Dosage Sensitivity
The purpose of this page is to outline the main pages and core features each page contains. THIS IS A TEST - From Local
Table of contents
The Dosage Sensitivity Curation List acts the primary page for summary information about Dosage's curations to be listed. This page will support the ability to do the following...
- Provide visitors key summary facts about curations
- List all of the curations
- Provide a paginated list of all of the curations
- Allow visitors to "search" and "filter" Dosage curations
- Provide visitors ways to "sort" curations (all or matched)
- Provide helpful insights about other ClinGen curation activities
- Provide information from external resources to assist visitors
The curation totals are displayed in a few areas. On this page, figures displayed are totals for all of the curations done by dosage, regardless of filter, sort, or pagination configuration.
This page is seeking the following data to be returned to allow the totals to be displayed.
NOTE: JSON structure, key, and labels are intended to facilitate the discussion. Final structure and examples will be replace the options below.
Option 1 (For consideration)
This option has the API return the total curations along with totals based on each type of curation.
{
"curation-totals": {
"total": "1000",
"types": {
"genes": "500",
"regions": "500"
}
}
}
Option 2 (For consideration)
This option has the API return the totals based on each type of curation. The website will then take the data from the API to compute the total.
{
"curation-totals": {
"genes": "500",
"regions": "500"
}
}
This area of the user experience provide visitors with three key features
- The ability to see the filter that was set (Teal badge)
- The quick ability to remove a filter [x]
- The number of results matched (4)
- Click and expand the filter area to see all of the possible features (3)
NOTE: At this time (Oct 1, 2019) the filter capabilities are available. This area of the documentation TDB on how it will interact with the API.
Items to consider
- The UX should be retain what the user input in the filter and thus was sent to the API
- The API should return the filters that were used along with the results. This ensures the the UX display reflects the filters the API used. If filters were not used or not available the UX would be able to info the user and log the discrepancy for review.
This block (column) informs the visitor the gene or region that the curation was performed for. This is the most important data to be displayed.
Option 1 (For consideration)
This option has the API return the total curations along with totals based on each type of curation.
{
"curation": {
"gene": {
"label": "ABC123",
"curie": "HGNC:1234"
},
"iri": "unique123-4567"
}
}
| KEY | DESCRIPTION |
|---|---|
| curation | Placeholder - intended to provide context for the example |
| curation > gene | They key informs the UX what type of curation |
| curation > gene > label | The label that will be used on the row. For a gene this will be the gene symbol. The DCI provides a label but the API should provide the label (gene symbol) that HGNC provides (which the curation should be linked) |
| curation > gene > curie | The compact identifier for the gene (in this case). For a gene this should be HGNC:XXXX |
| curation > iri | The IRI to the specific curation. This IRI should be a permanent IRI and not subject to change if the database reset/rebuilt |
{
"curation": {
"region": {
"label": "6p12 region (includes ABC123)",
"curie": "6:157099063-157531913",
"build": {
"GRCH37": "6:157099063-157531913",
"GRCH38": "6:157090063-157501913"
}
},
"iri": "unique321-4567"
}
| KEY | DESCRIPTION |
|---|---|
| curation | Placeholder - intended to provide context for the example |
| curation > region | They key informs the UX what type of curation |
| curation > region > label | The label that will be used on the row. The DCI provides a label which the curator manually typed in. This is why some labels may have () or other special characters |
| curation > region > curie | For a region this would be the genome build that is being prioritized. This will be build (TBD GRCh37 or GRCh38) |
| curation > region > build | Including the build values allows the UX to provide additional display options. |
| curation > region > build > GRCH37 | The key informs the build and the value provides the coordinates |
| curation > region > build > GRCH38 | The key informs the build and the value provides the coordinates |
| curation > iri | The IRI to the specific curation. This IRI should be a permanent IRI and not subject to change if the database reset/rebuilt |
Sort Options This column will have sort abilities. The API should be able to accept a request to sort/re-sort the results. The UX should have the ability to pass the field (key) and the type of sort (ascending or descending).
- Sort by row 'label' (gene or region) in an ascending order
- Sort by row 'label' (gene or region) in an descending order
Over 17,000 protein coding genes have been scored according to their predicted probability of exhibiting haploinsufficiency. These predictions are generated using a classification model trained on two datasets:
- known haploinsufficient genes and
- genes disrupted by unambiguous loss-of-function variants in at least two apparently healthy individuals. The model uses sequence conservation, expression patterns and proximity within a gene network to known haploinsufficient genes as predictor variables. Missing predictor variables are imputed using other gene properties before prediction. Percentages refer to genome-wide percentiles of genes ranked according to their haploinsufficient score.
- High ranks (e.g. 0-10%) indicate a gene is more likely to exhibit haploinsufficiency, low ranks (e.g. 90-100%) indicate a gene is more likely to NOT exhibit haploinsufficiency.
- The manuscript describing the generation and validation of these haploinsufficiency predictions (Huang et al) is published in PLoS Genetics. Updated predictions of haploinsufficiency can be downloaded from our data download page. https://decipher.sanger.ac.uk/about#downloads/data
The Exome Aggregation Consortium (ExAC) has computed a score called pLI, which indicates the probability that a gene is intolerant to a Loss of Function (LoF) mutation. This analysis is based on high-quality exome sequence data for 60,706 individuals of diverse ethnicities.
The ExAC consortium used a selection-neutral, sequence-context-based mutational model to compare the observed number of rare variants per gene to an expected number, then quantified deviation from expectation with a Z score (method described in Samocha et al.). To reduce confounding by coding sequence length, for Protein Truncating Variants (PTV) an expectation-maximization algorithm using the observed and expected PTV counts within each gene was used to separate genes into three categories:
- Null, where observed ≈ expected (LoF variation is tolerated)
- Recessive, where observed ≤ 50% of expected (heterozygous LoFs are tolerated)
- Haploinsufficient, where observed < 10% of expected (heterozygous LoFs are not tolerated)
The pLI score is the probability that a given gene falls into the Haploinsufficient category, therefore is extremely intolerant of loss-of-function variation. Genes with high pLI scores (pLI ≥ 0.9) are extremely LoF intolerant, whereby genes with low pLI scores (pLI ≤ 0.1) are LoF tolerant.
The manuscript describing this dataset and analysis (Lek et al.) is published in Nature. http://exac.broadinstitute.org/
Views & Partials: Coming soon
- /resources/views/gene-dosage/show.blade.php
Coming soon Views & Partials:
- /resources/views/gene-dosage/show.blade.php
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Coming soon Views & Partials:
- /resources/views/gene-dosage/reports.blade.php
Coming soon Views & Partials:
- /resources/views/gene-dosage/stats.blade.php
Coming soon Views & Partials:
- /resources/views/gene-dosage/downloads.blade.php