushi、Ogishima Soichi、Kato Kazuto
  • Journal Title: Frontiers in Genetics Volume: 9 Pages: 167-167
  • DOI: 10.3389/fgene.2018.00167
  • Peer Reviewed / Open Access
• [Journal Article] Omics research project on prospective cohort studies from the Tohoku Medical Megabank Project (2018)
  • Author(s): Koshiba, S., （途中略）, Yamamoto, M.（合計２１名、本研究者は１番目）
  • Journal Title: Genes Cells Volume: 23 Issue: 6 Pages: 406
  • DOI: 10.1111/gtc.12588
  • Peer Reviewed / Open Access
• [Journal Article] Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes (2018)
  • Author(s): Malik R, Chauhan G, Traylor M, Minegishi N, AFGen Consortium,BioBank Japan Cooperative Hospital Group; MEGASTROKE Consortium
  • Journal Title: Nat Genet Volume: 50 Issue: 4 Pages: 524-537
  • DOI: 10.1038/s41588-018-0058-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of reported pathogenic variants and their frequencies in a Japanese population based on a whole-genome reference panel of 2049 individuals article (2018)
  • Author(s): Y Yamaguchi-Kabata, J Yasuda, O Tanabe, Y Suzuki, H Kawame, N Fuse, M Nagasaki, Y Kawai, K Kojima, F Katsuoka, S Saito, I Danjoh, I Motoike, R Yamashita, S Koshiba, D Saigusa, G Tamiya, S Kure, N Yaegashi, Y Kawaguchi, F Nagami, S Kuriyama, J Sugawara, N Minegishi, A Hozawa, T Takai-Igarashi, K Kinoshita, M Yamamoto.
  • Journal Title: Journal of Human Genetics. Volume: 63 Issue: 2 Pages: 213
  • DOI: 10.1038/s10038-017-0347-1
  • Peer Reviewed / Open Access
• [Journal Article] Identification of six novel genetic loci associated with atrial fibrillation in Japanese population. (2017)
  • Author(s): Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT, AFGen Consortium, Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M, Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M, Ito K, Kamatani Y, Tanaka T.
  • Journal Title: Nature Genetics Volume: - Issue: 6 Pages: 953-958
  • DOI: 10.1038/ng.3842
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design (2017)
  • Author(s): Takai-Igarashi T, Kinoshita K, Nagasaki M, Ogishima S, Nakamura N, Nagase S, Nagaie S, Saito T, Nagami F, Minegishi N, Suzuki Y, Suzuki K, Hashizume H, Kuriyama S, Hozawa A, Yaegashi N, Kure S, Tamiya G, Kawaguchi Y, Tanaka H, Yamamoto M
  • Journal Title: BMC Med Inform Decis Mak Volume: 17 Issue: 1 Pages: 100-100
  • DOI: 10.1186/s12911-017-0494-5
  • Peer Reviewed / Open Access
• [Journal Article] FANTOM5 CAGE profiles of human and mouse samples (2017)
  • Author(s): Noguchi Shuhei、Arakawa Takahiro、Ogishima Soichi、ほか
  • Journal Title: Sci Data Volume: 4 Issue: 1 Pages: 170112-170112
  • DOI: 10.1038/sdata.2017.112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Human Phenotype Ontology in 2017. (2017)
  • Author(s): Kohler S, Vasilevsky NA, Engelstad M, Foster E, McMurry J, Ayme S, Baynam G, Bello SM, ... Ogishima S, ...Haendel M.
  • Journal Title: Nucleic Acids Res Volume: 45(D1) Issue: D1 Pages: D865-D876
  • DOI: 10.1093/nar/gkw1039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Tohoku Medical Megabank Project: Design and Mission (2016)
  • Author(s): Kuriyama S, Yaegashi N, et al. (Tamiya G; 11th in 58 authors)
  • Journal Title: Journal of Epidemiology Volume: 26 Issue: 9 Pages: 493-511
  • DOI: 10.2188/jea.JE20150268
  • NAID: 130005409018
  • ISSN: 0917-5040, 1349-9092
  • Peer Reviewed / Open Access
• [Journal Article] The structural origin of metabolic quantitative diversity (2016)
  • Author(s): Koshiba S, Motoike I, Kojima K, Hasegawa T, Shirota M, Saito T, Saigusa D, Danjoh I, Katsuoka F, Ogishima S, ... Yamamoto M.
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 31463-31463
  • DOI: 10.1038/srep31463
  • URL: https://pure.teikyo.jp/en/publications/f23f66dd-859e-4088-8e53-de40d99cc561
  • Peer Reviewed / Open Access
• [Journal Article] The Pre-Eclampsia Ontology: A Disease Ontology Representing the Domain Knowledge Specific to Pre-Eclampsia. (2016)
  • Author(s): Mizuno S, Ogishima S, Nishigori H, Jamieson DG, Verspoor K, Tanaka H, Yaegashi N, Nakaya J.
  • Journal Title: PLoS One Volume: 11(10) Issue: 10 Pages: e0162828-e0162828
  • DOI: 10.1371/journal.pone.0162828
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Development of biobank network in Japan (2019)
  • Author(s): Soichi Ogishima
  • Organizer: AMED-GA4GH GEM Japan Workshop 2019 Sendai Symposium
• [Presentation] Integrated database "db TMM" for genomic prospective cohort study in Tohoku Medical Megabank Toward personalized healthcare (2019)
  • Author(s): 荻島創一
  • Organizer: 生物試料の保管と活用に関するワークショップ
  • Invited
• [Presentation] データ管理と共有・クラウドの利活用 (2019)
  • Author(s): 荻島創一
  • Organizer: 第2回バイオメディカルデータサイエンティスト養成集中講座
  • Invited
• [Presentation] Enabling genomic & phenotypic data sharing for the benefit of human health (2018)
  • Author(s): Soichi Ogishima
  • Organizer: BioHackathon 2018
  • Invited
• [Presentation] データベースはこれからの医療をこう変えてゆくか「データシェアリングの国外の動向と東北メディカル・メガバンク統合データベースdbTMMの取り組み」 (2018)
  • Author(s): 荻島創一
  • Organizer: 日本人類遺伝学会第63回大会
  • Invited
• [Presentation] AMEDスポンサードセッション・バイオバンクの利活用促進と倫理的・法的・社会的課題（ELSI）「ゲノム医療実現推進のためのバイオバンク利活用促進に向けたバイオバンク・ネットワーク構 築と運用支援に関する研究開発」 (2018)
  • Author(s): 荻島創一
  • Organizer: 情報計算化学生物学会2018年大会
• [Presentation] 第2回オミックスを原理的なところから考える-「生命」と多様性を共存させる原理は？- (2018)
  • Author(s): 荻島創一
  • Organizer: 情報計算化学生物学会2018年大会
• [Presentation] バイオバンクのネットワーク化で何が変わるのか？「バイオバンクのネットワーク化と横断検索」 (2018)
  • Author(s): 荻島創一
  • Organizer: 第4回クリニカルバイオバンク学会シンポジウム
  • Invited
• [Presentation] 東北メディカル・メガバンク計画における統合データベースdbTMMの構築の現状と今後ー診療情報に基づくフェノタイピングによる追跡調査へ向けてー (2018)
  • Author(s): 荻島創一
  • Organizer: いわて東北メディカル・メガバンク機構講演会
  • Invited
• [Presentation] Conduct the QOL survey using J-RARE - NANBYO Patients’ Data Platform led by patients (2018)
  • Author(s): Nishimura Y, Emoto S, Nishimura K, Iwasaki M, J-RARE patient organization groups, Yoshizawa G and Ogishima S
  • Organizer: ECRD 2018
• [Presentation] バイオバンク横断検索のプロトタイプ開発 -バイオバンクの保管試料・情報の「見える化」とワンストップでの横断検索 (2018)
  • Author(s): 荻島創一
  • Organizer: 第3回バイオバンク連絡会
  • Invited
• [Presentation] 個人情報保護法改正とゲノムデータの取扱い、国内外の動向 (2018)
  • Author(s): 荻島創一
  • Organizer: バイオメディカルデータサイエンティスト養成集中講座
  • Invited
• [Presentation] ビッグデータ・AI・ゲノム・創薬 セッション －AIや各種統計解析手法を用いたビッグデータ解析によるゲノム創薬の最前線 (2017)
  • Author(s): 荻島創一
  • Organizer: 第15回日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] 診療情報の利活用によるフェノタイピングとHuman Phenotype Ontology（HPO） (2017)
  • Author(s): 荻島創一
  • Organizer: 第10回 Pharma AI Forum (PHAIFO)
  • Invited
• [Presentation] 前向きゲノムコホート研究へのNGSの貢献 (2017)
  • Author(s): 荻島創一
  • Organizer: Kobe NGS Day
  • Invited
• [Presentation] 東北メディカル・メガバンク計画の進捗と統合データベースdbTMMの構築 -診療情報に基づくフェノタイピングによる追跡調査へ向けて- (2017)
  • Author(s): 荻島創一
  • Organizer: 第80回徳島大学先端酵素学研究所糖尿病臨床・研究開発センター講演会
  • Invited
• [Presentation] ゲノム医療支援の人工知能の研究開発へ向けて：ゲノム医療とは？ (2017)
  • Author(s): 荻島創一
  • Organizer: 人工知能学会全国大会2017年度大会
• [Presentation] 東北メディカル・メガバンク計画の進捗状況と日本のバイオバンクのこれから (2017)
  • Author(s): 荻島創一
  • Organizer: 第3回クリニカルバイオバンク研究会
• [Presentation] 東北メディカル・メガバンク 共同研究および分譲申請について (2017)
  • Author(s): 荻島創一
  • Organizer: 第6回生命医薬情報学連合大会
• [Presentation] Development of Tohoku Medical Megabank Integrated Database ”dbTMM” and Knowledge-Base "kbTMM" (2017)
  • Author(s): Soichi Ogishima
  • Organizer: KI-Tohoku joint conference for international collaborations in Biobanking and Biochemistry (未来型医療拠点キックオフ 第二回カロリンスカ研究所・東北大学合同会議)
  • Int'l Joint Research
• [Presentation] ゲノム医療研究におけるPhenotyping (2017)
  • Author(s): 荻島創一
  • Organizer: 第37回医療情報学連合大会
• [Presentation] Network-based inference of signature genes of Alzheimer’s disease progression. (2017)
  • Author(s): Ogishima S, Tanaka H.
  • Organizer: AROB Workshop on Artificial Life and Robotics in Busan
  • Int'l Joint Research
• [Presentation] A method to associate all possible combinations of genetic and environmental factors using GxE landscape plot. (2017)
  • Author(s): Nagaie S, Ogishima S, Tanaka H.
  • Organizer: AROB Workshop on Artificial Life and Robotics in Busan
  • Int'l Joint Research
• [Presentation] Minimum common data set in cross-biobank search across biobanks in Japan. (2017)
  • Author(s): Morita M, Hirata M, Ikeda S, Tomida S, Imoto S, Ogishima S.
  • Organizer: Global Biobank Week 2017
  • Int'l Joint Research
• [Presentation] A novel method of phenotype similarities of rare-disease patients using gene-pathway-phenotype relationships. (2017)
  • Author(s): Ogishima S, Nagaie S.
  • Organizer: American Society of Human Genetics 2017
  • Int'l Joint Research
• [Presentation] 未来型の個別化予防の実現に向けて - 統合・知識データベースの構築 (2016)
  • Author(s): 荻島創一
  • Organizer: 関西経済連合会 ビッグデータ利活用促進に向けた講演会（大阪府・大阪市）
  • Place of Presentation: 関西経済連合会（大阪府・大阪市）
  • Invited
• [Book] ゲノム医療とゲノム創薬におけるビッグデータの活用「ヒトゲノム情報と創薬」 (2018)
  • Author(s): 荻島 創一
  • Total Pages: 4
  • Publisher: 癌と化学療法社
• [Book] ヒト疾患のデータベースとバイオバンク (2017)
  • Author(s): 山本雅之, 荻島創一（編著）他共著
  • Total Pages: 229
  • Publisher: 羊土社
• [Book] 改正個人情報保護法でゲノム研究はどう変わるか？-個人識別符号 ・ 要配慮情報としてのゲノムデータ (2017)
  • Author(s): 清水佳奈, 山本奈津子, 川嶋実苗, 片山俊明, 荻島創一
  • Total Pages: 6
  • Publisher: 羊土社