1. Web Portal Service on Open Bioinformatics Grid (OBIGrid) Konagaya Akihiko RIKEN GSC Bioinformatics Group Life Science Grid Symposium

2. Outline OBIGrid and Bioinformatics Applications OBISgd: Scalable Genome Database OBITco: Thermus Thermophilus Cyber Outlet OBIYagns: Yet Another Gene Network Simulator

3. OBIGrid (Open Bioinformatics Grid) Genome DB mirror PC Cluster Internet Site-A Site-BSite-D Site-C Seq. anal. program DB search program MD simulation program Cell simulation program PC Cluster node with MDM XMLDB VPN-FW Isolation by VPN+FW Authentication by Globus Connection via Internet Current Status (2003 March) Academic 11 ・ Company 9 ・ NRI 5 CPU 203 nodes 115

4. Other local users not permitted to OBIEnv Access Job Dispatcher Node Search Node Set Globus Tool Kit Jobs Globus Tool Kit Job Acceptance DB Resource Manager SW HW Job Execution Workers Results Scanning Environment My Script OBIEnv Users Portal Application Resource Searcher Mapping of Local user account To Grid User Account Or Public User Account Local Authentification OBIEnv: Bioinformatics Environment (Sato) Single Account Script Prog. Env. Parallel BLAST/DB

5. Web Applications

6. Issues in Integrated Database How to deal with huge datasets? How to deal with heterogeneous datasets? Scalable XML Database Search System Computational Pipeline and Gene Annotation Support System

7. Issues in Cell Simulation How to estimate unknown parameters? How to validate simulation models? Differential Equation Simulation + Genetic Algorithm Biological Experiments/ Literature Information Requires Enormous Computation Infrastructure for data/model/knowledge sharing

8. OBISgd: Distributed XML DB Browser XML DB index search XML DB XML DB ｓ index search index search index search Distributed Index Search Servers Web portal JAVA API Perl API Scalability Quick Response High reliability ＤＤＢＪ－ＸＭＬ ＳＯＡＰ

9. Parallel Search Engine System Configuration ＤＤＢＪ－ＸＭＬ ＳＯＡＰ ＤＤＢＪ－ XML DB ｓ ＤＤＢＪ－ XML DB ｓ ＤＤＢＪ－ XML DB ｓ Search index ＰｏｓｔｇｒｅＳＱＬ Search index ＰｏｓｔｇｒｅＳＱＬ Search index ＰｏｓｔｇｒｅＳＱＬ Search index ＰｏｓｔｇｒｅＳＱＬ Ａｐａｃｈｅ Ｗｅｂ Server Ｔｏｍｃａｔ ＸＳＬ Ｔ ＸＳＬ ＳＯＡＰ Server File Server ddbjbct1/AB000100.xml AB000100 2992 BCT Parameter ： AB000100 getXML_DDBJEntry Web Browser Candidate Entry List SELECT * FROM bct1_3 where val like 'BCT%' XML HTML

10. Experimental Analysis Data Annotation on Molecular Function Protein Interaction Database 3D structure database OBITco: Thermus T. Cyber Outlet Literature Database Genome Sequence Database >S53477 PIR2 release 73.00 MAAIRDYKTALDLTKSLPRPDGLSVQELMDSKIRGGLAYNDFLILPGLVD FASSEVSLQTKLTRNITLNIPLVSSPMDTVTESEMATFMALLDGIGFIHH NCTPEDQADMVRRVKNYENGFINNPIVISPTTTVGEAKSMKEKYGFAGFP VTADGKRNAKLVGAITSRDIQFVEDNSLLVQDVMTKNPVTGAQGITLSEG NEILKKIKKGRLLVVDEKGNLVSMLSRTDLMKNQKYPLASKSANTKQLLW GASIGTMDADKERLRLLVKAGLDVVILDSSQGNSIFQLNMIKWIKETFPD LEIIAGNVVTKEQAANLIAAGADGLRIGMGTGSICITQKVMACGRPQGTA VYNVCEFANQFGVPCMADGGVQKHWSYYYQSFGSWFFYCYDGWYVGRYYR ITR Annotation by Researchers Automatic Annotation Biological Experimental Data Integration of All Information Necessary for Whole Cell Simulation

11. System overview Access Manager Thermus server OBIGrid network SSL connection Secure remote annotation by biologists using SSL on Web Browser

12. Annotation system Top page Menu page Annotation page

13. ORF Prediction 4 programs were used to predict ORF regions in contig sequences. –handai (original annotation done by Osaka U.) –bdgf (BioDictionary Gene Finding, by T.Shibuya, IBM) [1] –getorf1 (with standard genetic code) [2] –getorf2 (with bacterial genetic code) getorf is ORF finding and extracting program (part of EMBOSS packages) [1] Shibuya,T., Rigoutsos, I., “Dictionary-driven prokaryotic gene finding”, NAR. 30: pp.2710-2725, 2002 [2] http://www.hgmp.mrc.ac.uk/Software/EMBOSS/Apps/getorf.html

14. Grb2 ShcGrb2 SOS RAS MAPKKKs MAPKs MAPKKs MAPKs PKC PLC PI3K STAT3 STAT1 STAT3 STAT1 Elk-1AP-1 E2F NF-kappaB CyclinD1/cdk4/6 RbE2FRb-p E2F EGFEGF EGF receptor SOS OBIYagns: Cell Simulation Environment Mathematical Modeling Signal Transduction Cell Cycle Web portal Solver JAVA API Perl API ODE Solver for Stiff Problems Unknown Parameter Estimator

15. System Configuration Web browser Web server Task Manager ODE solver GA ODE solver PC Cluster MPI communication Remote Execution (Embarrassing) Parallel Execution of ODE solvers Unknown Parameter Estimation by Real-code Genetic Algorithm Results of Parameter Estimation Expandable to GAGrid (Ono)

16. ⑦ ⑥ ① Selection of reaction type; mass-action, Michaelis-Menten ② Input of kinetic parameters ③ Input of initial concentrations of reactions ④ Input of fitting data ⑤ Input of fitting expressions ⑥ Input of GA parameters, and run GA program ⑦ Display result of parameter estimation ① Operation ③ ② ④⑤

17. Summary OBIGrid is practical grid computing test bed over the Internet. 20 sites are connected via VPN and 203 cpus/ 115 nodes are available. Some Web Applications are operational and frameworks for web portal sites and computational pipelines are under development.

18. OBIGrid Contributors OBITco/ OBIYagns Fumikazu Konishi, Akinobu Fukuzaki, Ryo Umetsu, Noriko Mito, Aki Hasegawa, Mariko Hatakeyama, Kaori Ide （ GSC ） Seiki Kuramitsu, Shigeyuki Yokoyama, Ryoji Masui, Noriko Nakai （ Structurome ） Shuhei Kimura （ GSC ）, Takuji Kawasaki （ FUJI RIC ） OBIEnv/OBISgd Kenji Sato, Xavier Defago （ JAIST ）, Shinichi Tsuji, Yasuhiko Nakajima （ HNES ） Grid WG of Japan Committee on High-Performance Computing for Bioinformatics Grid WG of Initiative for Parallel Bioinformatics Masahiro Okamoto （ Kushu Uni. ）, Isao Ono （ The Uni. Of Tokushima ）, Takahiro Koita （ OSU ）, Hiroshi Someya （ ISM ）, Keisuke Tanaka （ Titech ）, Hideki Nakada （ AIST, Titech ）, Tsuneo Nakanishi （ Kushu Uni. ）, Tomoyuki Hiroyasu （ Dosisha Uni. ）, Akira Fukuda （ Kushu Uni. ）, Satoshi Matsuoka （ Titech ）, Masayuki Yamamura （ Titech ）, Tetsushi Yada （ HGC), Satoshi Miyazaki （ DDBJ ）, Asao Fujiyama （ NII ）, Morikazu Nakamura （ Uni. Of the Ryukyus ）, Hiroyuki Kurata （ KIT ） Kyoko Hirukawa （ JAIST ）， Hiroko Furuno ， Sonoko Endo, Keiko Satake （ GSC ） titles omitted NTT ＤＡＴＡ Corporation Cognitive Research Laboratories, Inc. Hewlett-Packard Japan, Ltd. National Institute of Advanced Industrial Science and Technology SURIGIKEN Co., Ltd. SUMISHO Eelectronics Co., Ltd. NEC Software Hokuriku, Ltd. IBM Japan, Ltd. NIPPON SHINYAKU Co,. Ltd. NEC Corporation FUJI Research Institute Corpration FUJITSU Limited BEST SYSTEMS Inc NIPPON TELEGRAPH AND TELEPHONE WEST Corporation MITSUBISHI RESEARCH INSTITUTE, Inc. RIKEN Yokohama Institute RIKEI Corporation ESCA, Co. INTEC Web and Genome Informatics Corporation CTC LABORATORY SYSTEMS Corporation Staff VPN/Globus net Hiroyuki Umeda （ IBM ） OBIMde Makoto Taiji, Tetsu Narumi, Noriyuki Futatsugi, Naoki Takada （ GSC ）, Tomoyuki Yamamoto （ JAIST ） Leader Akihiko Konagaya (JAIST, Riken)

19. OBIGrid http://obigrid.org