The GUDMAP Database: An Online Resource for Genitourinary Research Dr. Simon Harding

1. The GUDMAP Database: An Online Resource for Genitourinary Research Dr. Simon Harding Stem Cells & Bioinformatics 22nd September 2009

2. Overview • GUDMAP: Introduction • The Data • In Situ, Microarray and statistics • The Website • Basic features – browsing and querying • Additional tools – gene expression summaries, disease resource • Examples of Use • Complex Boolean anatomy query kidney Reproductive system

3. GUDMAP: Introduction • GenitoUrinary Development Molecular Anatomy Project • Goal: Provide the scientific research community with tools to facilitate research through a molecular atlas of gene expression in developing organs of mouse GU system • Worldwide consortium based project • USA • Australia • UK – Edinburgh • Funded by NIH, NIDDK

4. GUDMAP: Introduction • Why GUDMAP? • Community resource to enhance existing research and stimulate new research • High resolution molecular anatomy of the developing GU system • Markers for anatomically defined cell types • Describe developmental processes that establish function domains • Understand genesis of organ anatomy at molecular/cellular level • New level of understanding to benefits treatment of disorders and disease of GU system • GUDMAP Edinburgh • Human Genetics Unit & University of Edinburgh • Curating data and making it accessible through a website • Raw data available to research community • Easy-to-use window onto this data – web-interface

5. GUDMAP: In Situ Data • In situ data • In situ hydbridisation (section & wholemount) • Immunohistochemistry (section) • In situ analysis of transgenic reporter screens (wholemount) GUDMAP:7156 GUDMAP:11296

6. GUDMAP: Microarray Data • Microarray data • Array analysis of laser-captured components of developing GU system - enrichment • Array analysis of FACS-isolated cells from transgenic reporter mice - purification

7. GUDMAP: Statistics

8. GUDMAP: The Website QUERY gene anatomy function boolean anatomy FOCUS Focus query to distinct anatomical groups BROWSE Microarrays, in situs, by stage, genes

9. GUDMAP Entry Details • Search result

10. Annotation in a GUDMAP entry Annotation Notes High resolution ontology Signal is strongest on the side of the vesicle furthest from the ureteric tip

11. Adjust parameters Select components from tree Syntax allows for more advanced queries

13. GUDMAP: Gene strip • Summarising gene expression In situ expression entries Microarray expression Gene Page Disease Associations In situ image matrix

14. GUDMAP: Linking to disease • Why? • Link between gene expression, GU development and GU disease • Studying gene expression in the genitourinary (GU) system is useful to understand GU disease. • If we know that a particular disease affects the GU system we can look at which genes are expressed (or not expressed) in the affected GU tissues and structures. • Help to better understand aetiology of disease. • Some diseases occur as a consequence of events taking place during development, e.g. incorrect formation of structures.

15. GUDMAP: Linking to disease • Disease Resource • Associations between genes and OMIM disease • Associations between genes and mammalian renal/urinary/reproductive phenotypes (MGI) • Disease-gene associations are searchable with results presented in a simple table. OMIM: Online Mendelian Inheritance in Man (www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM) NCBI: National Center for Biotechnology Information (www.ncbi.nlm.nih.gov/) MGI: Mouse Genome Informatics (www.informatics.jax.org)

16. GUDMAP: Example • What genes specifically mark the structure I am interested in examining? • Ureteric Tip • Looking for gene expressed in ureteric tip but not in surrounding structures • Strategy - use Boolean Anatomy Query

17. What genes specifically mark the structure I am interested in examining?

18. What genes specifically mark the structure I am interested in examining? • Boolean Query syntax – to build complex query • Save larger queries to a file or in collections Query for ureteric tip at TS23 (E15.5) GENE: nd{in cap mesenchyme TS23..TS23} AND | nd{in early tubule TS23..TS23} AND | nd{in late tubule TS23..TS23} AND | nd{in renal vasculature TS23..TS23} AND | nd{in ureter TS23..TS23} AND | p{in ureteric tip TS23..TS23}AND | nd{in ureteric trunk TS23..TS23} AND | nd{in renal interstitium group TS23..TS23}

19. What genes specifically mark the structure I am interested in examining?

20. What genes specifically mark the structure I am interested in examining?

21. Acknowledgements Harvard University Andy McMahon et al University of Queensland Melissa Little et al Peter Koopman et al Sean Grimmond et al Cincinnati Children's Hospital Medical Center Bruce Aronow et al Steve Potter et al Jim Lessard et al Columbia University Cathy Mendelsohn et al Vanderbilt University Michelle Southard-Smith et al Research Triangle, NC Kevin Gaido et al University of Edinburgh & MRC Human Genetics Unit GUDMAP Editorial Office Duncan Davidson Jamie Davies Jane Armstrong Jane Brennan Sue Lloyd-MacGilp Chris Armit GUDMAP Database Development Team Derek Houghton Mehran Sharghi Xingjun Pi Ying Cheng Koosum Roochun