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Jeff Gregg, M.D.

The Development of an Informatics Platform for the Characterization of Clinical Samples. Jeff Gregg, M.D. Department of Pathology UC Davis School of Medicine. Molecular. Pathology. MPSR. Shared. Resource. Ovarian Cancer Project.

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Jeff Gregg, M.D.

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  1. The Development of an Informatics Platform for the Characterization of Clinical Samples Jeff Gregg, M.D. Department of Pathology UC Davis School of Medicine

  2. Molecular Pathology MPSR Shared Resource

  3. Ovarian Cancer Project • Develop correlative molecular fingerprints for better diagnosis, prediction of outcome, and, ultimately, early biomarker development • Gene expression profiles • Genomic profiles (e.g. gains and losses of DNA)

  4. Ovarian Cancer Project • leading cause of death from gynecologic malignancy in the United States • fourth leading cause of cancer deaths in women in the United States • estimated 26,700 new cases of ovarian cancer were reported in 1996, and approximately 15,000 women will lose their lives to advanced disease • lack of effective screening strategies and the paucity of symptoms and signs in early stage disease • 70% of women with ovarian cancer present with advanced stage disease • Despite surgical debulking and conventional chemotherapy, long term survival for advanced stage ovarian carcinoma rarely exceeds 15-30%

  5. Ovarian Cancer Project • Prognostic factors • Patient age • <50 years old, 5-year survival of 40% • >50 years old, 5-year survival of 15% • Tumor stage • Tumor grade • Residual disease • Second-Look status • Performance status

  6. Ovarian Cancer Project

  7. Ovarian Cancer Project

  8. Ovarian Cancer Project Normal Poorly diff. Adeno Ca Borderline Mucinous

  9. Ovarian Cancer Project • genes upregulated • in the tumors

  10. Ovarian Cancer Project • set of genes • upregulated in • Borderline tumors

  11. Tissue Database Construction- Phase 1 • Easily implemented in multiple labs • Usable for a diverse group of individuals • Computer illiterate to computer savvy • Basic enough that several individuals could troubleshoot and add functionality • Linked over multiple networks • Relatively inexpensive

  12. Projects • Develop a web-based tissue request system • Track requests • Form reports of distribution of tissue • Send out automated emails to ask users about quality of material, grants obtained with material, manuscripts published using the the material • Billing Module

  13. The End Result… • After the chip is scanned, the probes on the array will “light up” • Brighter probes = More cRNA molecules attached = Higher gene expression A microarray image file A gene expression file

  14. Topics of Interest • The Microarray: An overview • Annotation • Data quality

  15. Probe set Common name, functions, description, etc. Accession Number How does Affymetrix organize its data?

  16. Project: Re-Annotation • Every week, NCBI releases re-annotated human genomic data in a large text file • PROJECT: Write a program that takes in an old gene information Excel file, scans the NCBI file for updated info, and properly updates the Excel file. • Catch: The NCBI file is 233 MB of text (it can’t be opened in a word processor)

  17. Commercial Re-annotation Programs

  18. Silicon Genetics’ GeneSpring The Dragon Database Affymetrix’sNetAffx Commercial Re-annotation Programs Program Shortcomings -Failed to annotate all genes -Left out plenty of info on annotated genes -Failed to annotate all genes -Only 500 genes at a time -User-unfriendly -Cannot save info as text file

  19. Projects • Develop an automated reannotation program that would take sequence information from the Affymetrix arrays, blast, reannotate with name, Unigene number, map position…..

  20. Projects Goal: To Establish a ColdFusion interface to interact with 2 in-house ACCESS Databases as well as a, yet undeveloped Database based in Access, SQL, Oracle language. Duties: Write code for Web interface using CF markup language. Ability to consult with project leaders to determine the best way in which to implement design. Link existing databases using SQL language. Skills Required: Advanced HTML skills. Knowledge of CFML and SQL language. Knowledge of Javascript and XML, a plus. Understanding of Web Server design, esp. Microsoft IIs or iPlanet Web Server 6.0. Advanced understanding of, and ability to implement Web Security protocols and equipment.

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