Initial commit

README.md

+# Disease associations
+
+`Disease associations` is a plugin allowing one to see genes associated with given disease
+in the context of selected disease map. Currently, the plugin shows genes associations obtained
+from [Protein API variation service](https://www.ebi.ac.uk/proteins/api/doc/) (includes also
+information about specific variants)
+ and [Open Targets API](https://docs.targetvalidation.org/tutorials/rest-api).
+ 
+
+
+### General instructions
+
+In order to use the precompiled and publicly available version of the plugin, 
+open the plugin menu in the MINERVA's upper left corner (see image below) and click plugins.
+In the dialog which appears enter the following address in the URL box: `https://minerva-dev.lcsb.uni.lu/plugins/disease-associations/plugin.js` .
+The plugin shows up in the plugins panel on the right hand side of the screen.
+
+### Plugin functionality
+
+#### Obtaining disease-gene associations
+
+- The users picks whether she wants to input disease based on [EFO](https://www.ebi.ac.uk/efo/) ontology 
+or [OMIM](https://www.omim.org/) ontology (see 
+[Variation information data source section](#Variation-information)
+for details).
+- In case EFO is selected, when the users starts 
+inputting the disease of interest in the disease input box the plugin 
+starts suggesting available diseases from the [EFO ontology](https://www.ebi.ac.uk/efo/) 
+via the [EBI's ontology lookup service](https://www.ebi.ac.uk/ols/docs/api)
+- After a disease is selected, the plugin shows details of the disease including its
+synonyms and mapped [OMIM](https://www.omim.org/) ontology terms.
+- In case OMIM is selected, the user needs to input OMIM ID and no additional details 
+are shown.
+- After clicking on the <i>Retrieve</i> button,  
+the plugin connects to the [Protein API variation service](https://www.ebi.ac.uk/proteins/api/doc/) 
+and [Open Targets API](https://docs.targetvalidation.org/tutorials/rest-api) 
+and retrieves all available disease-gene associations. In case of Protein API, the associations are 
+based on the OMIM while in case of Open Targets, the associations are based directly on 
+the EFO ID which was used to provide the disease details.
+
+#### Disease-gene associations inspection
+
+The obtained associations are shown in tabs based on the the source of information.
+
+##### 1. Variation information from Protein API variation service
+
+The variation service is used to obtain disease-associated variants retrieved from large-scale
+genomics projects (see details in the respective section below).
+
+- Returned variants are grouped by isoforms of genes they are involved in. 
+The plugin groups variants in isoforms by gene name
+and displays them in a table where each row contains the gene name, number of occurrences of that gene in
+the map and number of isoforms.
+- The user can click on the eye icon of a particular gene to show its occurrences in the map. 
+If there is no occurrence of given gene in the map, 
+the number of occurrences is zero and no eye icon is displayed.
+- By clicking on the plus symbol in each line line, one can explore all the data which was obtained from 
+the Protein API for that gene. 
+
+##### 2. Associations from Open Targets
+
+Open Targets platform is used to obtain disease-gene associations including 
+an [aggregated association score](https://docs.targetvalidation.org/getting-started/scoring) showing the 
+strength of the respective association. Only associations with score > 0.2 are retrieved and displayed.
+
+- Each association contains the involved gene, strength of the association and link to Open Targets
+where one can inspect detailed information about the particular association.
+- The user can click on the eye icon of a particular gene to show its occurrences in the map. 
+If there is no occurrence of given gene in the map, no eye icon is displayed.
+
+
+### Data resources
+
+### Ontology Lookup Service (OLS)
+
+EBI's [OLS](https://www.ebi.ac.uk/ols/index) is used to obtain disease 
+[suggestions](https://www.ebi.ac.uk/ols/docs/api#_suggest_term) and
+[disease details]((https://www.ebi.ac.uk/ols/docs/api#resources-term)) from the
+[EFO ontology]((https://www.ebi.ac.uk/efo/)), one of the ontologies under the OLS umbrella.
+
+
+###Variation information
+
+The information about variants comes from EBI's [Proteins API](https://www.ebi.ac.uk/proteins/api/doc/#!/variation/search).
+As stated on the pages of Proteins API *"The variation, proteomics and antigen services 
+provide annotations imported and mapped from large scale data sources, 
+such as 1000 Genomes, ExAC (Exome Aggregation Consortium), 
+TCGA (The Cancer Genome Atlas), COSMIC (Catalogue Of Somatic Mutations In Cancer), 
+PeptideAtlas, MaxQB (MaxQuant DataBase), EPD (Encyclopedia of Proteome Dynamics) and HPA, 
+along with UniProtKB annotations for these feature types (if applicable)"*. 
+
+To specify the disease of interest, the Proteins API can be passed either a text or list of
+[OMIM](https://www.omim.org) identifiers. The plugin uses the latter option since 
+the EFO ontology includes also a mapping from EFO to OMIM. For example, 
+[Parkinson's disease](https://www.ebi.ac.uk/ols/ontologies/efo/terms?iri=http%3A%2F%2Fwww.ebi.ac.uk%2Fefo%2FEFO_0002508)
+is mapped to OMIM:616710, OMIM:616361, OMIM:168600. We should mention here that 
+OMIM ontology seems to have a more granular distinction of diseases and thus for example
+it contains Parkinson disease 1-10 which do not have exact mapping in EFO.  
+
+The following image shows an example of the data (a snippet from Google Chrome DevTools) 
+already grouped by gene name and species information (see above).
+
+![Grouped Proteins API data](img/data_example.png)
+
+### Open Targets
+
+Open Targets platform supports workflows starting 
+from a target or disease, and shows the available evidence for target – disease associations. 
+The plugin uses the [Open Targets Platform REST-API](https://docs.targetvalidation.org/tutorials/rest-api)
+to obtain the associations and their scores.
\ No newline at end of file

package.json

+{
+  "name": "disease-associations",
+  "version": "1.0.0",
+  "description": "",
+  "main": "index.js",
+  "scripts": {
+    "build-css": "node-sass --include-path src/css src/css/styles.scss src/css/styles.css",
+    "build": "mkdirp dist && npm run build-css && browserify -t [ babelify --presets es2015 ] -t browserify-css src/js/index.js | uglifyjs --compress --mangle > dist/plugin.js ",
+    "build-debug": "mkdirp dist && npm run build-css && browserify -t [ babelify --presets es2015 ] -t browserify-css src/js/index.js> dist/plugin.js ",
+    "watch-js": "mkdirp dist && npm run build-css && watchify -v -t [ babelify --presets es2015 ] -t browserify-css src/js/index.js -o dist/plugin.js",
+    "clean": "rimraf dist"
+  },
+  "author": "David Hoksza",
+  "license": "MIT",
+  "devDependencies": {
+    "babel-core": "^6.26.0",
+    "babel-preset-es2015": "^6.24.1",
+    "babelify": "^8.0.0",
+    "bower": "^1.5.2",
+    "browserify": "^14.5.0",
+    "browserify-css": "^0.13.1",
+    "mkdirp": "^0.5.1",
+    "node-sass": "^4.6.1",
+    "rimraf": "latest",
+    "uglify-js": "^3.1.9",
+    "watchify": "^3.9.0"
+  },
+  "dependencies": {
+    "bootstrap-table": "^1.12.1",
+    "bootstrap-treeview": "github:diegokogan/bootstrap-treeview",
+    "html-linkify": "^1.2.2",
+    "typeahead.js": "^0.11.1"
+  }
+}

src/css/styles.css

+@import url(../../node_modules/bootstrap-table/dist/bootstrap-table.min.css);
+.disease-associations-container {
+  padding: 15px; }
+
+.disease-associations-container .btn-search {
+  margin-bottom: 10px; }
+
+.disease-associations-container .input-disease {
+  text-align: center;
+  font-weight: bold;
+  width: 100%;
+  padding: 0; }
+
+.disease-associations-container .disease-submission .panel-heading {
+  padding: 3px 15px;
+  font-weight: bold;
+  cursor: pointer; }
+
+.disease-associations-container .associations-content .error-panel {
+  margin-top: 10px; }
+
+.disease-associations-container .disease-info {
+  padding: 3px; }
+
+.disease-associations-container .disease-info-label {
+  font-weight: bold; }
+
+.disease-associations-container .twitter-typeahead {
+  width: 100%; }
+
+.disease-associations-container .twitter-typeahead .tt-menu {
+  width: 100%; }
+
+.disease-associations-container .variation-table .glyphicon-eye-open {
+  cursor: pointer; }
+
+.disease-associations-container .opentargets-table .glyphicon-eye-open {
+  cursor: pointer; }
+
+.disease-associations-container .fixed-table-body {
+  overflow: auto; }
+
+.disease-associations-container .genes-loading {
+  text-align: center; }
+
+.disease-associations-container .genes-loading .fa-spin {
+  margin-right: 10px; }
+
+.disease-associations-container .btn-default.btn-on.active {
+  background-color: #5BB75B;
+  color: white; }
+
+.disease-associations-container .btn-default.btn-off.active {
+  background-color: #5BB75B;
+  color: white; }

src/css/styles.scss

+@import "../../node_modules/bootstrap-table/dist/bootstrap-table.min.css";
+
+$pluginName: disease-associations;
+
+.#{$pluginName}-container {
+  padding: 15px;
+}
+
+.#{$pluginName}-container .btn-search {
+  margin-bottom: 10px;
+}
+
+.#{$pluginName}-container .input-disease {
+  text-align: center;
+  font-weight: bold;
+  width: 100%;
+  padding: 0;
+}
+
+.#{$pluginName}-container .disease-submission .panel-heading {
+  padding: 3px 15px;
+  font-weight: bold;
+  cursor: pointer;
+  //background: rgba(0, 0, 0, 0.1);
+
+}
+
+//.#{$pluginName}-container .disease-submission .chevron:after {
+//  content: "\f078";
+//}
+//.#{$pluginName}-container .disease-submission.collapsed .chevron:after {
+//  content: "\f054";
+//}
+
+.#{$pluginName}-container .associations-content .error-panel{
+  margin-top: 10px;
+}
+
+.#{$pluginName}-container .disease-infos {
+  //padding: 3px 0px;
+  //background: rgba(1, 1, 1, 0.1);
+  //border-radius: 5px;
+}
+
+
+.#{$pluginName}-container .disease-info {
+  padding: 3px;
+}
+
+.#{$pluginName}-container .disease-info-label {
+  font-weight: bold;
+}
+
+
+.#{$pluginName}-container .twitter-typeahead {
+  width: 100%;
+}
+
+.#{$pluginName}-container .twitter-typeahead .tt-menu{
+  width: 100%;
+}
+
+
+
+.#{$pluginName}-container .variation-table .glyphicon-eye-open {
+  cursor: pointer;
+}
+
+.#{$pluginName}-container .opentargets-table .glyphicon-eye-open {
+  cursor: pointer;
+}
+
+.#{$pluginName}-container .fixed-table-body {
+  overflow: auto;
+}
+
+.#{$pluginName}-container .genes-loading {
+  text-align: center;
+}
+
+.#{$pluginName}-container .genes-loading .fa-spin{
+  margin-right: 10px;
+}
+
+
+.#{$pluginName}-container .btn-default.btn-on.active{background-color: #5BB75B;color: white;}
+.#{$pluginName}-container .btn-default.btn-off.active{background-color: #5BB75B ;color: white;}
\ No newline at end of file

src/js/ols.js

+const getDisease = function(iri){
+
+    const encodedIri = encodeURIComponent(encodeURIComponent(iri));
+
+    return $.ajax({
+        url: `https://www.ebi.ac.uk/ols/api/ontologies/efo/terms/${encodedIri}`
+    });
+};
+
+const suggestDiseases = function (text) {
+
+    let suggestedDisDesc = []; //array of suggestion-disease description pair
+
+    return $.ajax({
+        url: `https://www.ebi.ac.uk/ols/api/suggest?q=${encodeURIComponent(text)}&ontology=efo&rows=20`
+    }).then(function (res) {
+        const suggestions = res.response.docs.map(d => {
+            suggestedDisDesc.push({suggestion: d.autosuggest, desc: undefined});
+            return d.autosuggest;
+        });
+        const promises =  suggestions.map(s => $.ajax({url: `https://www.ebi.ac.uk/ols/api/search?q=${encodeURIComponent(s)}&ontology=efo&queryFields=label,synonym&exact=true`}))
+        return Promise.all(promises);
+    }).then(function (ress) {
+
+        for (let i = ress.length -1; i >=0; i--) {
+            const res = ress[i];
+            if (res.response.docs.length > 0 && 'obo_id' in res.response.docs[0]) {
+                suggestedDisDesc[i].desc = res.response.docs[0];
+            } else {
+                suggestedDisDesc.splice(i, 1);
+            }
+        }
+
+        const promises = suggestedDisDesc
+            .map(sdd => $.ajax({url: `https://www.ebi.ac.uk/ols/api/ontologies/efo/ancestors?id=${encodeURIComponent(sdd.desc.obo_id)}`}));
+
+        return Promise.all(promises);
+
+    }).then(function (ress) {
+
+        const sd = {};
+
+        suggestedDisDesc.forEach(function (sdd, i) {
+            if (ancestorsContainDisease(ress[i])) {
+                sd[sdd.suggestion] = sdd.desc;
+            }
+        });
+
+        return sd;
+    })
+};
+
+const ancestorsContainDisease = function(ancestorsJson) {
+
+    let isDisease = false;
+    ancestorsJson._embedded.terms.forEach(t => isDisease = isDisease || (t.obo_id === "EFO:0000408"));
+    return isDisease;
+};
+
+module.exports = {
+    suggestDiseases: suggestDiseases
+    , getDisease: getDisease
+};
\ No newline at end of file