Attempts in unifying biological molecular data via graph methods

• Project/Area Number: 25280109
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: Shirai Tsuyoshi 長浜バイオ大学, バイオサイエンス学部, 教授 (00262890)
• Co-Investigator(Kenkyū-buntansha): OOYAMA TAKUJI 山梨大学, 医学工学総合研究部, 准教授 (60423133) ; MAYANAGI KOUTA 九州大学, 生体防御医学研究所, 助教 (50418571)
• Co-Investigator(Renkei-kenkyūsha): ISHINO YOSHIZUMI 九州大学, 農学研究科, 教授 (30346837)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 生体生命情報学 / 分子機械 / 高分子構造・物性 / アルゴリズム / 生体超分子構造 / 高分子構造・物性 アルゴリズム

Outline of Final Research Achievements

The biological data are hierarchical, and graph is one of the best data structures for presenting and unifying various biological data from molecules to phylogeny. In this study, multidisciplinary approach was taken to device the methods in comparing biological graphs. The graph-matching method for small molecules had successfully related structures and functions of naturally occurring drugs. The method for comparing phylogenetic trees was used to identify orthologous gene clusters in complex trees. The graph-based supramolecular modeling method had generated 3,197 human protein complex models, and the models revealed disease-related SNVs on the molecular interface for more than 10 disease. The model for EndoMS-PCNA-DNA complex, which specifically cleave mismatched DNA, was verified experimentally by single-particle EM method, and the graph-generated model was shown to be consistent with the experimental structure. The results indicated the usefulness of the graph-based methods.

Research Products

• [Journal Article] Identification of a mismatch-specific endonuclease in hyperthermophilic Archaea. (2016)
  • Author(s): Ishino S, Nishi Y, Oda S, Uemori T, Sagara T, Takatsu N, Yamagami T, Shirai T, Ishino Y.
  • Journal Title: Nucleic Acid Res. Volume: 124 Pages: 2977-2086
  • DOI: 10.1093/nar/gkw153
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel AVPR2 mutation causing partial nephrogenic diabetes insipidus in a Japanese family (2016)
  • Author(s): Yamashita S, Hata A, Usui T, Oda H, Hijikata A, Shirai T, Kaneko N, Hata D
  • Journal Title: J Pediatr Endocrinol Metab Volume: 5 Pages: 591-596
  • DOI: 10.1515/jpem-2015-0323
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deciphering Supramolecular Structures with Protein-Protein Interaction Network Modeling (2015)
  • Author(s): Toshiyuki Tsuji, Takao Yoda, and Tsuyoshi Shirai
  • Journal Title: Scientific Reports Volume: 5 Pages: 16341-16341
  • DOI: 10.1038/srep16341
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The influence of PRNP polymorphisms on human prion disease susceptibility: an update (2015)
  • Author(s): Kobayashi A, Teruya K, Matsuura Y, Shirai T, Nakamura Y, Yamada M, Mizusawa H, Mohri S, Kitamoto T.
  • Journal Title: Acta Neuropathol. Volume: 130 Pages: 159-170
  • DOI: 10.1007/s00401-015-1447-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 超分子モデリングによる創薬支援 (2015)
  • Author(s): 土方敦司、辻 敏之、白井 剛
  • Journal Title: SAR News Volume: 28 Pages: 1-7
• [Journal Article] Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities (2014)
  • Author(s): Ohtana Y,Abdullah AA, Amin MA,Huang M,Ono N, Sato T,Sugiura T,Horai H,Nakamura Y,Morita AH, Lange KW,Kibinge NK, Katsuragi T,Shirai T,Kanaya S
  • Journal Title: Mol. Inform. Volume: 33 Pages: 790-801
  • DOI: 10.1002/minf.201400123
  • NAID: 130005146305
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Aicardi-Goutières syndrome is caused by IFIH1 mutations. (2014)
  • Author(s): Oda, H., Nakagawa, K., Abe, J., Awaya, T., Funabiki, M., Hijikata, A., Nishikomori, R., Funatsuka, M., Ohshima, Y., Sugawara, Y., Yasumi, T., Kato, H., Shirai, T., Ohara, O., Fujita, T., Heike, T.
  • Journal Title: Am. J. Hum. Genet. Volume: 95 Pages: 121-125
  • DOI: 10.1016/j.ajhg.2014.06.007
  • NAID: 120005460706
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Evaluating Prion Models Based on Comprehensive Mutation Data of Mouse PrP. (2014)
  • Author(s): Shirai T, Saito M, Kobayashi A, Asano M, Hizume M, Ikeda S, Teruya K, Morita M, Kitamoto T.
  • Journal Title: Structure Volume: 22 Pages: 560-571
  • DOI: 10.1016/j.str.2013.12.019
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Crystallization and preliminary X-ray diffraction analysis of domain chimeric L-(2S, 3S)-butanediol dehydrogenase (2014)
  • Author(s): Shimegi T, Oyama T, Ohtsuki T, Kurisu G, Kusunoki M, Ui S
  • Journal Title: Acta Cryst F Volume: 70 Pages: 461-463
  • DOI: 10.1107/s2053230x13032755
  • Peer Reviewed
• [Journal Article] Structure of the entire stalk region of the dynein motor domain (2014)
  • Author(s): Yosuke Nishikawa, Takuji Oyama, Narutoshi Kamiya, Takahide Kon, Yoko Y. Toyoshima, Haruki Nakamura, Genji Kurisu
  • Journal Title: J. Mol. Biol. Volume: 426 Pages: 3232-3245
  • DOI: 10.1016/j.jmb.2014.06.023
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Revealing the intracellular ultrastructure of filopodia with cryo-electron tomography. (2014)
  • Author(s): Shinji Aramaki, Kouta Mayanagi, Kazuhiro Aoyama and Takuo Yasunaga
  • Journal Title: Microscopy Volume: 63 Pages: 133-134
  • DOI: 10.1093/jmicro/dfu071
  • Peer Reviewed
• [Journal Article] The centromeric nucleosome-like CENP-T-W-S-X complex induces positive supercoils into DNA. (2014)
  • Author(s): Kozo Takeuchi, Tatsuya Nishino, Kouta Mayanagi, Naoki Horikoshi, Akihisa Osakabe, Hiroaki Tachiwana, Tetsuya Hori, Hitoshi Kurumizaka and Tatsuo Fukagawa.
  • Journal Title: Nucleic Acid Research Volume: 42 Pages: 16441655-16441655
  • DOI: 10.1093/nar/gkt1124
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] データベース解析によるタンパク質リガンドの多様性 (2013)
  • Author(s): 白井 剛
  • Journal Title: 生化学 Volume: 85 Pages: 671-687
  • NAID: 10031195378
  • Peer Reviewed
• [Presentation] Development of a protein-protein docking method based on matching of vector-presented amino acid residues (2015)
  • Author(s): Hijikata A, Shionyu M, Shirai T
  • Organizer: 生命医薬情報学連合大会
  • Place of Presentation: 京都府宇治市
  • Year and Date: 2015-10-29
• [Presentation] タンパク質超分子モデリングによる疾患関連変異の解析 (2015)
  • Author(s): 辻 敏之, 依田隆夫, 白井 剛
  • Organizer: 生命医薬情報学連合大会2015年大会
  • Place of Presentation: 京都府宇治市
  • Year and Date: 2015-10-29
  • Invited
• [Presentation] Analyzing disease-related amino acid variants with protein supramolecule modeling (2015)
  • Author(s): 辻 敏之, 依田隆夫, 白井 剛
  • Organizer: 生命医薬情報学連合大会2015年大会
  • Place of Presentation: 京都府宇治市
  • Year and Date: 2015-10-29
• [Presentation] A statistical amino acid pair potential to re-rank protein-protein docking poses predicted by a vector match algorithm (2015)
  • Author(s): Hijikata A, Shionyu M, Shirai T
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-09-13
• [Presentation] Structure prediction and analyses of endonuclease NucS from Thermococcus kodakaraensis (2015)
  • Author(s): Nakae S, Hijikata A, Tsuji T, Yonezawa K, Kouyama K, Mayanagi K, Ishino S, Ishino Y, Shirai T
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-09-13
• [Presentation] Relationship between protein-protein interaction interface predicted by complex modeling and disease-related amino acid variants (2015)
  • Author(s): 辻 敏之, 依田隆夫, 白井 剛
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 石川県金沢市
  • Year and Date: 2015-09-13
• [Presentation] マルチドメインタンパク質の構造予測サーバの構築 (2015)
  • Author(s): 塩生真史, 土方敦司, 白井 剛
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 2015-06-24
• [Presentation] Development of method for protein-protein interaction modeling using IntAct database (2015)
  • Author(s): 辻 敏之, 依田隆夫, 白井 剛
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 2015-06-24
  • Invited
• [Presentation] タンパク質相互作用データベースを利用した超分子モデリング法の開発 (2015)
  • Author(s): 辻 敏之, 依田隆夫, 白井 剛
  • Organizer: 第15回日本蛋白質科学会年会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 2015-06-24
• [Presentation] Supramolecular modeling pipeline for correlative structural analysis and rational drug-design (2014)
  • Author(s): 白井 剛
  • Organizer: 第53回日本生物物理学会年会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] イントロダクション:3D遺伝学のすすめ (2014)
  • Author(s): 白井 剛
  • Organizer: 第86回遺伝学会年会
  • Place of Presentation: 滋賀県
  • Year and Date: 2014-09-19
  • Invited
• [Presentation] Single particle analysis of molecular architecture of DNA replication fork complex and switching mechanism of replication factors (2014)
  • Author(s): Kouta Mayanagi, Shinichi Kiyonari, Hirokazu Nishida, Sonoko Ishino, Ryosuke Fujikane, Mihoko Saito, Daisuke Kohda, Yoshizumi Ishino, Tsuyoshi Shirai, Kosuke Morikawa
  • Organizer: 18th International Microscopy Congress
  • Place of Presentation: Prague Czech Republic
  • Year and Date: 2014-09-07 – 2014-09-12
• [Presentation] 超分子モデリングパイプラインの構築による相関構造解析•理論創薬支援 (2014)
  • Author(s): 白井 剛
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-25
  • Invited
• [Presentation] 超分子モデリングパイプラインの構築 (2014)
  • Author(s): 白井 剛
  • Organizer: 創薬等支援技術基盤プラットフォームテクニカルセミナー2014
  • Place of Presentation: 名古屋市
  • Year and Date: 2014-06-24
  • Invited
• [Presentation] Molecular architecture and switching mechanism of the replication fork complex (2014)
  • Author(s): Kouta Mayanagi, Shinichi Kiyonari, Hirokazu Nishida, Sonoko Ishino, Mihoko Saito, Daisuke Kohda, Yoshizumi Ishino, Tsuyoshi Shirai, Kosuke Morikawa
  • Organizer: Gordon Research Conference
  • Place of Presentation: Girona, Spain
  • Year and Date: 2014-06-22 – 2014-06-27
• [Presentation] Electron microscopic analysis of molecular architecture and switching mechanism of DNA replication fork complex (2013)
  • Author(s): Mayanagi K, Kiyonari S, Nishida H, Ishino S, Saito M, Kohda D, Ishino Y, Morikawa K
  • Organizer: ICSG2013-SLS
  • Place of Presentation: Sapporo, Hokkaidou
• [Presentation] Activation mechanism of the replicative helicase in the thermophilic archaeon, Thermoplasma acidophilum (2013)
  • Author(s): Ogino H, Ishino S, Mayanagi K, Oyama T, Shirai T, Morikawa K, Haugland GT, Birkeland NK, Kohda D, Ishino Y
  • Organizer: Thermophiles 2013
  • Place of Presentation: Regensburg, Germany
• [Presentation] 好熱性アーキアThermoplasma acidophilumにおける複製ヘリカーゼ活性化機構の分岐進化 (2013)
  • Author(s): 尾木野 弘実, 石野 園子, 真柳 浩太, 大山 拓次, 白井 剛, 森川 耿右, Haugland Gyri Teien, Birkeland Nils-Kare, 神田 大輔, 石野 良純
  • Organizer: 第１４回極限環境生物学会
  • Place of Presentation: 川崎, 神奈川県
• [Presentation] Divergently evolved activation mechanism of the replicative helicase in the thermophilic archaeon, Thermoplasma acidophilum (2013)
  • Author(s): Ogino H, Ishino S, Mayanagi K, Oyama T, Shirai T, Morikawa K, Haugland GT, Birkeland NK, Kohda D, Ishino Y
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸, 兵庫県
• [Book] バイオインフォマティクス入門 (2015)
  • Author(s): 日本バイオインフォマティクス学会編
  • Total Pages: 173
  • Publisher: 慶應義塾大学出版会
• [Book] Lectins: Methods and Protocols, Methods in Molecular Biology (2014)
  • Author(s): Ogawa T, Shirai T
  • Total Pages: 13
  • Publisher: Springer
• [Book] 生命のビッグデータ利用の最前線 (2014)
  • Author(s): 辻 敏之, 白井 剛
  • Total Pages: 7
  • Publisher: シーエムシー出版
• [Book] 生命のビッグデータ利用の最前線 (2014)
  • Author(s): 辻 敏之, 白井 剛
  • Total Pages: 7
  • Publisher: シーエムシー出版,
• [Book] Protein Engineering technology and application (2013)
  • Author(s): Ogawa T, Shirai T
  • Total Pages: 22
  • Publisher: InTech
• [Remarks] 土方特任講師が生命医薬情報学連合2015年大会 ポスター賞を受賞
  • URL: http://www.nagahama-i-bio.ac.jp/research/
• [Remarks] SIRD (Structure Interaction Relational Database)
  • URL: http://sird.nagahama-i-bio.ac.jp/sird/
• [Patent(Industrial Property Rights)] 耐熱性ミスマッチエンドヌクレアーゼの利用方法 (2015)
  • Inventor(s): 上森隆司, 石野良純, 2名, 白井 剛
  • Industrial Property Rights Holder: 上森隆司, 石野良純, 2名, 白井 剛
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-09-09
  • Overseas
• [Patent(Industrial Property Rights)] 耐熱性ミスマッチエンドヌクレアーゼの利用方法 (2014)
  • Inventor(s): 上森, 石野(園), 相良, 石野(良), 山上, 白井
  • Industrial Property Rights Holder: 上森, 石野(園), 相良, 石野(良), 山上, 白井
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-184934
  • Filing Date: 2014-09-11