1. database of Genotype and Phenotype
Kim Pruitt
(for Matt Mailman)
NCBI

2. Overview
Phenotype
Genotype
Genotype X Phenotype Association

3. Overview Phenotype Genotype Genotype X Phenotype Association
Data tables
Columns are phenotypes
Rows are individuals
Documents (ie: protocols, data collection forms)
Parts of documents linked to variables
Data dictionary
Genotype
Genotype X Phenotype Association
Question for Matt: Data dictionary is a glossary describing the variables? DDictionary provides context information and isn’t made public as a stand alone object - Only parts of the data dictionary are public, variable descriptions are made public. No format requirement – get this in a variety of formats at this time – format restrictions expected in the future.. Not all values are phenotypes (eg date) so called the data ‘variables’

4. Overview Phenotype Genotype Genotype X Phenotype Association
Genotype files directly from vendor
Intensity files (ie: .CEL)
Genotype X Phenotype Association
Oligo microarrays, measuring allelelic biallelic SNPs variant at a position aa/ab/bb. Illumina and affimetrix platforms are two data types that they get data from now. CEL files will be distributed. (determining the intensity is mature technology but calling the genotype is an area of research so if you have the CEL files you can recalculate the genotypes yourself using newer technology – for authorized access only!

5. Overview Phenotype Genotype Genotype X Phenotype Association
Various statistical models and methods
P-value or LOD score for each marker
Filters by P-value, HWE, minor allele frequency
Map phenotypes onto genomic sequence
Question for Matt: Does ‘phenotype’ protocol document also describe the association method and statistical model used?

6. Overview Phenotype Genotype Genotype X Phenotype Association
Obvious expansion potential:
More species; different types of association data (QTL)
Critically important to archive all data:
Submit primary data to appropriate public archive!
Probe DB: primers, resequencing amplicons
dbSTS: STS markers
Maps: UniSTS; Map Viewer
GenBank: ESTs

7. dbGaP Web Site two levels of access - open and controlled
open access to non-sensitive data
study summaries and documents
measured variables and data elements
analysis reports
genome browser
controlled access provides oversight and accountability for use of sensitive datasets involving personal information
De-identified phenotypes and genotypes for individual subjects
Pedigrees

8. Browse Studies http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap
Link back to dbGaP homepage
Instructions
Description of dbGaP
Question: What do you expect to have for “type of study”? What is a sub-study definition? (longitudinal etc)
Currently all whole genome association, will be expanded to other types in future, can expand to other organisms..
Link to study report
List of variables in study
List of documents in study
Automated query to PubMed for genome-wide association study articles

9. Browse Studies by Disease
Expand/collapse
Link to Terms from MeSH vocabulary
Link to study report

10. Advanced Search Fields to be searched
Add any number of search criteria

11. Study Report Citeable unique stable identifier Genotype x phenotype
association or linkage
analyses
search this study
Link to
variable
report
History
Publications
Attribution
Access Rules
Links back to submitter website
Criteria for inclusion/exclusion

12. Variable Report Citeable unique stable identifier
Documents containing a section that
has been linked to this variable
Statistical summary of values for this variable
P-value is red if cases differ from controls

13. Variable Report (continued)
Document name
Section of document that has
been linked to this variable
Link to document

14. Analysis Report
Link back to report for measured or derived variable that was analyzed
Genome browser of analysis results

15. Genome Browser of Analysis Results
Slider filters results less significant than threshold
2MB bins colored to represent the most
Significantly associated marker
Click on bin of interest to
zoom in and see association
in context with other objects
mapped to the same genomic
region
LINK

16. Genome Browser – Higher Resolution
Collapse table
P-value of genotyped marker
Scroll via
boxes
above
Add maps
CFH gene has been
associated with AMD
in several studies

17. Coming Soon… Studies Features Early 2007 Spring 2007 Summer 2007
Michael J. Fox Foundation Parkinson’s Disease Study (LEAPS)
NINDS Stroke and ALS
Spring 2007
GAIN (Genetic Association Information Network)
Framingham SHARe – first two generations
NIDDK GoKinD and EDIC
Summer 2007
Framingham SHARe – third generation
Late Early 2008
GEI (Genes and Environment Initiative)
Features
Search analysis results by:
Gene
SNP or microsatellite marker
Genomic region
Filter analysis results by:
P-value
HWE
Minor allele frequency
Call rate?
Download
Public summaries
Authorized access for individual-level data
Other associations with phenotype (expression data..)

18. Acknowledgements Phenotype Genotype XML Authorized Access
Rinat Bagoutdinov
Luning Hao
Mas Kimura
Jimmy Jin
Natasha Popova
Stephanie Pretels
Karl Sirotkin
Jack Wang
Matt Mailman
Genotype
Mike Feolo
Lon Phan
David Shao
Ming Ward
Steve Sherry
XML
Kim Tryka
Laura Kelly
Jeff Beck
Authorized Access
Steve Sherry
Eugene Yaschenko
Valdimir Soussov
Misha Kimmelman
Don Preuss
Al Graeff
Jim Ostell

19. Document HTML

20. Document PDF

21. Multiple maps can be displayed to elucidate what is already known in
a particular genomic region