The Research Institute at Nationwide Children’s Hospital Center for Childhood Cancer BioInformatics Group

1. The Research Institute at Nationwide Children’s Hospital Center for Childhood Cancer BioInformatics Group Tom Barr Dave Billiter, PMP

2. The Research Institute at Nationwide Children’s Hospital

3. Overview • Introduction • Center for Childhood Cancer • C3BIG • Biopathology Center • VIPER • C3BIG Image Dashboard • VM2M • Future Opportunities • Closing

4. Center for Childhood Cancer Areas of Focus • Molecular mechanisms involving pediatric sarcomagenesis • Regulation of survivin gene expression • Stroma/tumor interactions in adult and pediatric cancer • Tumor microenvironment • Gene expression profiling in pediatric leukemias • Signal transduction and pharmacologic interventions • Oncolytic viral therapy in pediatric brain tumors

5. Affiliations and Collaborations • Children’s Oncology Group (COG) • Gynecologic Oncology Group (GOG) • Cooperative Human Tissue Network (pCHTN) • Cancer Therapy Evaluation Program (CTEP) • The Ohio State University Comprehensive Cancer Center • Arthur G. James Cancer Hospital/Richard J. Solove Research Institute • Nationwide Children’s Hospital Division of Hematology and Oncology

6. Center for Childhood Cancer BioInformatics Group (C3BIG) Mission The C3 BioInformatics Group of The Research Institute at Nationwide Children's Hospital, under the direction of Dr. Stephen J. Qualman, is a BioInformatics application development team dedicated to increasing cure rates and decreasing side effects in therapy through Information Technology.

7. C3BIG • Dave Billiter- Informatics Development Manager • Tom Barr – Imaging Manager • Bob Neville- Senior Software Developer • Scott Hargrose- Software Developer/DBA • Bill Beyer- Business Analyst/Software Developer • Heather Bao- Software Developer • Heather Day- Quality Assurance/Tech Writer • Subha Krishnamachary- Software Developer • Andy Fox- Software Developer • Mark Plaskow- Consultant

8. C3BIG User Community • Center for Childhood Cancer • Biopathology Center (BPC) • Biobehavioral Health • Center for Innovation in Pediatric Practice • Research Information Services • Children’s Hospital Inc. • Children’s Oncology Group (COG) • Gynecologic Oncology Group (GOG) • Cooperative Human Tissue Network (CHTN) • Childhood Cancer Survival Studies (CCSS) • Ohio Supercomputer Center (OSC) • Group Banking Committee (GBC)

9. C3BIG Focus Areas • Customized Application Development • Informatics Consulting • Solution Analysis • Data Management • Project Management • Systems Architecture (SOA) • Web Site Development • Digital Imaging/Image Analysis

10. Biopathology Center • The Biopathology Center (BPC) is largely a government funded non-profit organization whose primary objective is the long-term acquisition and storage of a large number of cancer related tissue samples and related data for the purpose of supporting cutting edge research. • Normal tissue and other diseased specimens are also managed by the BPC. • Directed by Dr. Nilsa Ramirez • http://www.biopathologycenter.org/

11. Biopathology Center Components • Biospecimen Repository • Molecular Genetics • Core Morphology • Digital Imaging Core

12. Biopathology Center Organization providing specimen management services for: • Pediatric Cooperative Human Tissue Network (pCHTN) • Children’s Oncology Group (COG) • Gynecologic Oncology Group (GOG) • Childhood Cancer Survivor Study (CCSS) • Clinical Trials Evaluation Program (CTEP) • The Cancer Genome Atlas (TCGA) • Strategic Partnering for the Evaluation of Cancer Signatures (SPECS)

13. BPC by the numbers • Over 650,000 specimens currently in bank • Receive tissues from over 500 hospitals • Receive and process 100 cases or 500 aliquots each day • Distribute over 25,000 specimens annually to over 130 academic and commercial researchers

14. Quality Control • Verification of institutional diagnosis • Documentation of % tumor and % necrosis • Specimens must go through quality control process prior to being served to an investigator

15. Virtual Microscopy • The technique of digitizing microscope slides with common objective magnifications • may be equivalent to original glass slides on microscopes • will provide diagnostic image quality

16. Why Virtual Microscopy? • Eliminate distribution of glass slides, logistical issues with rapid turnaround times, and costs of tracking and lost or broken slides • Support image analysis • Better quality than static images • Accessible anytime via the Internet

17. Scanscope Console Spectrum Information Manager Virtual Slide Manager Web Viewer ImageScope Digital Slide Studio TMALab Digital Slide Conferencing Aperio Scanscope XT (2) Virtual Slide Repository NAS Device Project VIPER 10 Tb storage cluster at the Ohio Supercomputer Center 6 Tb local storage cluster VM Software/Hardware

18. Project VIPER • Virtual microscopy Image Pilot EndeavoR • Web-based pathology review system that is extensible both for today and tomorrow’s research needs • Facilitates a more efficient and cost-effective quality control review process of patient tissue submitted by member institutions • Integration of a virtual microscopy service into the research workflow • Acts as catalyst to advance collaborative pediatric and gynecologic pathology research and research in image analysis

19. Online registration and request for password resets Notified via email of new cases Personalized screen with list of cases and case status after authenticating into VIPER System monitors new cases, completed cases, and cases under review Ability to annotate images Online forms for completion Email notification of completed cases to the BPC User’s manual available online Reviewers

20. Assign Password Assign Cases and/or groups of cases Upload Pathology Reports Add Staff Accounts Add or Remove reviewers Manage Cases Manage Slides Manage Groups Manage Institutions Query for Case status by reviewer or protocol Image Directory Assignment Online User’s Manual Operations Staff

21. VIPER • http://viper.epn.osc.edu/viper/

26. C3BIG Image Dashboard • Slide processor for cancerous diseases • Allows users to query multiple images by morphologic characteristics • Algorithm to detect and measure necrosis • Algorithm to detect and measure abnormal nuclei clustering (anaplasia)

29. Virtual Microscopy to Molecule (VM2M) • Creates a system where Virtual Microscopy data will be available alongside microarray data for disease diagnosis and treatment • Web-based system where a pathologist can search for tissue samples of interest • Reviewer can inspect the corresponding digital image using a web based image viewer, with the ability to zoom and pan to the desired parts of the image. • Reviewer will also have the ability to access the micro- array data corresponding to the same tissue sample, along with results from an automated analysis of the digital image.

30. VM2M Architecture

31. Search Allow the user to search all files stored on the system for the specific criteria. VM2M Web Flow Allow the user to quick search all files stored on the system based on different disease types and Sub disease types Browse Allow the user to upload different types of files such as .svs (digital slides file), .cel (raw microarray file), and .chp (processed microarray file). When .cel file uploaded, MIAME Checklist is required. Home Logged in Upload Files Download Allow the user to download useful files online Registration – Get Account Forget Password? – Get Password User Profile Allow the user to edit the personal information.

32. VM2M Home Page

33. VM2M Login Page

34. VM2M Browser

35. VM2M Search Page

36. VM2M Search Detail Page

37. VM2M Slide Upload Page

38. VM2M Add New Case

39. VM2M Microarray Upload

40. VM2M Download

41. Future Opportunities • COG/GOG Image Warehouse • Pediatric TARGET Tool • caBIG Image Service • Pathology Review Education • VIPER Integration with Aperio Spectrum • Further development of image analysis algorithms

42. Closing • Thank You • Questions?? • Thomas.Barr@NationwideChildrens.org