1. NCBC “Big P” Activities Russ Altman on behalf of NCBC PIs and NIH/NCBC Staff

2. What are big P and little P? Two ways to build infrastructure Little P = the individual NCBC center programs pursuing the creation of computational infrastructure in focused areas. Big P = cross-NCBC program efforts to create more general infrastructure that is best and most efficiently done together.

3. Three NCBC Working Groups 1.Biositemaps 2.Ontologies 3.Driving biological problems & aggregate impact of NCBC program

4. WG#1: Biositemaps/Resourcome CHALLENGE: Need for widely-available and recognized technology for inventory and integration of NIH resources. SOLUTION: Biositemaps--borrows Google sitemaps idea of distributed descriptions of resources for search, indexing and aggregation. Features minimal central control. iTools; Dinov ID, Rubin D, Lorensen W, Dugan J, Ma J, Murphy S, Kirschner B, Bug W, Sherman M, Floratos A, Kennedy D, Jagadish HV, Schmidt J, Athey B, Califano A, Musen M, Altman R, Kikinis R, Kohane I, Delp S, Parker DS, Toga AW. "iTools: a framework for classification, categorization and integration of computational biology resources." PLoS ONE 2008; 3(5): e2265. PMID: 18509477.iTools: a framework for classification, categorization and integration of computational biology resources." PLoS ONE 2008; 3(5): e2265. PMID: 18509477. Cannata N, Merelli E, Altman RB (2005) Time to Organize the Bioinformatics Resourceome. PLoS Comput Biol 1(7): e76. doi:10.1371/journal.pcbi.0010076

5. Google Sitemaps

6. Biositemaps (ncbcs.org/biositemaps)

7. Aggregating Resources from Biositemaps <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> <desc:<desc:resource_name>Virtual Jeff Ma Jeff Ma</desc:<desc:URL>http://www.loni.ucl<desc:version_information><desc:Version_Information><desc:version>1.1.0</desc <desc:release_date rdf:dat <desc:development_stage>De</desc:Version_Information></desc:version_information> The Virtual Fil The Virtual Fil CCB License CCB License</des<desc:resource_type><BRO:Data_Transfer/></desc:resource_type> iTools Open Biomedical Resources Distributed biositemap files Any Semantic Web tools

8. NCBO Biositemap Authoring Tool

9. iTools: Biositemaps Authoring and Consuming

10. Future Efforts of the Working Group Finalize pubic sites www.ncbcs.org/biositemaps Users and Developers –Easy-to-use Biositemaps publishing tools –FAQ and help for users and sysadmin Continued development and maintenance of NCBO-BioPortal- Biomedical Resource Ontology (BRO) Continued efforts to align methods with similar efforts such as Neuroscience Information Framework (NIF) Outreach to generate community adoption of Biositemaps and related efforts (including “BISTI compendium” of gov’t efforts) Continued research on software and data integration (e.g., pipelining) methods using Biositemaps as enabling technology

11. WG#2: Ontologies Challenge : Identify and disseminate ontology best practices for NCBC program and beyond Categorization of existing bio-ontologies – Recommended (e.g., GO, LOINC, RxNORM) – Recommended with reservations (e.g., ICD, SNOMED) – Promising, but under construction (e.g., OBI) – Unusable (no clear agreeement) Dissemination of recommendations on the Web Identification of areas for ontology development, leading toNCBO dissemination activities (e.g., cellular networks) Manuscript in preparation

12. Future efforts of the working group Publish position paper on ontology evaluationand use Survey ontology needs of NCBCs--both big Pand little P Coordinate action items to address unmetontology-related needs

13. WG#3: Driving Biological Problems (DBPs) and NCBC Impact

14. WG#3: Driving Biological Problems and Impact Challenge: Maximize impact of NCBC program by magnifying the impact of individual DBP success on scientific communities NCBCs.org web portal NCBC tools web page (consuming Biositemaps content, e.g. itools) NCBC Publications Page (http://www.ncbcs.org/ahm2008.html)http://www.ncbcs.org/ahm2008.html Links to individual centers 2008 Meeting Outreach & Coordination Computational Systems Bioinformatics Conference x 2 AMIA Translational Bioinformatics Summit Panels x 2 ISMB NCBC Demonstrations 2008 All Hands Meeting Planning/Coordination

15. Driving Biological Problems I Type I & II Diabetes Asthma Hypertension Obesity Cardiovascular disease B-cell cancers Melanoma Prostate CA Multiple Sclerosis Rheumatoid arthritis Lupus Depression Bipolar disorder Schizophrenia Alzheimer’s disease Age-related brain atrophy Huntington’s disease Autism Cerebral palsy Defects of corpus callosum Velocardiofacial syndrome Development of language Brain changes in HIV HIV clinical trials

16. Driving Biological Problems II Transcription factor specificity Genetics of brain morphology Epigenetics Mapping zebrafish phenotypes Mapping drosophila mutations Cadherin binding mechanisms Myosin function & dynamics RNA structure & dynamics Protein folding

17. Future efforts of the working group Expand WG to include participation from all NCBCs Continue upgrade and maintenance of NCBCs.org –DBP inventory and best practices survey –Creation of NCBC Wikipedia page linked to NCBCs.org 2009 NCBC Conference/Meeting Planning –AMIA Translational Bioinformatics Summit –NCBC AHM –Others TBD Create and Implement Strategy to Interact with CTSAs –Build from i2b2, NCIBI, and NCBO base of Activities –Becich (UPMC)/Athey (U-Mich) CTSA Administrative Supplement for CTSA tools inventory interacting with NCBC WG1

18. NCBC Impact Assessment: Publications 785 total publications from the 7 centers –Most listed at NCBCs.org –Also lists top 2 papers from each center KEY POINT: These papers are generally “full service” papers associated with (1) software, data, models, support materials, and (2) NCBC staff willing to assist motivated users to use the associated tools. None of this is typical of R01-supported publications.

19. Other Big P Activities

20. “Building bridges” Post-doc Program Simbios + National Center for Nanomolecular Imaging: –physics-based interpretation of cryo-EM images CCB + Johns Hopkins University: –tools for diffusion tensor imaging (DTI) analysis I2B2 + University of Utah –Test I2B2 infrastructure on asthma and colon cancer MAGNET + Harvard Integrated Cancer Biology Center –Identify target drugs and phenotypes using connectivity map NA-MIC + UCSD BIRN –Add microscopy image analysis capability to NAMIC Kit NCIBI + Washington University –Co-morbidity analysis of Bipolor Disorder and Nciotine Addition (Fall ‘08) NCBO + Pharmacogenomics Knowledgebase (PharmGKB) –Prototype ontologies for drug response phenotypes

21. Collaborating grants program (R01/R21) All centers participate. Substantial effort to support proposals. 18 awarded to date.

22. Project PI Name(s) Institution Title R01 EB005973-01A1 GROSLAND, NICOLE M UNIVERSITY OF IOWA Integrating Automated Mesh Development into the NA-MIC Toolkit R01 EB006266-01 GEE, JAMES C UNIVERSITY OF PENNSYLVANIA Shape Optimizing Diffeomorphisms for Computational Biology R01 EB006735-01 VAN DEN BOGERT, ANTONIE J CLEVELAND CLINIC LERNER COL/MED-CWRU Efficient Methods for Multi-Domain Biomechanical Simulations R01 AA016748-01 DAUNAIS, JAMES B WAKE FOREST UNIVERSITY HEALTH SCIENCES Measuring Alcohol and Stress Interactions with Structural and Perfusion MRI R01 AR056201-01 BLEMKER, SILVIA S.; THELEN, DARRYL G (contact) UNIVERSITY OF WISCONSIN MADISON Biocomputation of the Links Between Muscle Morphology, Coordination and Injury R01 CA124377-01 CLEARY, KEVIN R GEORGETOWN UNIVERSITY An Integrated System for Image-Guided Radiofrequency Ablation of Liver Tumors R01 CA127979-01A1 CROWLEY, REBECCA S UNIVERSITY OF PITTSBURGH AT PITTSBURGH The ODIE Toolkit - Software for Information Extraction and Biomedical Ontology De R21 GM080216-01 HLAVACEK, WILLIAM S. LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB System-wide Study of Transcriptional Control of Metabolism R01 GM080399-01 KOEHL, PATRICE A UNIVERSITY OF CALIFORNIA DAVIS Geometric-based and Physics-based Simulations of RNA Folding R01 GM083649-01A1 HUNTER, LAWRENCE E UNIVERSITY OF COLORADO DENVER/HSC AURORA Ontologies and Biomedical Language Processing R01 HL087706-01 BRINKLEY, JAMES F UNIVERSITY OF WASHINGTON Realizing the potential of reference ontologies for the semantic web R01 NS055380-01A1 NEPTUNE, RICHARD R UNIVERSITY OF TEXAS AUSTIN Development of a SimTK-based framework for hemiparetic walking assessment R01 NS058296-01 MARTONE, MARYANN E UNIVERSITY OF CALIFORNIA SAN DIEGO Ontology-based multiscale investigation of human neurological disease models R01 CA124380-01A1 SANDER, CHRIS SLOAN-KETTERING INSTITUTE FOR CANCER RES Application of MAGNet Tools to Gene Regulatory Networks in Cancer R01 HL086418-01A1 HUMPHREY, JAY D TEXAS ENGINEERING EXPERIMENT STATION Biomechanical Simulation of Evolving Aortic Aneurysms for Designing Intervention R01 HL087773-01A1 Young, Alistair Andrew UNIVERSITY OF AUCKLAND The Cardiac Atlas Project: Establishment of a Cardiac MRI Database. R01 HL087795-01A1 SHETH, AMIT P WRIGHT STATE UNIVERSITY Semantics and Services enabled Problem Solving Environment for Trypanosoma cruzi R01 NS055383-01A2 Higginson, Jill UNIVERSITY OF DELAWARE Muscle Morphology Strength and Compensatory Strategies Folowing Stroke

23. Collaborator locations U. Iowa U. Pennsylvania Cleveland Clinic Wake Forest Health Sciences U. Wisconsin Georgetown U. Pittsburgh Los Alamos National Lab U. C. Davis University of Colorado Denver U. Washington U.T. Austin U.C. San Diego Sloan Kettering Texas Engineering Experiment Station U. Auckland Wright State U. Delaware Institutes: EB, AR, AA, CA, GM, HL, NS

24. Integrating Automated Mesh Development into the NA-MIC Toolkit Shape Optimizing Diffeomorphisms for Computational Biology Efficient Methods for Multi-Domain Biomechanical Simulations Measuring Alcohol and Stress Interactions with Structural and Perfusion MRI Biocomputation of the Links Between Muscle Morphology, Coordination and Injury An Integrated System for Image-Guided Radiofrequency Ablation of Liver Tumors The ODIE Toolkit - Software for Information Extraction and Biomedical Ontology De System-wide Study of Transcriptional Control of Metabolism Geometric-based and Physics-based Simulations of RNA Folding

25. Realizing the potential of reference ontologies for the semantic web Development of a SimTK-based framework for hemiparetic walking assessment Ontology-based multiscale investigation of human neurological disease models Application of MAGNet Tools to Gene Regulatory Networks in Cancer Biomechanical Simulation of Evolving Aortic Aneurysms for Designing Intervention The Cardiac Atlas Project: Establishment of a Cardiac MRI Database. Semantics and Services enabled Problem Solving Environment for Trypanosoma cruzi Muscle Morphology Strength and Compensatory Strategies Folowing Stroke

26. Other activities deserving note Individual software dissemination sites for each center, integrated at ncbcs.org and itools Other collaborations for each center = TNTC (too numerous to count) Workshops for training and dissemination of software Formal thematic symposia Newsletters, User manuals, Magazine “Challenge” meetings for NLP & Systems Bio Underrepresented minority program (I2B2)

27. Closing thoughts Little P activities provide core strength and focused tools from NCBC program Big P activities magnify the impact of these tools, and connect NCBC centers with other biomedical computation efforts With this good start, the next five years of will bring a national biomedical computational infrastructure envisioned in the BISTI 1999 report.

28. Thanks russ.altman@stanford.edu

29. iTools: Biositemaps Authoring and Consuming

31. Another example of biositemaps is the content for the Compendium of government initiatives with elements of biomedical informatics and computational biology: Google “BISTI Compendium”. This will be implemented using biositemaps in the coming month