The GUDMAP Database:

An Online Resource for Genitourinary Research

Dr. Simon Harding

Stem Cells & Bioinformatics

22nd September 2009

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 querykidney

Reproductive system

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

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

GUDMAP: In Situ Data

• In situ data• In situ hydbridisation (section & wholemount)

• Immunohistochemistry (section)• In situ analysis of transgenic reporter screens (wholemount)

GUDMAP:11296GUDMAP:7156

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

GUDMAP: Statistics

ISH MA IHC TgGenes Entries Genes Entries Genes Entries Genes Entries

Metanephros2785 5449 - 129 7 9 1 6

Lower Urinary System

2689 4902 - 54 0 0 1 6

Early Reproductive System

227 253 - 11 0 0 0 0

Male Reproductive System

2364 2831 - 33 2 2 1 3

Female Reproductive System

2292 2741 - 15 1 1 1 3

Total2907 7728 - 259 9 12 1 6

GUDMAP: The Website

BROWSEMicroarrays, in situs,

by stage, genes

QUERYgene

anatomyfunction

boolean anatomyFOCUSFocus query to

distinct anatomical groups

• Search resultGUDMAP Entry

Details

Annotation in a GUDMAP entry Annotation Notes

High resolution ontology

Signal is strongest on the side of the vesicle furthest from the

ureteric tip

Select componen

ts from tree

Adjust parameters

Syntax allows for more advanced queries

GUDMAP: Gene strip

• Summarising gene expression

Gene PageGene Page

Disease Associations

Disease Associations

In situ expression

entries

In situ expression

entries

In situ image matrix

In situ image matrix

Microarray expressionMicroarray expression

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.

• 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.

GUDMAP: Linking to disease

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)

• 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

GUDMAP: Example

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}

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

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

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

University of Edinburgh & MRC Human Genetics Unit

GUDMAP Editorial OfficeDuncan DavidsonJamie DaviesJane ArmstrongJane BrennanSue Lloyd-MacGilpChris Armit

GUDMAP Database Development TeamDerek HoughtonMehran SharghiXingjun PiYing ChengKoosum Roochun

Harvard UniversityAndy McMahon et al  University of QueenslandMelissa Little et alPeter Koopman et alSean Grimmond et al

Cincinnati Children's Hospital Medical CenterBruce Aronow et al Steve Potter et alJim Lessard et al  Columbia UniversityCathy Mendelsohn et al

Vanderbilt UniversityMichelle Southard-Smith et al

Research Triangle, NCKevin Gaido et al

Acknowledgements