GET-Evidence

= Genotype + Environment = Trait Evidence (GET-E) Database =

The '''GET-E''' project was started by Abraham Rosenbaum, Joe Thakuria, Xiaodi Wu and Alexander Wait Zaranek to help the [http://personalgenomes.org Personal Genome Project], the clinical genetics community, and, the general public interpret individual genomes. The database is closely integrated with [wiki:Trait-o-matic].

You can find the PGP production server at: * http://evidence.personalgenomes.org

A development sandbox can be found at: * http://evidence-dev.personalgenomes.org

Many contributors helped make '''GET-E''' possible. You can find specific contributions at: * http://evidence.personalgenomes.org/editors

Please help the project by editing the database, writing software tools that use the database (eg. Trait-o-matic/AETAS) or by making suggestions on the wiki!

Field Descriptions and Editing Guidelines === Short Summary === * free text providing a one line summary of clinical action to be undertaken given this variant (possibly modified by known phenotypes).

=== Variant Quality Data === 
Each of these fields is a sliding scale of 0-5 where 0 represents no evidence and 5 strong evidence that the Impact is correct. Where the data is not entered the default is N/A. When Genetests and/or the literature correlate this variant with a number of phenotypes the impact should be reported for the most extreme condition
 a. ''In silico'': One star for each consistent prediction and one star subtracted for conflicting results from:
  i. evolutionary conservation (minimum of three species)
  i. presence in active domain 
  i. SIFT 
  i. !PolyPhen 
  i. NBLOSUM >= 2
  i. GVGD
  i. Other variants in this gene cause similar disease 
  i. etc... 
 a. ''In vitro'': One star for each experiment supporting the result, and penalize one star for conflicting results from: 
  i. enzyme extracts 
  i. cell lines  
  i. animal models
  i. etc... 
 a. Case/Control: A combination of odds ratio and significance test (currently using Fisher's Exact Test). For protective alleles, use inverse OR = 1 / OR. Do not count related individuals, count probands -- ie. one per family
  i. 0 stars if no higher ranking is allowed
  i. 1 star if OR>1 and significance <= 0.1
  i. 2 stars if OR>=1.5 and significance <= 0.05
  i. 3 stars if OR>=2 and significance <= 0.025
  i. 4 stars if OR>=3 and significance <= 0.01
  i. 5 stars if OR>=5 and significance <= 0.0001
 a. Familial Disease Segregation
  i. 0 stars for no segregation (LOD < -2)
  i. 1 star if segregation exists in one family pedigree
  i. 2 stars for segregation in more than one family with some conflicting information (e.g. asymptomatic carrier of young age or possibility of second causative mutation)
  i. 3 stars for more than one family no conflicting information
  i. 4 stars for LOD > 2
  i. 5 stars for LOD > 3
 a. Disease severity: downgraded according to disease penetrance (eg. Crohn's disease would be moderate or severe, but "increased susceptibility" is only increased the chances by ~.15% and so is called mild) 
  i. 0 stars for benign
  i. 1 star for very mild impact (eg. Alpha-1-antitrypsin deficiency)
  i. 2 stars for mild impact
  i. 3 stars for moderate impact (eg. Cystineria)
  i. 4 stars for severe impact: potentially lethal (eg. sickle-cell)
  i. 5 stars for very severe impact: lethal or severe damage (eg. Bardet-Biedl, PKU)
 a. Treata
 a. Treatability:
  i. 0 stars for no clinical evidence supporting intervention (eg. PAF acetylhydrolase deficiency)
  i. 1 star for uncurable: treatment only to alleviate symptoms (eg. Bardet-Biedl)
  i. 2 stars for potentially treatable: Treatment is in development or controversial
  i. 3 stars for treatable: Well-established treatment reduces the amount of mortality/morbidity but does not eliminate it (eg. Sickle-cell disease)
  i. 4 for very treatable: Well-established treatment greatly reduces the effect of the disease (eg. Cystinuria)
  i. 5 stars for extremely treatable: Well-established treatment effectively eliminates the effect of the disease (eg. PKU)

=== Impact === 
 a. Pathogenic: Causative for disease. 
 a. Benign: No clinically significant phenotype. 
 a. Protective: Protective from disease.
 a. Pharmacogenetic: Clinically significant phenotype in the presence of a pharmacological agent.    
 a. NR: Not reviewed.

In addition to these impacts, qualifiers will be added according to the variant quality information (ie. the stars). "Clinical outcome" score is treated as no higher than the maximum score of either "case/control" or "familial". The evidence must have at least four stars in any one of the clinical categories (case/control, familial, clinical outcomes) and at least ten stars total from all categories for the impact to be unqualified (ie. "pathogenic", "benign", "protective", or "pharmacogenetic"). The evidence must have three stars in any one of the clinical categories and at least six stars total from all categories for the impact to be qualified as "likely" (ie. "likely pathogenic", etc). All other impacts are qualified as "uncertain" (ie. "uncertain pathogenic", etc).

When Genetests and/or the literature give multiple phenotypes for a variant, the impact should be reported for the most extreme condition and annotated as such in the ''short summary''. In the future we hope to list different phenotypes separately.

=== Inheritance Pattern === 
 a. Dominant
 a. Recessive
 a. Other: A defined form of inheritance that is neither dominant or recessive (e.g. modifier, co-dominant, incomplete penetrance). These variants will get prioritized due to their potential phenotypic affect should the additional factors be present.
 a. Undefined: Undefined in the literature.
 a. Unknown: The default value for all variants and all variants without literature.

=== Summary of published research, and additional commentary ===

• Free text providing a comprehensive review of the variant including youngest age of onset, oldest age of onset and oldest asymptomatic individual.

=== Allele Frequency ===

• Automatically generated frequencies for the !HapMap Project, 1000 Genomes Project and the weighted average of the two. Sub-population frequencies and homozygous/heterozygous break-downs are currently not shown.

=== Publications ===

• User-entered publications and user entered synopses of the relevant details from the publication. A short summary is also entered for each paper (as above).

=== Genomes ===

• Automatically generated list of all genomes from Trait-o-matic in which this variant is seen. Additionally, specific actions taken by each individual harboring the variant can be reported.

=== Other External References === 
These are automatically generated by web "robots":  
   a. dbSNP: The link to the dbSNP entry for this nucleotide position (for this nucleotide change?)
   a. Genetests: Link to all clinical laboratories performing diagnostic tests on this gene and the list of diseases that the labs are looking for.
   a. Web Search Results: A web search for this exact variant using the Yahoo search engine

=== Edit History ===

• Automatically generated history of all page edits with the contributor's name.

To Do * [wiki:GET-Evidence/23andWe] Suggestions

• your suggestion here.