Wiki » History » Version 40
Jason Bobe, 02/23/2010 08:26 PM
amending case/control criteria
1 | 36 | Jason Bobe | = Genotype + Environment = Trait Evidence (GET-E) Database = |
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2 | 1 | Jason Bobe | |
3 | 38 | Jason Bobe | 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]. |
4 | 1 | Jason Bobe | |
5 | You can find the PGP production server at: |
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6 | * http://evidence.personalgenomes.org |
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7 | |||
8 | A development sandbox can be found at: |
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9 | * http://evidence-dev.personalgenomes.org |
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10 | |||
11 | 37 | Jason Bobe | Many contributors helped make '''GET-E''' possible. You can find specific contributions at: |
12 | 1 | Jason Bobe | * http://evidence.personalgenomes.org/editors |
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14 | 38 | Jason Bobe | 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! |
15 | 1 | Jason Bobe | |
16 | 28 | Jason Bobe | == Field Descriptions and Editing Guidelines == |
17 | 19 | Jason Bobe | === Short Summary === |
18 | * free text providing a one line summary of clinical action to be undertaken given this variant (possibly modified by known phenotypes). |
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19 | |||
20 | 23 | Jason Bobe | === Variant Quality Data === |
21 | 1 | Jason Bobe | 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 |
22 | 35 | Jason Bobe | a. ''In silico'': One star for each consistent prediction and one star subtracted for conflicting results from: |
23 | 26 | Jason Bobe | i. evolutionary conservation (minimum of three species) |
24 | i. presence in active domain |
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25 | 27 | Jason Bobe | i. SIFT |
26 | i. !PolyPhen |
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27 | i. NBLOSUM |
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28 | i. GVGD |
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29 | 23 | Jason Bobe | i. Other variants in this gene cause similar disease |
30 | i. etc... |
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31 | a. ''In vitro'': One star for each experiment supporting the result, and penalize one star for conflicting results from: |
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32 | i. enzyme extracts |
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33 | i. cell lines |
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34 | i. animal models |
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35 | i. etc... |
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36 | 24 | Jason Bobe | a. Case/Control: Odds Ratio etc... |
37 | 40 | Jason Bobe | i. 0 stars if no higher ranking is allowed |
38 | i. 1 star if OR>1 and significance >= 0.1 |
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39 | i. 2 stars if OR>=1.5 and significance >= 0.05 |
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40 | i. 3 stars if OR>=3 and significance >= 0.025 |
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41 | i. 4 stars if OR>=10 and significance >= 0.01 |
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42 | i. 5 stars if OR>=30 and significance >= 0.0001 |
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43 | 24 | Jason Bobe | a. Familial Disease Segregation |
44 | 25 | Jason Bobe | i. 0 stars for no segregation (LOD < -2) |
45 | 24 | Jason Bobe | i. 1 star if segregation exists in one family pedigree |
46 | 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) |
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47 | i. 3 stars for more than one family no conflicting information |
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48 | i. 4 stars for LOD > 2 |
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49 | i. 5 stars for LOD > 3. |
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50 | 1 | Jason Bobe | a. Clinical Outcomes: The quality of studies investigating the effectiveness of action based on the described impact of this mutation given a specific phenotype/family history |
51 | 25 | Jason Bobe | i. 0 stars for poor outcome for intervention (diagnostic and medical) |
52 | i. 1 star no proven benefit for intervention |
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53 | i. 2 stars anecdotal evidence for intervention (unpublished results) |
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54 | i. 3 stars weak evidence for intervention (less than 10 cases) |
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55 | i. 4 stars standard recommendations for further intervention in development (or more than 10 cases) |
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56 | i. 5 stars for further intervention in routine use |
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57 | |||
58 | 19 | Jason Bobe | === Impact === |
59 | 32 | Jason Bobe | a. Pathogenic: Causative for disease. |
60 | a. Benign: No clinically significant phenotype. |
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61 | 1 | Jason Bobe | a. Protective: Protective from disease. |
62 | a. Pharmacogenetic: Clinically significant phenotype in the presence of a pharmacological agent. |
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63 | 39 | Jason Bobe | a. NA: Not yet reviewed. |
64 | 34 | Jason Bobe | |
65 | 39 | Jason Bobe | In addition to these impacts, qualifiers will be added according to the variant quality information (ie. the stars). 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). |
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67 | 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. |
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68 | 19 | Jason Bobe | |
69 | === Inheritance Pattern === |
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70 | a. Dominant |
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71 | a. Recessive |
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72 | 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. |
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73 | a. Undefined: Undefined in the literature. |
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74 | a. Unknown: The default value for all variants and all variants without literature. |
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75 | |||
76 | === Summary of published research, and additional commentary === |
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77 | 22 | Jason Bobe | * Free text providing a comprehensive review of the variant including youngest age of onset, oldest age of onset and oldest asymptomatic individual. |
78 | 1 | Jason Bobe | |
79 | 21 | Jason Bobe | === Allele Frequency === |
80 | 22 | Jason Bobe | * 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. |
81 | 21 | Jason Bobe | |
82 | === Publications === |
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83 | |||
84 | * 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). |
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85 | |||
86 | === Genomes === |
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87 | |||
88 | * 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. |
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89 | |||
90 | === Other External References === |
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91 | These are automatically generated by web "robots": |
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92 | 13 | Jason Bobe | a. dbSNP: The link to the dbSNP entry for this nucleotide position (for this nucleotide change?) |
93 | 12 | Jason Bobe | a. Genetests: Link to all clinical laboratories performing diagnostic tests on this gene and the list of diseases that the labs are looking for. |
94 | a. Web Search Results: A web search for this exact variant using the Yahoo search engine |
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95 | 21 | Jason Bobe | |
96 | === Edit History === |
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97 | * Automatically generated history of all page edits with the contributor's name. |
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98 | 20 | Jason Bobe | |
99 | == To Do == |
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100 | * [wiki:GET-Evidence/23andWe] |
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101 | 3 | Jason Bobe | |
102 | 1 | Jason Bobe | == Suggestions == |
103 | |||
104 | * your suggestion here. |