Large-scale Genomic Cohort Study by Deep Learning

• Project/Area Number: 16K08638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Tohoku University
• Principal Investigator: TAMIYA Gen 東北大学, 東北メディカル・メガバンク機構, 教授 (10317745)
• Co-Investigator(Kenkyū-buntansha): 植木 優夫 国立研究開発法人理化学研究所, 革新知能統合研究センター, 研究員 (10515860)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 遺伝統計学 / 人類遺伝学 / コホート研究 / 遺伝子×環境相互作用 / 深層学習 / ゲノム / 遺伝学 / 機械学習

Outline of Final Research Achievements

In large-scale genomic cohort studies, we have several hundreds or over thousand phenotype data from tens of thousands participants: health exam results, diseases outcome, blood test and imaging data, if any, metabolomics and proteomics data. The high dimensionality and correlation structure may become an obstacle in the statistical detection of the effect among genes, environments and their interactions. In this study, we utilized a framework of deep learning to flexibly extract features from the high dimensional data as health status variable that overcome the obstacle to be deciphering these effect.

Academic Significance and Societal Importance of the Research Achievements

現在、深層学習の研究は人工知能分野で活発に行われ、すでに多くのアルゴリズムが工夫され公開されている。本研究は、このような最先端の枠組みを遺伝学・ゲノム医学分野に応用して、大規模ゲノムコホートデータ解析の限界を克服し、より網羅的な遺伝統計学的分析手法を開発しているところが特色・独創的な点である。これにより、大規模ゲノムコホートデータを網羅的に用いた因子間相互作用解析手法が開発され、妥当な計算機資源で実行可能なソフトウェアとして整備される。このようなソフトウェアは、限られた研究施設でなくとも解析の実行を可能にし、大規模ゲノムコホート研究でのジレンマを打破するブレークスルーになると期待される。

Research Products

• [Journal Article] The prevalence of GALM mutations that cause galactosemia: A database of functionally evaluated variants (2019)
  • Author(s): Iwasawa Shinya、Kikuchi Atsuo、Wada Yoichi、Arai-Ichinoi Natsuko、Sakamoto Osamu、Tamiya Gen、Kure Shigeo
  • Journal Title: Molecular Genetics and Metabolism Volume: 印刷中 Issue: 4 Pages: 362-367
  • DOI: 10.1016/j.ymgme.2019.01.018
  • Peer Reviewed
• [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] Outlier detection for questionnaire data in biobanks (2019)
  • Author(s): Sakurai Rieko、Ueki Masao、Makino Satoshi、Hozawa Atsushi、Kuriyama Shinichi、Takai-Igarashi Takako、Kinoshita Kengo、Yamamoto Masayuki、Tamiya Gen
  • Journal Title: International Journal of Epidemiology Volume: 印刷中 Issue: 4 Pages: 1305-1315
  • DOI: 10.1093/ije/dyz012
  • Peer Reviewed
• [Journal Article] Respiratory resistance among adults in a population-based cohort study in Northern Japan. (2019)
  • Author(s): Miura E, Tsuchiya N, Igarashi Y, Arakawa R, Nikkuni E, Tamai T, Tabata M, Ohkouchi S, Irokawa T, Ogawa H, Takai-Igarashi T, Suzuki Y, Kuriyama S, Tamiya G, Hozawa A, Yamamoto M, Kurosawa H.
  • Journal Title: Respiratory Investigation Volume: 印刷中 Issue: 3 Pages: 30226-0
  • DOI: 10.1016/j.resinv.2018.12.008
  • Peer Reviewed
• [Journal Article] Growth impairment in individuals with citrin deficiency (2019)
  • Author(s): Numakura Chikahiko、Tamiya Gen、Ueki Masao、Okada Tomoo、Maisawa Shun-ichi、Kojima-Ishii Kanako、Murakami Jun、Horikawa Reiko、Tokuhara Daisuke、Ito Koichi、Adachi Masanori、Abiko Takahiro、Mitsui Tetsuo、Hayasaka Kiyoshi
  • Journal Title: Journal of Inherited Metabolic Disease Volume: 42 Issue: 3 Pages: 501-508
  • DOI: 10.1002/jimd.12051
  • Peer Reviewed
• [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: 139-158
  • DOI: 10.1093/jb/mvy096
  • NAID: 40021809939
  • Peer Reviewed / Open Access
• [Journal Article] Potential identification of vitamin B6 responsiveness in autism spectrum disorder utilizing phenotype variables and machine learning methods (2018)
  • Author(s): Obara Taku、Ishikuro Mami、Kuriyama Shinichi、et al.
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 14840-14840
  • DOI: 10.1038/s41598-018-33110-w
  • URL: https://pure.teikyo.jp/en/publications/4d831045-f800-4e48-ace3-123ac9447869
  • Peer Reviewed / Open Access
• [Journal Article] Regional genetic differences among Japanese populations and performance of genotype imputation using whole-genome reference panel of the Tohoku Medical Megabank Project (2018)
  • Author(s): Yasuda Jun、et al.,
  • Journal Title: BMC Genomics Volume: 19 Issue: 1 Pages: 551-551
  • DOI: 10.1186/s12864-018-4942-0
  • Peer Reviewed / Open Access
• [Journal Article] Ethylene-gibberellin signaling underlies adaptation of rice to periodic flooding (2018)
  • Author(s): T Kuroha, K Nagai, R Gamuyao, D R Wang, T Furuta, M Nakamori, T Kitaoka, K Adachi, A Minami, Y Mori, K Mashiguchi, Y Seto, S Yamaguchi, M Kojima, H Sakakibara, J Wu, K Ebana, N Mitsuda, M Ohme-Takagi, S Yanagisawa, M Yamasaki, R Yokoyama, K Nishitani, T Mochizuki, G Tamiya, S R McCouch, and M Ashikari
  • Journal Title: Science Volume: 361 Issue: 6398 Pages: 181-186
  • DOI: 10.1126/science.aat1577
  • NAID: 120006529624
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Female Japanese quail visually differentiate testosterone-dependent male attractiveness for mating preferences (2018)
  • Author(s): Hiyama Gen、Mizushima Shusei、Matsuzaki Mei、Tobari Yasuko、Choi Jae-Hoon、Ono Takashi、Tsudzuki Masaoki、Makino Satoshi、Tamiya Gen、Tsukahara Naoki、Sugita Shoei、Sasanami Tomohiro
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 10012-10012
  • DOI: 10.1038/s41598-018-28368-z
  • 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
  • URL: https://localhost/en/publications/6383ce37-5ea4-4f7e-8493-1d86eac8314c
  • Peer Reviewed / Open Access
• [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
  • URL: https://pure.teikyo.jp/en/publications/68f9baf0-ba55-4278-8354-a10148b91802
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c. (2017)
  • Author(s): Hachiya T, Komaki S, Hasegawa Y, Ohmomo H, Tanno K, Hozawa A, Tamiya G, Yamamoto M, Ogasawara K, Nakamura M, Hitomi J, Ishigaki Y, Sasaki M, Shimizu A.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 16147-16147
  • DOI: 10.1038/s41598-017-16493-0
  • Peer Reviewed / Open Access
• [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] Detecting genetic association through shortest paths in a bidirected graph (2017)
  • Author(s): Ueki M, Kawasaki Y, Tamiya G
  • Journal Title: Genetic Epidemiology Volume: 未定 Issue: 6 Pages: 481-497
  • DOI: 10.1002/gepi.22051
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] AI創薬に向けた複雑な疾患の遺伝統計学モデル (2017)
  • Author(s): 高山 順, 田宮 元
  • Journal Title: CICSJ Bulletin Volume: 35 Issue: 2 Pages: 158
  • DOI: 10.11546/cicsj.35.158
  • NAID: 130005866034
  • ISSN: 0913-3747, 1347-2283
  • Peer Reviewed / Open Access
• [Journal Article] Detecting genetic association through shortest paths in a bi-directed graph. (2017)
  • Author(s): Ueki M, Kawasaki Y, Tamiya G.
  • Journal Title: Genet Epidemiol. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [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] Smooth-threshold multivariate genetic prediction with unbiased model selection (2016)
  • Author(s): Ueki M, Tamiya G
  • Journal Title: Genetic Epidemiology Volume: 40 Issue: 3 Pages: 233-243
  • DOI: 10.1002/gepi.21958
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ゲノムコホートのビッグデータ解析 (2016)
  • Author(s): 田宮元
  • Journal Title: 医学のあゆみ Volume: 259 Pages: 745-748
• [Presentation] 人工知能・機械学習手法による大規模ゲノムコホート解析 (2019)
  • Author(s): 田宮 元
  • Organizer: 第1回日本メディカルAI学会学術集会
  • Invited
• [Presentation] RNF213の遺伝統計解析 (2018)
  • Author(s): 田宮 元
  • Organizer: 日本脳神経外科学会 第77回学術総会
  • Invited
• [Presentation] 全ゲノム配列情報を用いた疾患発症予測に向けて (2018)
  • Author(s): 植木 優夫
  • Organizer: 科研費研究集会「予測モデリングとその周辺-機械学習・統計科学・情報理論からのアプローチ-」
• [Presentation] ジャポニカアレイの遺伝統計解析 (2018)
  • Author(s): 田宮 元
  • Organizer: 第3回ジャポニカアレイ研究会
  • Invited
• [Presentation] ゲノムデータ解析の理論と実践 (2018)
  • Author(s): 植木 優夫
  • Organizer: リスク解析戦略研究センターシンポジウム
  • Invited
• [Presentation] 人工知能技術によるゲノムコホート研究 (2018)
  • Author(s): 田宮 元
  • Organizer: 第225回日本小児科学会宮城地方会
  • Invited
• [Presentation] Detecting genetic association through shortest paths in a bidirected graph (2018)
  • Author(s): M. Ueki, Y. Kawasaki, G. Tamiya
  • Organizer: International Workshop at Waseda University 2018 (IWAWU2018)
  • Int'l Joint Research / Invited
• [Presentation] 双方向グラフ上の最短経路を利用した遺伝関連解析 (2018)
  • Author(s): 植木優夫、川崎能典、田宮 元
  • Organizer: 科研費研究集会・「生命・自然科学における複雑現象解明のための統計的アプローチ」
• [Presentation] ゲノムコホートの遺伝統計学 (2017)
  • Author(s): 田宮元
  • Organizer: 科研費（基盤S）シンポジウム ＆ 統数研生物統計ネットワークシンポジウム（第8回）
  • Place of Presentation: アクロス福岡（福岡県・福岡市）
  • Year and Date: 2017-03-27
  • Invited
• [Presentation] Rapid and accurate genetic predictive modeling for large-scale genetic study. (2017)
  • Author(s): Ueki M.
  • Organizer: ISI-ISM-ISSAS Joint Conference
  • Place of Presentation: Delhi (India)
  • Year and Date: 2017-02-19
  • Int'l Joint Research
• [Presentation] Rapid and accurate genetic predictive modelling for large-scale genetic study (2017)
  • Author(s): Masao Ueki
  • Organizer: IASSL 3rd INTERNATIONAL CONFERENCE
  • Int'l Joint Research / Invited
• [Presentation] 東北メディカル・メガバンク機構の大規模ゲノムデータの紹介 (2017)
  • Author(s): 田宮 元
  • Organizer: 2017年度生命科学系学会合同年次大会
  • Invited
• [Presentation] Detecting genetic association through shortest paths in a bidirected graph (2017)
  • Author(s): Masao Ueki
  • Organizer: ISI-ISM-ISSAS Joint Conference
  • Int'l Joint Research
• [Presentation] Machine Learning / Artificial Intelligence Based Methods for Genomic Cohort (2017)
  • Author(s): Gen Tamiya
  • Organizer: 2nd Karolinska-Tohoku Joint Symposium on Medical Sciences
  • Int'l Joint Research / Invited
• [Presentation] ジャポニカアレイを用いた東北メディカル・メガバンク機構大規模ゲノムコホートの解析について (2017)
  • Author(s): 田宮 元
  • Organizer: 第2回ジャポニカアレイ研究会
  • Invited
• [Presentation] Genetic Epidemiological Studies of the ToMMo Genomic Cohorts (2017)
  • Author(s): Gen Tamiya
  • Organizer: 第21回国際疫学会総会
  • Int'l Joint Research / Invited
• [Presentation] Detecting genetic association through shortest paths in a bidirected graph (2017)
  • Author(s): M. Ueki, Y. Kawasaki, G. Tamiya
  • Organizer: IFCS2017
  • Int'l Joint Research / Invited
• [Presentation] ゲノム医療におけるリスク予測へ向けて (2017)
  • Author(s): 田宮 元
  • Organizer: NGS現場の会第五回研究会
  • Invited
• [Presentation] Smooth-threshold multivariate genetic prediction with unbiased model selection. (2016)
  • Author(s): Ueki M, Tamiya G.
  • Organizer: Annual Meeting of the American Society for Human Genetics
  • Place of Presentation: Vancouver (Canada)
  • Year and Date: 2016-10-18
  • Int'l Joint Research
• [Presentation] Smooth-threshold multivariate genetic prediction with unbiased model selection (2016)
  • Author(s): Ueki M, Tamiya G.
  • Organizer: 2016 International Conference for JSCS 30th Anniversary in Seattle
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2016-10-16
  • Int'l Joint Research
• [Presentation] 大規模ゲノムコホートの遺伝統計学 (2016)
  • Author(s): 田宮元
  • Organizer: 第5回生命医薬情報学連合大会（IIBMP 2016）
  • Place of Presentation: 東京国際交流館プラザ平成（東京都・江東区）
• [Book] ゲノムデータ解析 (2016)
  • Author(s): 冨田誠, 植木優夫
  • Total Pages: 116
  • Publisher: 共立出版
• [Remarks] リスク統計解析室
  • URL: http://www.genetix-h.com/~AMERI/
• [Remarks] リスク統計解析室
  • URL: http://www.genetix-h.com/~AMERI/index.html