1. Functional Genomics Consortium: NIDDK 56947 (Kaestner) and 56954 (Permutt)
Lab Members
Marie Scearce
John Brestelli
Catherine Lee
Athanasios Arsenlis
Phuc Le
Marko Vatamaniuk
Collaborators:
Gerard Gradwohl (Strasburg)
Ihor Lemischka (Princeton)
CBIL
Chris Stoeckert
Elisabetta Manduchi
Greg Grant
Joan Mazzarelli
Phuc Le
Angel Pizzaro
Deborah F. Pinney
Jonathan Crabtree
Shannon McWeeney
Brian Brunk
Consortium
Alan Permutt
Hiroshi Inoue
Doug Melton
Sandra Clifton
Deana Pape
Buddy Brownstein

2. Functional Genomics of the Developing Endocrine Pancreas
cDNA libraries from pancreatic tissue
Consortium libraries (Currently > 34,000 ESTs)
Pancreatic transcripts: 10,364 EST assemblies (from 25,866 mouse ESTs)
Novel transcripts: 3190 assemblies with only consortium ESTs
relevant dbEST libraries
Microarray studies on pancreatic tissue
Genome wide-survey for genes expressed
Pancreas chip
Validated sequences of interest
Novel sequences from libraries
Goal: Identify genes expressed in the developing endocrine pancreas

4. CBIL Project Architecture
PlasmoDB
AllGenes
EPConDB
Sequence & annotation
Gene index (ESTs and mRNAs)
Microarray expression data
experimental annotation
Relational DB (Oracle) with Perl object layer
GUS
RAD

5. RAD GUS EST clustering and assembly Identify shared TF binding sites
TESS (Transcription Element Search Software)
Genomic alignment
and comparative
Sequence analysis
Identify shared
TF binding sites

6. EPConDB: Content and Features
Pancreas clone sets
Panc Chip Clone sets 1.0, 1.5, 2.0
Transcripts found in consortium libraries
Novel transcripts discovered from consortium libraries
Microarray results
Using Incyte’s GEM (genome-wide survey)
Using Panc Chip
Genes expressed in pancreas
AllGenes queries: function, chromosomal location, keyword, accession, libraries
Pathways

7. EPConDB Pathway query

8. EPConDB Boolean Query

9. EPConDB History Query

10. The Future of EPConDB Display new microarray results
Kaestner: labeling study, developmental series, mutant mice
Central repository for pancreatic experiments
2-color cDNA, long oligos, Affymetrix, SAGE, etc.
Provide tools for microarray import/export
MGED: MIAME-compliance, MAGE, Ontology [Standard Annotation]
John Hutton/ Ron Taylor (UCHSC)
Beta Cell Biology Consortium?
Starting point for analysis
Provide tools: Xcluster, PaGE, Speed Normalization Package
Download datasets
Coordinate experiments to facilitate comparison
Integrate experiments
With genomic data (AllGenes), proteomics? Atlases?
Build networks
Goal: Comprehensive understanding of pancreatic gene expression

11. Microarray Analysis: Xcluster
Xcluster provided by Gavin Sherlock 2001

12. Microarray Analysis: Data download

13. Microarray Gene Expression Database group (MGED)
International effort on microarray data standards:
Develop standards for storing and communicating microarray-based gene expression data
defining the minimal information required to ensure reproducibility and verifiability of results and to facilitate data exchange (MIAME, MAGEML-MAGEDOM)
collecting (and where needed creating) controlled vocabularies/ ontologies.
developing standards for data comparison and normalization.
The schema is compliant with the minimum annotations recommended by MGED.
MIAME: Minimum Information About a Microarray Experiment (common set of concepts that need to be captured in a database to describe gene expression experiments adequately for interpretation, reproduction or critical assessment).
MAML: MicroArray Mark-up Language (XML Document Type Definitions of the concepts).

14. Future EPConDB Query Result

15. Microarray Analysis: R statistics

16. Microarray Analysis: PaGE

17. Assembled Transcripts
About 3 million human EST and mRNA sequences used
Combined into 797,028 assemblies
Cluster into 150,006 “genes”
Can identify a protein for 76,771 genes
And predict a function for 24,127 genes
About 2 million mouse EST and mRNA sequences used
Combined into 355,770 assemblies
Cluster into 74,024 “genes”
Can identify a protein for 34,008 genes
And predict a function for 15,403 genes

18. AllGenes Enhancements: Annotated Entries

19. AllGenes Enhancements: Genomic Data

20. Update: Consortium Libraries so far
Total Sequences:
> 29,000
Mouse in DOTS:
21,196
PancreasAssemblies:
7,294
NOVEL
3,122!