Development of statistical evaluation method for artificial intelligence and deep learning for personalized medicine

• Project/Area Number: 19H01806
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 12040:Applied mathematics and statistics-related
• Research Institution: Teikyo University
• Principal Investigator: Matsuura Masaaki 帝京大学, 公私立大学の部局等, 教授 (40173794)
• Co-Investigator(Kenkyū-buntansha): 生亀 清貴 日本大学, 経済学部, 准教授 (30711593) ; 安藤 宗司 東京理科大学, 工学部情報工学科, 助教 (40803226) ; 牛嶋 大 公益財団法人がん研究会, 有明病院 臨床研究・開発センター, 研究員 (60328565) ; 小森 理 成蹊大学, 理工学部, 准教授 (60586379) ; 松井 茂之 名古屋大学, 医学系研究科, 教授 (80305854) ; 顧 艶紅 大阪医科薬科大学, 医学部, 講師 (30470595) ; 江口 真透 統計数理研究所, 数理・推論研究系, 教授 (10168776)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 統計 / 個別化医療 / 人口知能 / 深層学習 / データ解析 / データサイエンス / 疫学 / 統計学 / 人工知能

Outline of Research at the Start

最近、特許出願した不均一性抽出アルゴリズムの高精度化と再評価を行なう。また、深層学習の各層特徴抽出結果に対する各変数による統計学的性能評価法の検討を行い、さらに教師ありデータに対する計算機集約的統計手法を用いたデータ活用法の開発を試みる。これら手法の応用として、乳がん患者公開データに対する集団の不均一性を考慮したバイオマーカー抽出を行う

Outline of Final Research Achievements

In this research, data analysis using artificial intelligence and deep learning, which has recently begun to be used in medicine, is becoming widespread in order to realize and accelerate personalized medicine. However, there are criticisms that the analysis content is black box-like as to how the analysis results were derived. Therefore, we conducted research to add an evaluation from a statistical point of view regarding "contribution of each feature of deep learning", and in particular, conducted research on specific problems using various actual data, and based on these experiences. We proposed a simple new method.

Academic Significance and Societal Importance of the Research Achievements

これまでの人工知能・深層学習を用いたデータ解析には、主に画像解析の画素をデータとして取り扱う分野の発展が著しいが、医学的臨床情報を用いる分野では各種臨床検査値やオミックスデータの情報を変数として取り扱う分野の発展が望まれてきた。しかし、後者の場合の解析結果は、最終結果のみが出力され、医学で重要な解析で使用した各種因子や説明変数の寄与度が明らかでない点が問題であった。本研究では、実データを用いて研究を推進した。

Research Products

• [Journal Article] A prediction model for early systemic recurrence in breast cancer using a molecular diagnostic analysis of sentinel lymph nodes: A large-scale, multicenter cohort study. (2022)
  • Author(s): Osako, T., Matsuura, M., Yotsumoto, D., Takayama, S., Kaneko, K., Takahashi, M., Shimazu, K., Yoshidome, K., Kuraoka, K., Itakura, M., Tani, M., Ishikawa, T., Ohi, Y., Kinoshita, T., Sato, N., Tsujimoto, M., Nakamura, S., Tsuda, H., Noguchi, S., Akiyama, F.
  • Journal Title: Cancer Volume: 128(10): Issue: 10 Pages: 1913-1920
  • DOI: 10.1002/cncr.34144
  • Peer Reviewed / Open Access
• [Journal Article] Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs. (2022)
  • Author(s): Hirai T, Suzuki A, Yamori T, Matsuura M.
  • Journal Title: Invest New Drugs Volume: 40(1) Issue: 1 Pages: 142-150
  • DOI: 10.1007/s10637-021-01165-8
  • Peer Reviewed
• [Journal Article] Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects. (2021)
  • Author(s): Gu YH, Zhang Q, Guo J, Wang F, Bao Y, Qiu Z, Zheng P, Ushijima M, Matsuura M, Xie X, Zhang T.
  • Journal Title: J Trace Elem Med Biol. Volume: 68, 126814 Pages: 1-9
  • DOI: 10.1016/j.jtemb.2021.126814
  • Peer Reviewed / Open Access
• [Journal Article] Situation analyses of caregivers' knowledge on infant liquid formula in Japan: a cross-sectional questionnaire-based study. (2021)
  • Author(s): Mizutani S, Takahashi K, Matsuura M.
  • Journal Title: Pediatr Int. Volume: 64(1):e14868 Issue: 1 Pages: 1-7
  • DOI: 10.1111/ped.14868
  • Peer Reviewed / Open Access
• [Journal Article] Lamellarin 14, a derivative of marine alkaloids, inhibits the T790M/C797S mutant epidermal growth factor receptor (2021)
  • Author(s): Nishiya Naoyuki、Oku Yusuke、Ishikawa Chie、Fukuda Tsutomu、Dan Shingo、Mashima Tetsuo、Ushijima Masaru、Furukawa Yoko、Sasaki Yuka、Otsu Keishi、Sakyo Tomoko、Abe Masanori、Yonezawa Honami、Ishibashi Fumito、Matsuura Masaaki、Tomida Akihiro、Seimiya Hiroyuki、Yamori Takao、Iwao Masatomo、Uehara Yoshimasa
  • Journal Title: Cancer Science Volume: － Issue: 5 Pages: 1963-1974
  • DOI: 10.1111/cas.14839
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenicity assessment of variants for breast cancer susceptibility genes based on BRCAness of tumor sample (2021)
  • Author(s): Yoshida R, Hagio T, Kaneyasu T, Gotoh O, Osako T, Tanaka N, Amino S, Yaguchi N, Nakashima E, Kitagawa D, Ueno T, Ohno S, Nakajima T, Nakamura S, Miki Y, Hirota T, Takahashi S, Matsuura M, Noda T, Mori S.
  • Journal Title: Cancer Sci. Volume: 112(3) Issue: 3 Pages: 1310-1319
  • DOI: 10.1111/cas.14803
  • Peer Reviewed / Open Access
• [Journal Article] The preoperative risk factors of postoperative self-extubation in elderly patients. (2019)
  • Author(s): Konishi Y, Nakata Y, Nemoto A, Ushijima M, Matsuura M.
  • Journal Title: Int J Risk Saf Med. Volume: 30(1) Issue: 1 Pages: 9-18
  • DOI: 10.3233/jrs-180011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Prostaglandin E-major urinary metabolite as a noninvasive surrogate marker for infantile necrotizing enterocolitis. (2019)
  • Author(s): Konishi KI, Yoshida M, Nakao A, Tsuchiya K, Tsurisawa C, Ichiki K, Takeda T, Hisaeda Y, Hirota A, Amagata S, Odashima T, Yokomori K, Ishida K, Matsuura M, Ito S, Fujiwara M, Nakahara S.
  • Journal Title: J Pediatr Surg. Volume: 54 Issue: 8 Pages: 1584-1589
  • DOI: 10.1016/j.jpedsurg.2018.08.044
  • Peer Reviewed
• [Presentation] 神経管閉鎖障害児の胎盤における甲状腺ホルモン脱ヨード酵素の一塩基多型に関する症例対照研究 (2022)
  • Author(s): 顧 艶紅、松浦正明、鄭 萍、牛嶋 大、張 霆
  • Organizer: 第32回日本疫学会学術総会、オンライン
• [Presentation] Evaluation of prediction performance for Cox proportional hazards model (2020)
  • Author(s): Masaaki Matsuura, Tasuku Yoshida and Shuji Ando
  • Organizer: International Biometric Society 2020
  • Int'l Joint Research
• [Presentation] Evaluation of prediction performance for Cox proportional hazards model (2019)
  • Author(s): Masaaki Matsuura, Tasuku Yoshida and Shuji Ando
  • Organizer: International Biometric Society 2020
  • Int'l Joint Research
• [Book] 「オミックス解析：表現型・薬物活性とリンクする分子経路の探索.」 マウス・ラット モデル作製・解析．プロフェッショナル 先端モデル動物支援プラットフォーム（AdAMS）／編 (2021)
  • Author(s): 室井誠，馬島哲夫，牛嶋大，松浦正明
  • Total Pages: 11
  • Publisher: 羊土社
  • ISBN: 9784758121125