1. caMOD – Cancer Models Database http://cancermodels.nci.nih.gov

2. Cancer models that recapitulate many aspects of the genesis progression clinical course of human cancers are valuable resources to cancer researchers engaged in a variety of basic, translational, clinical, and epidemiological investigations. Preface

3. Comparison to Humans:Comparison to Humans: SmallSmall Large number of offspringLarge number of offspring Short generation intervalShort generation interval Genetic manipulation (e.g. ES cell technologies)Genetic manipulation (e.g. ES cell technologies) Genetic makeup somewhat similar to humansGenetic makeup somewhat similar to humans Why use Animal Models?

4. The Ideal Animal Model Faithfully reflect a human disease Etiology Pathology Genetics Cancers only in the tissue of interest 100% incidence 0% incidence in untreated or unmodified animals Short latency

5. Submission—Data extracted from literature by curators or submitted by scientists. Search– Customizes searches or predefined searches. System Function Administration— User management and review of models. Cancer Models Database (http://cancermodels.nci.nih.gov) The cancer models database (caMOD) is a web-based resource that provides information about animal models for human cancer to the public research community

6. January 2000 Prototype is presented during the Mouse Models of Human Cancers (MMHCC) Steering Committee Meeting MMHCC adopts the Cancer Models Database (caMOD) as one of their initiatives July 2000 NCICB assumes responsibility for caMOD Spring 2001 caMOD 1.0 released (2-tier application) December 2005 caMOD 2.0 released (n-tier application, based on caBIG compliance guidelines) July 2007 caMOD 2.1 achieves Silver compatibility December 2008 caMOD 2.5 released (grid service) September 2009 caMOD 2.5 achieves Silver compatibility June 2010 caMOD 2.6.1 released History

7. 6,009 models 5,922 Mouse models 40 Dog models 12 Rat models 10 Rabbit models 8 Zebrafish models 6 Hamster models 5 Horse models 4 Cat models 1 Goat model 1 Sheep model Status (as of August 31, 2010)

8. The model is the unit of data collection Model Characteristics (e.g. name, phenotype) Genetic Description (transgene, targeted modification, genomic segment, induced mutation, spontaneous mutation) Carcinogenic Interventions (e.g. chemicals, radiation, hormone) Transient Interference (morpholino oligonucleotides, siRNA experiments) Publications Histopathology (e.g. diagnosis, macroscopic and microscopic description) Cell Lines (generated from the model) Therapeutic Approaches (e.g. compound, experiment, result) Images (e.g. image description, staining – stored on image server [caIMAGE]) Microarray Data (link to caArray or other sources) Transplantation Model Availability (from various sources)

9. Submission

10. Submission steps The submitter provides an overview on why and how the model was generated on the Model Characteristics page. The parts Genetic Description, Carcinogenic Interventions and Transplantation offer the opportunity to describe in more detail how the model was generated. Other parts describe the results of experiments performed or observations made on this particular strain.

11. Navigating the submission pages Most parts contain multiple pages Multiple entries per category are possible

12. double transgenic animal crossed with a knock-out animal, treated with UV-light Genetic Description  Enter Transgene  Transgene 1 Genetic Description  Enter Transgene  Transgene 2 Genetic Description  Enter Targeted Modification  Knock-out Gene Carcinogenic Interventions  Enter Radiation  UV-light Example

13. Duplication function Deletion of records Features enabling the user to control data

14. Search

15. Simple Search Advanced Search Table of Contents (predefined searches) Drug Screening Search (comparison of drug screening experiments in yeast models, xenograft models, genetically engineered models and humans) Different Search Types

16. Listing of search results Columns are configurable and sortable Search Results List

17. Search Result Detail Pages

18. Admin

19. Review Process

20. Coordinator - can name screeners and editors - assigns records and comments to screener and editor Screener - initial check of record Editor - scientific reviewer with specific area of expertise Admin – Review of Records

21. Controlled Vocabularies

22. All but the Zebrafish vocabularies are stored in the NCI Thesaurus. Murine Tissue Types Mouse Diagnoses Rat Anatomy Rat Diagnoses Human Anatomy Zebrafish Anatomy Zebrafish Developmental Stages Staining Methods The EVSTree shown is a separate application used for rendering vocabularies. Vocabulary Usage

23. EVS Tree – an Application for rendering Vocabularies

24. Integration with other Data Sources and Applications

25. caMOD has been designed, architected and constructed to facilitate interoperability with other systems, following caBIG guidelines. Information Providers to caMOD: caBIO to retrieve gene info and clinical trials info through remote API EVS to provide concept codes and preferred descriptions for concepts through caBIO EVS API PubMED Jackson Laboratory Resources Rat Genome Database ZFIN –Zebrafish Model Database NCI’s Developmental Therapeutics Program caArray to store microarray data caIMAGE server to store images Other sites that store microarray or image data Interoperability

26. caMOD has been designed, architected and constructed to facilitate interoperability with other systems, following caBIG guidelines. Information Consumers: caMOD provides information to other systems CMAP Websites such as eMice references specific models in caMOD caELMIR caNanoLab (future) CAPR (future) TP53 database at IARC in France (http://www-p53.iarc.fr/) Interoperability

27. UML Model 65 Domain objects with over 300 attributes categorized under caMOD::AnimalModel caMOD::CancerModel caMOD::InVivoModel (Xenograft) caMOD::YeastModel EVSTree utilizes LexEVS 5.x caBIO 4.x is used to retrieve additional information about genes and clinical trials

28. Common Data Elements CDEs for caMOD 2.5 have been loaded into caDSR

29. Vision To create a cancer preclinical study information resource that will provide structured, searchable access to information about preclinical study protocols and outcomes, linked to detailed information about the animal models used, to related human clinical trials information, and to other molecular, pathology, and compound resources.

30. Integration of preclinical and clinical data Linking preclinical trials information to model data Linking to clinical trials information / other clinical information Connect to preclinical and clinical information in other applications Enable comparison across model systems (animal model, cell line, yeast, xenograft, human) Curation Curated information from the literature Add MGI data to MTB data Integrate with Cancer Gene Index project Goals

31. What models have been used in preclinical studies? Which drugs / treatments have been administered? What was the outcome of the experiment? Has the same drug been used in (human) clinical trials? What was the outcome of the clinical trial? Support research questions such as:

32. See us at our poster Contact Application Support Contact a member of the caMOD Team Juli Klemm Maki Duncan Sima Pandya (Tech Lead) pandyas@mail.nih.govpandyas@mail.nih.gov Ulli Wagner ulrike@mail.nih.govulrike@mail.nih.gov Maureen Colbert (Curator) colbertma@mail.nih.govcolbertma@mail.nih.gov Questions?

33. Thank you Thank you for your interest in caMOD! http://cancermodels.nci.nih.gov