database of Genotype and Phenotype http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap Kim Pruitt (for Matt Mailman) NCBI

Overview Phenotype Genotype Genotype X Phenotype Association

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’

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!

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?

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

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

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

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

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

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

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

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

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

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

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

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 2007- 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..)

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 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gap

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