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Bioinformatics and Systems Biology in Japan

　　

March 2005Toru YAO

Genomic Sciences Center/RIKENJBIRC/JBIC, CBRC/AIST

TOIN Yokohama Univ.

RIKEN's Research Locations

(Nagoya)

(Sendai)

▲RIKEN Wako Institute

▲RIKEN Harima Institute

▲RIKEN Kobe Institute

▲Bio-Mimetic 　　Control Research Center

▲RIKEN Yokohama Institute

▲RIKEN Tsukuba Institute

▲Photo Dynamics 　　 Research Center

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Floor Space:West Research Building 8,100 ㎡(August 2000)South Research Building 5,100 ㎡(April 2000)West NMR Complex 3,700 ㎡(April 2000)Central Research Building 10,800 ㎡(February 2003)Central NMR Complex 2,000 ㎡(October 2002)East Research Building 12,800 ㎡(March 2002)North Building 13,500 ㎡ (September 2003)Main Office Building 4,300 ㎡ (October 2001)------------------------------------------------------------------Total 60,300 ㎡

April 2004

(2000)

(2000)

(2000)

(2003)

(2003)

(2003)

(2001)

(2002)

Yokohama Institute

Abstract　 1. Japanese movements on Bioinformatics

Overall Japanese movements on Bioinformatics and Systems Biologywill be presented –Government and Private Sector

2. Some recent topics in Japan – Large Scale Mouse cDNA Annoutated DB (FANTOM) --Published--NextHuman cDNA Annoutated DB (H-InvDB) --Published--NextProtein 3000 Project --On going

　　　　 Genome Network Project --At start　　 Clinical Bioinformatics Research Initiative　

3. Partnership between Public and Private SectorSome examples will be presented including a Partnership with PrivateSector by RSGI (RIKEN Structural Genomics/Proteomics Initiative).

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Government・Reorganization of the Japanese government (Jan.2001)

1 Office and 12 MinistriesCabinet Office

Council for Science and Technology PolicyMECS + STA MEXT Ministry of Education and ScienceMITI METI Ministry of Economics and Industry

・The Basic Plan on Science and Technology for Five YearsR & D Budget will be 24 Tyen for 2001-2005)

( 17 Tyen for 1996-2000) doubledPriority1. Life Science/Biotechnology2. Information Technology3. Environment 3. Nanotechnology

Projects, Initiatives (Recent)

Brain Science Institute of RIKEN 1997-* Genomic Sciences Center of RIKEN 1998-

Rice Genome Project of MAF 1998-Genome Informatics Project 1998- DistributedRice Informatics Center (MAF) 1999-

Genome Information Science (2000-2004) Distributed

* Bioinformatics Group /GSC/RIKEN 2000-2004

* Biological Information Research Center (METI) 2000-2007* Computational Biology Research Center (METI) 2000-2007

Simulation of Biological Function (Keio-Kyoto-Osaka Univ.)* Genome Network Project (RIKEN-Academia-Industries)

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Basic Strategy for the Bioindustries 2,000 B Yen / 5 yearsUnder the Agreement by 4 Ministries (METI, MAFF, MHW and MEXT)

1. Infrastructure for the Promotion of New Businesses1) Genome Analysis2) Bio-Network3) Bioinformatics

2. Technology Development and New Business 1) Promotion of Industrialized R & D2) Funding for the Venture Businesses

3. Various Actions for Biotechnologies1) Research Centers for Advanced Research2) Technology Transfers of Academic Research3) Protection of Intellectual Properties

4. Consensus on the Ethical Problems by People

National Biotechnology Strategy Dec. 6, 2002www.jba.or.jp

1. R & D action plan 961) Doubling of Budget in 5 years2) Tripling of researchers 3) Fusion of Biotech with Nanotech, IT

2. Commercialize action plan 701) Systems Change e.g. Clinical Research 2) Deregulation3) Incentives e.g. Tax, Free zone

3. Public Acceptance action plan 341) Education2) Communication3) ELSI Budget4) Risk Management

Target in 2010 25 trillion yen market ( 1.4 TY in 2002)

1 million employees (30 thousand in 2002)

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GENOME The New Academic Program C for 2000-2004

1. Integrated Genome Research (Kohara)

Towards the understanding of the systems of life

2. Genome Medicine (Sugano)

Analysis of Human Diseases from Genes

3. Genome Biology (Ogasawara)

Understanding of the Cell Systems

4. Genome Informatics (Takagi)

The Next generation of the Bioinformatics

Next step will start from 2005--

“Human Genome Diversity”Dr. NakamuraSchool of Medicine, Univ. of Tokyo

“Disease Gene”Dr. HirohashiNational Cancer Research Center

“Bioinformatics”Dr. GojoboriNational Institute of Genetics

“Generation”Dr. NishikawaUniversity of Kyoto

“Rice Genome”Dr. KatsuraNational Institute of Agrobiological Sciences

Millennium ProjectMillennium Project

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Bioinformatics in the Millennium Project( Leader: T.Gojyobori )

1. Genome Information Science (T.Takagi)

2. Structural Informatics (Y.Kyogoku-passed away)3. Functional Informatics (N.Nomura)

4. Bioinformatics Technologies (Y.Akiyama)5. Knowledge-based Bioinformatics

and Bio-Computing (A.Konagaya)

6. SNPs Informatics Network (M.Kuroda)7. Gene Resource Data Base (Y.Kohara)

8. Integrated Bio-Systems Data Base (M.Kanehisa)9. Disease Data Base (T.Yoshida)

10. DNA Data Base – DDBJ (T.Gojyobori)

Genome・DNA sequence data（DDBJ）

Genome・DNA sequence data（DDBJ）

（Effect）

Database of Genetic Resources（NIG）

Database of Genetic Resources（NIG）

IMS-JST SNPs database（JST・IMS-UT）

IMS-JST SNPs database（JST・IMS-UT）

Disease Database（Natl Cancer Ctr ,etc）

Disease Database（Natl Cancer Ctr ,etc）KEGG（Kyoto Univ）KEGG（Kyoto Univ） Integrated Database

(JBIRC)

Integrated Database(JBIRC)

　　Grant-in-Aid for Scientific Research

(Special-C) by MEXT「Informatics」

StructuralAnd Functional Genomics (JBIRC)

Computational Biology

Research Center

IndustryIndustryEducationEducation MedicineMedicineScience

RIKENGenomic Sciences Center

Millennium Project

２

Development of bioinformatics-technology

Outline of Millennium Project -Bioinformatics-Coordinated by Prof.T.Gojyobori

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GenBankNCBI(USA)

Since 1982

EMBLEBI

(Europe)Since 1980

DDBJDDBJ

(Japan)Since 1986

Commitment to Commitment to International CollaborationInternational CollaborationUSTPO EPO

JPO

ーDNA Data Bank of Japanー （DDBJ）

70%10%

20%

Systems BiologyEmerging Field in the post genomic era

We should understand “Life as a system or an organization of

various systems”.

Computational network model –simulationExperimental Data and Knowledge

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from A.Konagaya

By A.Konagaya

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Systems Biology in Japan・Kanehisa--KEGG --Metabolic Pathway Database www.kegg.org

　 Bioinformatics Center (Apr. 2001) www.bic.kyoto-u.ac.jp

• Tomita--E-Cell --Simulation inside cells Red Blood cell etc.www.e-cell.org

Advanced Life Science Research Institute (May 2001) www.iab.keio.ac.jpMetabolic Eng., Microbiology, Genome Eng., Analitical Chemistry, Interactome and Bioinformatics

・　Kitano--SBML --System Biology Workbench　　www.sbml.org

Systems Biology Institute (July 2001)• RIKEN/GSC established a group on the genome network simulation

and will expand the activity in 2004. (Drs.Konagaya, Hayashizaki)

• Keio-Kyoto-Osaka Univ. started a project “Simulation of the Function of Cell, Tissue and Organ”.

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Systems Biology in Japan (2)

• MEXT Genome Research 2000---2004Understanding the Biological Systems

Microbes (Ogasawara）, Multi-Cellular (Kohara)PhotoSynthesis (Oomori), Gene Network (Kuhara)

• MAFF Rice Genome Simulator 2001---2005Databases and Simulation Methods for Rice14 teams for the Rice growth

• Other groupsOtake, Matsuda, Miyano, Takahashi, Tanaka, Okamoto,Kodama, Aihara

Industry and Academy

JBIC (Japan Biotechnology Informatics Consortium) 85 CompaniesInstruments, Software, Databases and Systems DevelopmentsInformation or Systems Services　　　　　　　　　　　 　www.jbic.or

CBI (Chemistry, Biology and Informatics) Society 50 Companies and Academics --Active monthly meetings

www.cbi.or.jp

JSBi (Society of Bioinformatics) Academic Society

JPS (Japan Protein Science) Society Academic Society--- PRC (Protein Research Communications)

SIGMBI (Molecular Biology Informatics) SIG from AI members

IPAB (Integrated Parallel Architecture for Biology) IT Industries

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International ConferenceRECOMB (Computational Biology) Mar. 2000 in TokyoICSB (Systems Biology) Nov. 2000 in TokyoICMG (Mouse Genome) Nov. 2000 in NaritaICSG (Structural Genomics) Nov. 2000 in YokohamaGEMINI (Human-Chimpanzee) Mar. 2001 in Tokyo

AGB (Advanced Genomics and Biology) Nov. 2001 in KyotoJune 2003 in Yokohama

GIW (Genome Informatics Workshop) Dec.2001 in TokyoDec.2002 in TokyoDec.2003 in Yokohama

AASBi 1st (Assoc. Asian Soc. for BI) Dec.2003 in Yokohama

Mouse FL cDNA FANTOM-1 Aug. 2000 in TsukubaFANTOM-2 Apr. 2002 in YokohamaFANTOM-3 Sep. 2004 in Wako

Human FL cDNA H-Invitational Jun.2002 in TokyoOct. 2003 in Tokyo

H-Inv-DE Sep. 2004 in TokyoSystems Biology of E.Coli Jun. 2003 in Tsuruoka

Projects –Large Scale

1. Mouse Full Length cDNA and Annotation

2. Integrated Database of Human Gene Annotation

3. Genome Network project

4. Protein 3000 project

５．Clinical Bioinformatics Research Initiative　　　　　　　　　　

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(1) Mouse Full Length cDNA Projecthttp://genome.gsc.riken.go.jp

To establish the Mouse Genome Encyclopedia

1995-----Planning, Technology Development 1998-----Project Start

Clones Ca.2,000,000 from more than 200 tissuesNon-Redundant Clones 128,000 EST PublishedFully Sequenced 21,000-->60,770

2001-----FANTOM 1 21.000Nature 409, 685-690 (2001)

2002-----FANTOM 2 60,770Nature 420, 520-562 (2002)

(Non Protein Coding RNAs) 16,0002003----FANTOM 3

Database is open to the world

Nature, volume 420, (December 5, 2002)Nature, 420, 520-562, 2002

Nature, 420, 563-573, 2002

Riken・MGSC collabora

In the history of science, mouse is the first organism whose transcriptome and genome were analyzed.

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Mouse Full length cDNNature Vol. 409, pp685-pp690,2001

Human genome draft Nature Vol. 409, pp860-pp921,2001

Riken-HGC collaboration

Full length cDNAs were the final proof to identify human genes and to predict total number of human genes

Genome sequence was used for genome mapping of Riken mouse full-length cDNA

267 tissues at different stages and at different organs

1,916,592 clones from normalized and subtracted libraries

This is equivalent to approximately14,400,000 clones from standard library

184,000 3‘-end clusters (159,789 new 3’-end sequences)

60,770 representative clones (FANTOM2 clones)were chosen for full sequencing

520,311 5‘-end sequences

FANTOM 2 activityFANTOM MeetingWork hard!

Work hard!

Work hard!

267 tissues at different stages and at different organs

1,916,592 clones from normalized and subtracted libraries

This is equivalent to approximately14,400,000 clones from standard library

184,000 3‘-end clusters (159,789 new 3’-end sequences)

60,770 representative clones (FANTOM2 clones)were chosen for full sequencing

520,311 5‘-end sequences

FANTOM 2 activity

Human Curation in FANTOM2 Meeting 25% were revised

33,994 unique FANTOM 2 sequences44,122 redundant public sequences

36830 unique sequences (RTPS; Representative Transcript and Protein Set)

3532 – 37690 additional Transcriptional Units identified by genome mapping of 1,485,901 3‘-end sequences and 604,677 5’-end sequences.

At least more than 43000 non-redundant unique TUs suported by

physical cDNA clones exist in mouse transcriptome.

Estimation: 60000-70000 TUs

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FANTOM Consortium:Y. Okazaki, M. Furuno, T. Kasukawa, J. Adachi, H. Bono, S. Kondo, I. Nikaido, N. Osato, R. Saito, H. Suzuki, I. Yamanaka, H. Kiyosawa, K. Yagi, Y. Tomaru, Y. Hasegawa, A. Nogami, C. Schönbach, T. Gojobori, R. Baldarelli, D.P. Hill, C. Bult, D.A. Hume, J. Quackenbush, L.M. Schriml, A. Kanapin, H. Matsuda, S. Batalov, K.W. Beisel, J.A. Blake, D. Bradt, V. Brusic, C. Chothia, L.E. Corbani, S. Cousins, E. Dalla, T.A. Dragani, C. F. Fletcher, A. Forrest, K.S. Frazer, T. Gaasterland, M. Gariboldi, C. Gissi, A. Godzik, J. Gough, S. Grimmond, S. Gustincich, N. Hirokawa, I.J. Jackson, E.D. Jarvis, A. Kanai, H. Kawaji, Y. Kawasawa, R. M. Kedzierski, B.L. King, A. Konagaya, I.V. Kurochkin, Y. Lee, B. Lenhard, P.A. Lyons, D.R. Maglott, L. Maltais, L. Marchionni, L. McKenzie, H. Miki, T. Nagashima, K. Numata, T. Okido, W.J. Pavan, G. Pertea, G. Pesole, N. Petrovsky, R. Pillai, J.U. Pontius, D. Qi, S. Ramachandran, T. Ravasi, J.C. Reed, D.J. Reed, J. Reid, B.Z. Ring, M. Ringwald, A. Sandelin, C. Schneider, C.A.M. Semple, M. Setou, K. Shimada, R. Sultana, Y. Takenaka, M.S. Taylor, R.D. Teasdale, M. Tomita, R. Verardo, L. Wagner, C. Wahlestedt, Y. Wang, Y. Watanabe, C. Wells, L.G. Wilming, A. Wynshaw-Boris, M. Yanagisawa, I. Yang, L. Yang, Z. Yuan M. Zavolan, Y. Zhu, A. Zimmer

RIKEN Genome Exploration Research Group Phase I:P. Carninci, N. Hayatsu, T. Hirozane-Kishikawa, H. Konno, M. Nakamura, N. Sakazume, K. Sato, T. Shiraki, K. Waki

RIKEN Genome Exploration Research Group Phase II:J. Kawai, K. Aizawa, T. Arakawa, S. Fukuda, A. Hara, W. Hashizume, K. Imotani, Y. Ishii, M. Itoh, I. Kagawa, A. Miyazaki, K. Sakai, D. Sasaki, K. Shibata, A. Shinagawa, A. Yasunishi, M. Yoshino

FANTOM Collaborator

Real International and Interdisciplinary Collaborationtoward the de-facto standard of gene encyclopedia

(2) Integrated Database of Human Gene Annotation --- H-InvDB

Annotation Jamboree were held in Tokyo in 2002 and 2003 more than 40,000 (60% from Japan)

　 H-Invitational DB was published in May 2004. T.Imanishi, T.Gojobori et al.

　　　 “Intgrative Annotation of 21,037 Human Genes 　validated by Full-Length cDNA Clones.”

　　　　　　　　　 PLoS Biology 2, 6, 1-20 (2004)

　　　 H-InvDB is open to the world www.h-invitational.jpwww.jbirc.aist.go.jp/index.jsp

H-Inv/DE was held in September in Tokyo

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Human Genome Papers

Whole Genome• International Human Genome Sequencing Consortium. Nature

409: 860-921 (2001)• Venter et al. Science 291: 1304-1351 (2001)

Chromosome Papers• chromosome 22 Dunham et al. Nature 402: 489-495 (1999)• chromosome 21 Hattori et al. Nature 405: 311-318 (2000)• chromosome 20 Deloukas et al. Nature 414: 865-871 (2001)• chromosome 14 Heilig et al. Nature 421: 601-607 (2003)• chromosome Y Skaletsky et al. Nature 423: 825-837 (2003)• chromosome 7 Hillier et al. Nature 424: 157-164 (2003)

“Human Full-Length cDNA Annotation Invitational”

(H-Invitational)August 25 - September 3, 2002

Co-organized by JBIRC and DDBJ/NIGAttended by more than 118 people from 40 organizations such as

JBIRC, DDBJ, NCBI, EBI, Sanger Centre,NCI-MGC, DOE, NIH, DKFZ, CNHGC(Shanghai), RIKEN, Tokyo U, MIPS, CNRS, MCW, TIGR, CBRC, Murdoch U, U Iowa, Karolinska Int., WashU, U Cincinnati,

Tokyo MD U, KRIBB, South African Bioinfor Inst, U College London, Reverse Proteomics Res. Inst., Kazusa DNA Inst, Weizmann Inst, Royal Inst. Tech. Sweden, Penn State U, Osaka U, Keio U, Kyushu U,

TIT, Ludwig Inst. Brazil, Kyoto U, German Can.Inst., and NIGSupported by

JBIC, METI, MEXT, NIH, and DOE

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H-Invitational

Organization entries

KIAA/Kazusa1 2,000NEDO/Kazusa2 256NEDO/UTIMS3 4,373NEDO/Helix4 8,157NEDO/New1+2+3+4 8,411DKFZ 5,596MGC/NCI 12,869CHGC 759

Total: 41,118

Six DNA Research Centersand DDBJ conducted a datafreeze on July 15, 2002.

A total of 41,118 cDNAs werecollected, and a number ofannotation activities are currently going on.

NCBI has supplied their latestgenome assembly (build 30).

EBI provided a non-redundant SwissProt/TrEMBL protein set.

The H-Invitational Dataset

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H-InvDB [G-integra]

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Integrative Annotation of 21, 037 Human Genes Validated by Full-Length cDNA Clones

Tadashi Imanishi1, Takeshi Itoh1, Yutaka Suzuki2, Claire O'Donovan3, Satoshi Fukuchi4, Kanako O. Koyanagi1,5, Roberto A. Barrero1,5, Takuro Tamura6,7, Yumi Yamaguchi-Kabata1, Motohiko Tanino1,5, Kei Yura8, Satoru Miyazaki4, Kazuho Ikeo4, Keiichi Homma4, Arek Kasprzyk3, Tetsuo Nishikawa9,10, Mika Hirakawa11, Jean Thierry-Mieg12,13, Danielle Thierry-Mieg12,13, Jennifer Ashurst14, Libin Jia15, Mitsuteru Nakao2, Michael A. Thomas16, Nicola Mulder3, Youla Karavidopoulou3, Lihua Jin4, Sangsoo Kim17, Tomohiro Yasuda10, Boris Lenhard18, Eric Eveno12,19, Yoshiyuki Suzuki4, Chisato Yamasaki1, Jun-ichi Takeda1, Craig Gough1,5, Phillip Hilton1,5, Yasuyuki Fujii1,5, Hiroaki Sakai1,5, Susumu Tanaka1,5, Clara Amid20, Matthew Bellgard21, Maria de Fatima Bonaldo22, Hidemasa Bono23, Susan K. Bromberg16, Anthony Brookes18, Elspeth Bruford24, Piero Carninci25, Claude Chelala12, Christine Couillault12,19, Sandro J. de Souza26, Marie-Anne Debily12, Marie-Dominique Devignes27, Inna Dubchak28, Toshinori Endo29, Anne Estreicher30, Eduardo Eyras14, Kaoru Fukami-Kobayashi4, Gopal Gopinathrao16, Esther Graudens12,19, Yoonsoo Hahn17, Michael Han20, Ze-Guang Han19,31, Kousuke Hanada4, Katsuyuki Hashimoto32, Ursula Hinz30, Momoki Hirai33, Teruyoshi Hishiki7, Ian Hopkinson34, Sandrine Imbeaud12,19, Hidetoshi Inoko1,5,35, Alexander Kanapin3, Takeya Kasukawa23, Janet Kelso36, Paul Kersey3, Reiko Kikuno37, Kouichi Kimura10, Bernhard Korn38, Vladimir Kuryshev39, Izabela Makalowska40, Takashi Makino4, Shuhei Mano1,5, Regine Mariage-Samson12, Jun Mashima4, Hideo Matsuda41, Hans-Werner Mewes20, ShinseiMinoshima42, Keiichi Nagai10, Hideki Nagasaki43, Rajni Nigam16, Osamu Ogasawara2, Osamu Ohara37, Masafumi Ohtsubo42, Norihiro Okada44, Toshihisa Okido4, Satoshi OOta45,46, Motonori Ota47, Toshio Ota48, Tetsuji Otsuki49, Dominique Piatier-Tonneau12, Shuang-Xi Ren19,31, Naruya Saitou46, Katsunaga Sakai4, Shigetaka Sakamoto4, Ryuichi Sakate33, Ingo Schupp39, Florence Servant3, Stephen Sherry50, Nobuyoshi Shimizu42, Mary Shimoyama16, Andrew J. Simpson26, Bento Soares22, Charles Steward14, Makiko Suwa43, Mami Suzuki4, Aiko Takahashi1,5, Gen Tamiya5,35, Hiroshi Tanaka29, Todd Taylor51, Joseph D. Terwilliger52, Per Unneberg53, Shinya Watanabe2, Laurens Wilming14, Norikazu Yasuda1,5, Hyang-Sook Yoo17, VamsiVeeramachaneni40, Marvin Stodolsky54, Wojciech Makalowski40, Mitiko Go55, Kenta Nakai2, Toshihisa Takagi2, Minoru Kanehisa11, Yoshiyuki Sakaki2,24, John Quackenbush56, Yasushi Okazaki23, Yoshihide Hayashizaki23, Winston Hide36, RanajitChakraborty57, Ken Nishikawa4, Hideaki Sugawara4, Yoshio Tateno4, Zhu Chen19,31,58, Michio Oishi37, Peter Tonellato16, Rolf Apweiler3, Kousaku Okubo7,59, Lukas Wagner50, Stefan Wiemann39, Robert L Strausberg15, Takao Isogai9,60, Charles Auffray12,19, Nobuo Nomura7, Takashi Gojobori1,4,61*, & Sumio Sugano2,7

(153 authors) PLOS Biology, June (2004)

(3) The Genome Network Project(2004-2008)

Genome Functional Network Analysis

Biological Functional Analysis

Technology Development for Genome Network Analysis

　--- Matrix Research System

Large Scale Data Production HorizontalIndividual Biological/Medical Analysis Vertical

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Cancer related gene Genome analysis

Diabetes related geneGenome analysis

Brain related gene Genome analysis

Cancer related protein-protein(DNA) interaction

Diabetes related protein-protein(DNA) interaction

Brain related protein-protein(DNA) interaction

Cancer related （cDNA）analysis

Diabetes related （cDNA）analysis

Brain related（cDNA）analysis

Cancer Research Gr Diabetes Research Gr Brain Research Grindividual research group

Small scalescreening

Small scale screening

Small scaleScreening

Traditional approach

Toward molecular system network which connect cancer symptom

and cancer related gene

Toward molecular system network which connect diabetes symptom

and diabetes related gene

Toward molecular system network which connect brain function and

brain related gene

New research style for post-genome era

Molecular System networkwhich connect cancer symptom

and cancer related gene

Molecular System network which connect diabetes symptom and

diabetes related gene

Molecular System network which connect brain function and brain

related gene

Genome NetworkGenome Networkdatabasedatabase

Genome wide Screening ServiceLarge scale center can provide services as if they are inIndividual research group

Genome project

Full-length cDNA Project

Large Scale C

enter

Identification of gene cancerrelated expression region and transcriptional factor

Identification of diabetesrelated expression region and transcriptional factor

Identification of brainrelated expression region and transcriptional factor

Cancer related proteinlocalization in cell

Diabetes related proteinlocalization in cell

Brain related proteinLocalization in cell

Transcriptional reguratory regionProtein (transcriptional factor) – DNA（gene expression region）interaction

Protein-protein interaction, Protein-DNA interaction

Protein localization in cell　etc.

Genome Structural Genome Structural databasedatabase

genome、gene（full-lengthcDNA）protein structure, SNP, HAPMap

Genome Project （consortium data open to public）

Full-length cDNA Project

We have already had largescale analysis.

Transcriptional reguratory regionProtein (transcriptional factor) – DNA（gene expression region）interaction

Protein-protein interaction

Protein localization in cell　etc.

Genome FunctionalGenome Functional　　　　　　databasedatabase

Systematic System Biology

Yoshihide Hayashizaki

Genome Functional Database Expression regulatory regionExpression ProfileProtein-Protein interactionIntracellular expression profileQuantitative analysis of Protein-RNA intracellular expressionProtein-DNA interactionProtein-RNA interactionhigh-throughput in situ hybridizationQuantitative analysis of intracellular dynamic kinesis of Protein-RNAAnalysis of variant transcriptsNon-coding RNA analysisSense-Antisense RNAetc.

(4) Protein 3000 Project (2002-2006)

Structural Genomics / ProteomicsTo determine protein structures genome-widely

Japan started the project in 1998 at RIKEN/GSCUSA started the project in 2000 at 9 centers

World Meeting on Structural Genomics Virginia, USA 4 Apr. 2001

The Agreement--10,000 Protein Family Structures should be solved

-- 30% will be done in Japan 2,500 -- RIKEN -- RSGI

500 -- 8 groups of individual interest

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RIKEN Structural Genomics/Proteomics Initiative (RSGI)

High-throughput and large-scale structural determination by X-ray crystallography and NMR spectroscopyFor structural determinations, we use both X-ray crystallography and NMR spectroscopy to the same extent. The determinations of 150 structures/year are currently being conducted. For X-ray crystallography, in addition to other structural biology beamlines, two beamlines at SPring-8 in Harima, dedicated to structural genomics have been in use. The NMR methods can be applied for proteins that do not crystallize and proteins that are in near-physiological conditions. A large NMR facility at GSC has been established, and is currently equipped with forty machines.

SPring-8 synchrotron facility RIKEN GSC NMR facility

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1A8H1B7F

1BJW 1EE8

1GD8

1GD7

1GAX1G59

1HLV

1HZD1ILE

1IOZ 1IPA

RIKEN Structural Genomics/Proteomics Initiative (RSGI)Crystal (in PDB)

1IQR 1IQU

1GLN

1IQ0

1D2M

1H38

1E7Z 1FL0

RIKEN Structural Genomics/Proteomics Initiative (RSGI)Crystal (in PDB)

1IVO1IVS

1IQ8 1IT7 1IT8

1IU3

1IV21IV1 1IV3 1IV4

1IRX1IR6

1IUH

1IYW1IW7

1IZ9

1IOM

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RIKEN Structural Genomics/Proteomics Initiative (RSGI)Crystal (in PDB)

1J2B

1J3B

1J09 1N75 1N77 1N78

1J1V

1J33 1J3N

1JZQ 1JZS

1KA9

1J1Z 1J20 1KH2 1KH3 1KOR

1J1U

1KH1

RIKEN Structural Genomics/Proteomics Initiative (RSGI)Crystal (in PDB)

1NZA

1OI7

1UFV

1UG6 1UIY

1OD6 1ODE 1ODI 1ODJ

1ODK

1UAY 1UB0 1UB3

1UB7 1UEK

1QQT

1KN0

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1QQI

RIKEN Structural Genomics/Proteomics Initiative (RSGI)NMR (in PDB)

1AA3 1AA9 1B22 1BW6 1D8J 1D8K 1D8Z 1D9A

1FE5 1FJD 1INZ 1IQ3 1IUF 1IVZ

1KOY

1PMS 1RRB 1U2F 2SXL 2U2F1MG8

1J1H1IW5 1IXD 1IYR1IYG1IYF

1FEX

RSGI Research

Determination of Protein 3D Structures

FY 2002：150 structures (NMR : 75 & X-ray : 75)

FY 2003：360 structures (NMR : 207 & X-ray : 153)Major targets at higher eukaryotes’ proteine.g. Human (approximately half)

FY 2004：620 structures (NMR : 300 & X-ray : 320)expected

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RSGI Partner

Comprehensive analyses of protein structure and function

Applied Research

Comprehensive analyses of protein structure and function

Applied Research

Industrial R & DIndustrial R & D

Instant release

Technology transfer in the Protein 3000 ProjectPartner Project

- Drug Discovery Collaboration System -

Web

Technology transfer in the Protein 3000 Project

Information on Targets

High-throughputScreening

High-throughputScreening,

Optimization of Compounds

Proteomic Drug Discovery

Targetselection

Protein Expression Structural and Functional Analysis

Basic collaborative research

COMPANY

Sample Coordinate Basic Patent

Patents relating to candidate compounds for drug

Individual collaborative research

In silicoOptimization of

Compounds

RIKEN

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Omic-space

By Prof. A. Wada

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Integrative Biology

Phenome

MetabolomeSystems Biology

ProteomeBioinformatics

Transcriptome

Genome

References (by Toru YAO) in Japanese / * in English as of Dec.2004

(18) Synopsis; Bioinformatics and Systems Biology-towards Integrative Biology IMIA Yearbook of Medical Informatics 2005 (in press)*

(17) World Situation of Genome Network Analysis PNE (Protein, Nucleic Acid and Enzyme) 49, 2993-3000 (2004)

(16) Bioinformatics in India PNE 49, 2160-2165 (2004)

(15) Special Issue “Frontier of Systems Biology” ( Kitano, Tomita, Ueda, Yao et. al) Bio Industry 21, 5-67 (2004)

(14) World Trends of Bioinformatics and Systems Biology –Towards Integrative Biology PNE 49,171-174 (2004)

(13) Report –Symposium on the Elucidation of “Strategy of Life” (2003.5.23) Kagaku (Science) 73,925-927 (2003)　

(12) From Genome-Gene-Protein Analysis to Biological Systems Analysis Petrotech. 26,451-457 (2003)

(11) Bioinformatics in the New Genomic Era Chemical Industry　54,35-40 (2003)

(10) 'Bioinformatics for the Genomic Sciences and towards the Systems Biology’　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　 　 Progress in Biophysics and

Mol. Biol. 80, 23-42 (2002)*(9) World Trends--From Genome Informatics to Systems Biology PNE 49,1229-1235 (2002)(8) 'Bioinformatics and Systems Biology in the Post-Genome Era’ CHI Symposium in Tokyo in February 2002*

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　　　ThanksRIKEN/GSC Members

A.Wada, Y.Sakaki, H.Hayashizaki, S.Yokoyama,H.Shinozaki, T.Shiroishi, A.Konagaya et.al.

AIST/JBIRC T.Gojyobori et al.

AIST/CBRC Y.Akiyama et.al.

Bioinformatics and Systems BiologyResearchers in Japan and World