Wiki » History » Version 63
Jason Bobe, 03/09/2010 10:33 PM
Splitting Clinical Impact out
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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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 | 63 | Jason Bobe | Each of these fields is a sliding scale of 0-5 where 0 represents no evidence and 5 strong evidence within the given category. 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 | 58 | Jason Bobe | a. Computational: 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 | 44 | Jason Bobe | i. NBLOSUM >= 2 |
28 | 27 | Jason Bobe | i. GVGD |
29 | 23 | Jason Bobe | i. Other variants in this gene cause similar disease |
30 | i. etc... |
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31 | 58 | Jason Bobe | a. Functional: One star for each experiment supporting the result, and penalize one star for conflicting results from: |
32 | 23 | Jason Bobe | i. enzyme extracts |
33 | i. cell lines |
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34 | i. animal models |
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35 | i. etc... |
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36 | 50 | Jason Bobe | 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 |
37 | 40 | Jason Bobe | i. 0 stars if no higher ranking is allowed |
38 | 41 | Jason Bobe | i. 1 star if OR>1 and significance <= 0.1 |
39 | i. 2 stars if OR>=1.5 and significance <= 0.05 |
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40 | 45 | Jason Bobe | i. 3 stars if OR>=2 and significance <= 0.025 |
41 | i. 4 stars if OR>=3 and significance <= 0.01 |
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42 | i. 5 stars if OR>=5 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 | 1 | Jason Bobe | i. 5 stars for LOD > 3 |
50 | 63 | Jason Bobe | |
51 | === Clinical Impact === |
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52 | As with the Variant Quality section, each of these fields is a sliding scale of 0-5. These two categories are not applicable for benign and protective variants. |
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53 | |||
54 | 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). For pharmacogenetic variants this is the severity of using the wrong drug/dosage. |
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55 | 51 | Jason Bobe | i. 0 stars for benign |
56 | 60 | Jason Bobe | i. 1 star for very low expectation of having symptoms for this genotype, very low penetrance (eg. Susceptibility to crohn's with OR = 4.5, causing a ~.2% risk of Crohn's) |
57 | i. 2 stars for mild effect on quality of life or unlikely to be symptomatic (Cystinuria) |
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58 | i. 3 stars for moderate effect on quality of life (eg. Familial mediterranean fever) |
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59 | i. 4 stars for severe effect: causes serious disability or reduces life expectancy (eg. Sickle-cell, Stargardt's disease) |
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60 | i. 5 stars for very severe effect: early lethal (eg. Familial adenomatous polypopsis, adrenoleukodystrophy) |
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61 | 51 | Jason Bobe | a. Treatability: |
62 | i. 0 stars for no clinical evidence supporting intervention (eg. PAF acetylhydrolase deficiency) |
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63 | i. 1 star for uncurable: treatment only to alleviate symptoms (eg. adrenoleukodystrophy) |
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64 | 59 | Jason Bobe | i. 2 stars for potentially treatable: Treatment is in development or controversial |
65 | i. 3 stars for treatable but a significant fraction do not require treatment (Cystinuria) |
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66 | 1 | Jason Bobe | i. 4 stars for treatable: Standard treatment reduces the amount of mortality/morbidity but does not eliminate it (eg. Sickle-cell disease) |
67 | 54 | Jason Bobe | i. 5 stars for extremely treatable: Well-established treatment essentially eliminates the effect of the disease (eg. PKU) |
68 | 47 | Jason Bobe | |
69 | 63 | Jason Bobe | === Impact === |
70 | 32 | Jason Bobe | a. Pathogenic: Causative for disease. |
71 | a. Benign: No clinically significant phenotype. |
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72 | 1 | Jason Bobe | a. Protective: Protective from disease. |
73 | a. Pharmacogenetic: Clinically significant phenotype in the presence of a pharmacological agent. |
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74 | 43 | Jason Bobe | a. NR: Not reviewed. |
75 | 34 | Jason Bobe | |
76 | 56 | Jason Bobe | In addition to these impacts, qualifiers will be added according to the variant quality information (ie. the stars). |
77 | |||
78 | 61 | Jason Bobe | For pathogenic and pharmacogenetic: |
79 | a. (no qualifier given): at least 4 stars in one of the human evidence categories (case/control or familial), at least 4 stars in one of the clinical categories (severity or treatability), and at least 12 stars total. |
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80 | 56 | Jason Bobe | a. "likely": at least 3 stars in one of the human evidence categories, at least 3 stars in one of the clinical categories, and at least 10 stars total. |
81 | a. "uncertain": all the rest. |
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82 | |||
83 | 62 | Jason Bobe | For benign and protective variants, severity and treatibility should be regarded as not applicable (NA) and not counted: |
84 | 61 | Jason Bobe | a. (no qualifier given): at least 4 stars in one of the human evidence categories, and at least 8 stars total. |
85 | 56 | Jason Bobe | a. "likely": at least 3 stars in one of the human evidence categories, and at least 6 stars total. |
86 | a. "uncertain": all the rest. |
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87 | 39 | Jason Bobe | |
88 | 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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89 | 19 | Jason Bobe | |
90 | === Inheritance Pattern === |
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91 | a. Dominant |
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92 | a. Recessive |
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93 | 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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94 | a. Undefined: Undefined in the literature. |
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95 | a. Unknown: The default value for all variants and all variants without literature. |
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96 | |||
97 | === Summary of published research, and additional commentary === |
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98 | 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. |
99 | 1 | Jason Bobe | |
100 | 21 | Jason Bobe | === Allele Frequency === |
101 | 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. |
102 | 21 | Jason Bobe | |
103 | === Publications === |
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104 | |||
105 | * 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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106 | |||
107 | === Genomes === |
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108 | |||
109 | * 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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110 | |||
111 | === Other External References === |
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112 | These are automatically generated by web "robots": |
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113 | 13 | Jason Bobe | a. dbSNP: The link to the dbSNP entry for this nucleotide position (for this nucleotide change?) |
114 | 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. |
115 | a. Web Search Results: A web search for this exact variant using the Yahoo search engine |
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116 | 21 | Jason Bobe | |
117 | === Edit History === |
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118 | * Automatically generated history of all page edits with the contributor's name. |
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119 | 20 | Jason Bobe | |
120 | == To Do == |
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121 | * [wiki:GET-Evidence/23andWe] |
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122 | 3 | Jason Bobe | |
123 | 1 | Jason Bobe | == Suggestions == |
124 | |||
125 | * your suggestion here. |