アブイニシオ代謝経路再構築へ向けた反応ネットワーク予測

• Project Area: Biosynthetic machinery: Deciphering and regulating the system for bioactive metabolite diversification
• Project/Area Number: 25108714
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: 小寺 正明 東京工業大学, 生命理工学研究科, 講師 (90643669)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 代謝経路 / 代謝ネットワーク / 化合物 / 酵素反応 / 構造比較 / バイオインフォマティクス / 生合成 / 機械学習 / ケモインフォマティクス

Outline of Annual Research Achievements

代謝経路解析は代謝工学だけでなく、計画的な創薬研究にも重要である。しかし、薬理活性のある天然物やその他の代謝物の数に比べて、その生合成・生分解経路が明らかになっているものの数は極めて少ない。そこで本研究では、メタボローム（網羅的代謝解析）スケールの多数の化合物に対し、その化学構造データのみから新規代謝経路を推定する手法の開発を進めている。既知の代謝経路中の反応パターンを用いた解析から、代謝経路中の酵素反応はただ無秩序に並んでいるのではなく、保存された連続反応モジュールが存在していることが知られ、それらの中にはゲノム中の遺伝子クラスター構造と対応関係にあるものもある。このような知見から我々は、代謝経路を構成する反応のひとつひとつを単独で取り扱うだけでなく、連続反応を考慮に入れた研究を行なった。本研究では先行研究の「酵素反応らしさ」をより一般化した「kステップ反応らしさ」を扱い、２つの化合物が与えられたとき、その出発物質と最終産物が何ステップの反応で結ばれるか、そしてその中間体構造は何かを推定する問題を解いた。様々な化合物表現法と予測法による予測精度を比較した結果、KCF-Sベクトルを用いたL1SVMが最も良好であることが分かった。以上の結果は、生命情報学分野で世界最大の国際学会であるISMB 2014に採択され口頭発表した上、同分野での最有力誌であるBioinformatics誌に掲載された。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] PIERO ontology for analysis of biochemical transformations: Effective implementation of reaction information in the IUBMB Enzyme List (2014)
  • Author(s): Masaaki Kotera, Yosuke Nishimura, Zen-ichi Nakagawa, Ai Muto, Yuki Moriya, Shinobu Okamoto, Shuichi Kawashima, Toshiaki Katayama, Toshiaki Tokimatsu, Minoru Kanehisa, and Susumu Goto
  • Journal Title: Journal of Bioinformatics and Computational Biology Volume: 21 Issue: 06 Pages: 1-17
  • DOI: 10.1142/s0219720014420013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] WURCS: the Web3 unique representation of carbohydrate structures. (2014)
  • Author(s): Tanaka K, Aoki-Kinoshita KF, Kotera M, Sawaki H, Tsuchiya S, Fujita N, Shikanai T, Kato M, Kawano S, Yamada I, Narimatsu H.
  • Journal Title: J Chem Inf Model. Volume: 54(6) Issue: 6 Pages: 1558-66
  • DOI: 10.1021/ci400571e
  • Peer Reviewed / Open Access
• [Journal Article] DINIES: drug-target interaction network inference engine based on supervised analysis (2014)
  • Author(s): Yoshihiro Yamanishi, Masaaki Kotera, Yuki Moriya, Ryusuke Sawada, Minoru Kanehisa, Susumu Goto
  • Journal Title: Nucleic Acids Research Volume: 42 Issue: W1 Pages: W39-W45
  • DOI: 10.1093/nar/gku337
  • Peer Reviewed / Open Access
• [Journal Article] Metabolome-scale prediction of intermediate compounds in multi-step metabolic pathways with a recursive supervised approach (2014)
  • Author(s): Masaaki Kotera, Yasuo Tabei, Yoshihiro Yamanishi, Ai Muto, Yuki Moriya, Toshiaki Tokimatsu, Susumu Goto
  • Journal Title: Bioinformatics Volume: 30 Issue: 12 Pages: i165-i174
  • DOI: 10.1093/bioinformatics/btu265
  • NAID: 130005072035
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Predictive genomic and metabolomic analysis for the standardization of enzyme data (2014)
  • Author(s): Masaaki Kotera, Susumu Goto and Minoru Kanehisa
  • Journal Title: Perspectives in Science Volume: 1 Issue: 1-6 Pages: 24-32
  • DOI: 10.1016/j.pisc.2014.02.003
  • Open Access
• [Journal Article] Benchmarking a wide range of chemical descriptors for drug-target interaction prediction using a chemogenomic approach (2014)
  • Author(s): Ryusuke Sawada, Masaaki Kotera, and Yoshihiro Yamanishi
  • Journal Title: Molecular Informatics Volume: 33 Issue: 11-12 Pages: 719-731
  • DOI: 10.1002/minf.201400066
  • Peer Reviewed
• [Journal Article] KCF-S: KEGG Chemical Function and Substructure for improved interpretability and prediction in chemical bioinformatics (2013)
  • Author(s): Masaaki Kotera, Yasuo Tabei, Yoshihiro Yamanishi, Yuki Moriya, Toshiaki Tokimatsu, Minoru Kanehisa and Susumu Goto.
  • Journal Title: BMC Systems Biology Volume: 7 Issue: S6
  • DOI: 10.1186/1752-0509-7-s6-s2
  • Peer Reviewed
• [Journal Article] Supervised de novo reconstruction of metabolic pathways from metabolome-scale compound sets (2013)
  • Author(s): Masaaki Kotera, Yasuo Tabei, Yoshihiro Yamanishi, Toshiaki Tokimatsu and Susumu Goto.
  • Journal Title: Bioinformatics Volume: 29
  • Peer Reviewed
• [Journal Article] 代謝反応予測のケミカルバイオインフォマティクス (2013)
  • Author(s): 小寺正明
  • Journal Title: 日本化学会情報化学部会誌 Volume: 31 Pages: 30-33
  • NAID: 130003362387
• [Presentation] PIERO ontology for analysis of biochemical transformations: Effective implementation of reaction information in the IUBMB Enzyme List (2014)
  • Author(s): Masaaki Kotera
  • Organizer: GIW / ISCB-Asia 2014
  • Place of Presentation: 等強国際交流館（東京・お台場）
  • Year and Date: 2014-12-15 – 2014-12-17
  • Invited
• [Presentation] Metabolome-scale prediction of intermediate compounds in multi-step metabolic pathways with a recursive supervised approach (2014)
  • Author(s): Masaaki Kotera
  • Organizer: 生命医薬情報学連合大会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2014-10-02 – 2014-10-04
  • Invited
• [Presentation] Metabolome-scale prediction of intermediate compounds in multi-step metabolic pathways with a recursive supervised approach (2014)
  • Author(s): Masaaki Kotera
  • Organizer: ISMB 2014
  • Place of Presentation: ボストン
  • Year and Date: 2014-07-11 – 2014-07-15
  • Invited
• [Presentation] KCF-S: KEGG Chemical Function and Substructure for improved interpretability and prediction in chemical bioinformatics (2013)
  • Author(s): Masaaki Kotera
  • Organizer: The 24th International Conference on Genome Informatics(GIW2013)
  • Place of Presentation: Singapore
• [Presentation] Metabolome-scale prediction of enzyme reaction network based on chemical structures (2013)
  • Author(s): Masaaki Kotera
  • Organizer: The 8th Metabolome Symposium
  • Place of Presentation: Fukuoka
• [Presentation] Supervised learning of enzymatic reaction likeness for de novo reconstruction of metabolic pathways (2013)
  • Author(s): Masaaki Kotera
  • Organizer: 13th Annual International Workshop on Bioinformatics and Systems Biology
  • Place of Presentation: Kyoto
• [Presentation] Supervised de novo reconstruction of metabolic pathways from metabolome-scale compound sets (2013)
  • Author(s): Masaaki Kotera
  • Organizer: ISMB ECCB 2013
  • Place of Presentation: Berlin, Germany