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

NCBC “Big P” Activities

Russ Altman

on behalf of NCBC PIs and NIH/NCBC Staff

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.

Three NCBC Working Groups

1. Biositemaps

2. Ontologies

3. Driving biological problems & aggregate impact of NCBC program

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.

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

http://www.ncbi.nlm.nih.gov/pubmed/18509477



Google Sitemaps

Biositemaps (ncbcs.org/biositemaps)

Aggregating Resourcesfrom Biositemaps

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<desc:keywords>The Virtual Fil <desc:keywords>The Virtual Fil <desc:license>CCB License</des<desc:license>CCB License</des

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iTools

Open BiomedicalResources

Distributed

biositemap

files

AnySemantic

Webtools

NCBO Biositemap Authoring Tool

iTools: Biositemaps Authoring and Consuming

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

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 to NCBO dissemination activities (e.g., cellular networks)

• Manuscript in preparation

Future efforts of the working group

• Publish position paper on ontology evaluation and use

• Survey ontology needs of NCBCs--both big P and little P

• Coordinate action items to address unmet ontology-related needs

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

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)• 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

http://www.ncbcs.org/ahm2008.html

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

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

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

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.

Other Big P Activities

“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

Collaborating grants program(R01/R21)

All centers participate.

Substantial effort to support proposals.

18 awarded to date.

Project PI Name(s) Institution TitleR01 EB005973-01A1 GROSLAND, NICOLE M UNIVERSITY OF IOWA Integrating Automated Mesh Development into the NA-MIC ToolkitR01 EB006266-01 GEE, JAMES C UNIVERSITY OF PENNSYLVANIA Shape Optimizing Diffeomorphisms for Computational BiologyR01 EB006735-01 VAN DEN BOGERT, ANTONIE J CLEVELAND CLINIC LERNER COL/MED-CWRU Efficient Methods for Multi-Domain Biomechanical SimulationsR01 AA016748-01 DAUNAIS, JAMES B WAKE FOREST UNIVERSITY HEALTH SCIENCES Measuring Alcohol and Stress Interactions with Structural and Perfusion MRIR01 AR056201-01 BLEMKER, SILVIA S.; THELEN, DARRYL G (contact) UNIVERSITY OF WISCONSIN MADISONBiocomputation of the Links Between Muscle Morphology, Coordination and InjuryR01 CA124377-01 CLEARY, KEVIN R GEORGETOWN UNIVERSITY An Integrated System for Image-Guided Radiofrequency Ablation of Liver TumorsR01 CA127979-01A1 CROWLEY, REBECCA S UNIVERSITY OF PITTSBURGH AT PITTSBURGH The ODIE Toolkit - Software for Information Extraction and Biomedical Ontology DeR21 GM080216-01 HLAVACEK, WILLIAM S. LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LABSystem-wide Study of Transcriptional Control of MetabolismR01 GM080399-01 KOEHL, PATRICE A UNIVERSITY OF CALIFORNIA DAVIS Geometric-based and Physics-based Simulations of RNA FoldingR01 GM083649-01A1 HUNTER, LAWRENCE E UNIVERSITY OF COLORADO DENVER/HSC AURORA Ontologies and Biomedical Language ProcessingR01 HL087706-01 BRINKLEY, JAMES F UNIVERSITY OF WASHINGTON Realizing the potential of reference ontologies for the semantic webR01 NS055380-01A1 NEPTUNE, RICHARD R UNIVERSITY OF TEXAS AUSTIN Development of a SimTK-based framework for hemiparetic walking assessmentR01 NS058296-01 MARTONE, MARYANN E UNIVERSITY OF CALIFORNIA SAN DIEGO Ontology-based multiscale investigation of human neurological disease modelsR01 CA124380-01A1 SANDER, CHRIS SLOAN-KETTERING INSTITUTE FOR CANCER RES Application of MAGNet Tools to Gene Regulatory Networks in CancerR01 HL086418-01A1 HUMPHREY, JAY D TEXAS ENGINEERING EXPERIMENT STATION Biomechanical Simulation of Evolving Aortic Aneurysms for Designing InterventionR01 HL087773-01A1 Young, Alistair Andrew UNIVERSITY OF AUCKLANDThe Cardiac Atlas Project: Establishment of a Cardiac MRI Database. R01 HL087795-01A1 SHETH, AMIT P WRIGHT STATE UNIVERSITYSemantics and Services enabled Problem Solving Environment for Trypanosoma cruziR01 NS055383-01A2 Higginson, Jill UNIVERSITY OF DELAWAREMuscle Morphology Strength and Compensatory Strategies Folowing Stroke

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

• 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

• 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

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)

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.

Thanks

[email protected]

iTools: Biositemaps Authoring and Consuming

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

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

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