Hardcode for REVUE + Protein Override Annotations

.vscode/launch.json

@@ -0,0 +1,15 @@
+{
+    // Use IntelliSense to learn about possible attributes.
+    // Hover to view descriptions of existing attributes.
+    // For more information, visit: https://go.microsoft.com/fwlink/?linkid=830387
+    "version": "0.2.0",
+    "configurations": [
+        {
+            "type": "chrome",
+            "request": "launch",
+            "name": "Launch Chrome against localhost",
+            "url": "http://localhost:8080",
+            "webRoot": "${workspaceFolder}"
+        }
+    ]
+}

src/component/Header.tsx

@@ -58,6 +58,9 @@ class Header extends React.Component<{}> {
                                 <Nav.Link href="/news" className="ml-5">
                                     News
                                 </Nav.Link>
+                                {/* <Nav.Link href="/Revue" className="ml-5">
+                                    Revue
+                                </Nav.Link> */}
                             </Nav>
                         </Navbar.Collapse>
                     </Container>

src/component/variantPage/BasicInfo.tsx

@@ -20,6 +20,8 @@ import basicInfo from './BasicInfo.module.scss';
 import { Link } from 'react-router-dom';
 import { annotationQueryFields } from '../../config/configDefaults';
 import Toggle from '../Toggle';
+// importing revue eventually to check for entries and display VUE pill
+//import { default as jsonData } from '../../data/CuriousCasesList.json';
 
 interface IBasicInfoProps {
     annotation: VariantAnnotationSummary | undefined;
@@ -210,6 +212,7 @@ export default class BasicInfo extends React.Component<IBasicInfoProps> {
         if (transcript === undefined) {
             return null;
         }
+
         let parsedData: BasicInfoData[] = [];
         // gene
         parsedData.push({
@@ -235,18 +238,92 @@ export default class BasicInfo extends React.Component<IBasicInfoProps> {
             key: 'tsg',
             category: 'tsg',
         });
+
+        //REVUE blip for KIT variant based on transcript ID
+        if (transcript.transcriptId === 'ENST00000288135') {
+            parsedData.push({
+                value: 'VUE',
+                key: 'RevueAnnotation',
+                category: getMutationTypeClassName(transcript),
+            });
+        } else {
+            // variant classification
+            parsedData.push({
+                value: transcript.variantClassification,
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        }
+
+        // harcode for KIT protein change
+        if (transcript.transcriptId === 'ENST00000288135') {
+            parsedData.push({
+                value: 'p.549_557del',
+                key: 'hgvsShort',
+                category: 'default',
+            });
+        }
+
         // protein change
-        parsedData.push({
-            value: transcript.hgvspShort,
-            key: 'hgvsShort',
-            category: 'default',
-        });
-        // variant classification
-        parsedData.push({
-            value: transcript.variantClassification,
-            key: 'variantClassification',
-            category: getMutationTypeClassName(transcript),
-        });
+        else if (transcript.transcriptId !== 'ENST00000257430') {
+            parsedData.push({
+                value: transcript.hgvspShort,
+                key: 'hgvsShort',
+                category: 'default',
+            });
+        }
+
+        //hardcode for APC protein change
+        // if (transcript.transcriptId === 'ENST00000257430') {
+        //     parsedData.push({
+        //         value: 'Gly279Phefs*11',
+        //         key: 'hgvsShort',
+        //         category: 'default',
+        //     });
+        // }
+        // // protein change
+        // else {
+        //     parsedData.push({
+        //         value: transcript.hgvspShort,
+        //         key: 'hgvsShort',
+        //         category: 'default',
+        //     });
+        // }
+
+        //hardcode for KIT variant classification
+        if (transcript.transcriptId === 'ENST00000288135') {
+            parsedData.push({
+                value: 'In frame deletion',
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        } else if (transcript.transcriptId === 'ENST00000257430') {
+            parsedData.push({
+                value: 'Frameshift',
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        } else if (transcript.transcriptId === 'ENST00000460680') {
+            parsedData.push({
+                value: 'Exon Skipping',
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        } else if (transcript.transcriptId === 'ENST00000256078') {
+            parsedData.push({
+                value: 'Splice',
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        } else {
+            // variant classification
+            parsedData.push({
+                value: transcript.variantClassification,
+                key: 'variantClassification',
+                category: getMutationTypeClassName(transcript),
+            });
+        }
+
         // variant type
         parsedData.push({
             value: this.props.annotation!.variantType,

src/component/variantPage/biologicalFunction/CuriousCase.tsx

@@ -27,12 +27,32 @@ const TooltipLinks: React.FunctionComponent<{ pubmedIds: number[] }> = (
     return <>{tooltipLinks}</>;
 };
 
+// API pull
+// const CuriousCaseContent: React.FunctionComponent<{
+//     curiousCases?: CuriousCases;
+// }> = (props) => {
+//     return props.curiousCases ? (
+//         <span>
+//             {props.curiousCases.comment} {`. Pubmed ids: `}
+//             {props.curiousCases.pubmedIds ? (
+//                 <TooltipLinks pubmedIds={props.curiousCases.pubmedIds} />
+//             ) : (
+//                 'NA'
+//             )}
+//         </span>
+//     ) : (
+//         <span>NA</span>
+//     );
+// };
+
+// Hardcode version
 const CuriousCaseContent: React.FunctionComponent<{
     curiousCases?: CuriousCases;
 }> = (props) => {
     return props.curiousCases ? (
         <span>
-            {props.curiousCases.comment} {`. Pubmed ids: `}
+            {props.curiousCases.comment} <br />
+            {`Pubmed ids: `}
             {props.curiousCases.pubmedIds ? (
                 <TooltipLinks pubmedIds={props.curiousCases.pubmedIds} />
             ) : (
@@ -44,6 +64,24 @@ const CuriousCaseContent: React.FunctionComponent<{
     );
 };
 
+//Version to hardcode entire json
+// const CuriousCaseContent: React.FunctionComponent<{
+//     curiousCases?: CuriousCases;
+// }> = (props) => {
+//     return props.curiousCases ? (
+//         <span>
+//             {props.curiousCases.comment} {`. Pubmed ids: `}
+//             {props.curiousCases.pubmedIds ? (
+//                 <TooltipLinks pubmedIds={props.curiousCases.pubmedIds} />
+//             ) : (
+//                 'NA'
+//             )}
+//         </span>
+//     ) : (
+//         <span>NA</span>
+//     );
+// };
+
 @observer
 export default class CuriousCase extends React.Component<ICuriousCaseProps> {
     public render() {
@@ -54,11 +92,12 @@ export default class CuriousCase extends React.Component<ICuriousCaseProps> {
                         placement="top"
                         overlay={<div>Curated list of splice variants.</div>}
                     >
-                        <span
+                        {/* <span
                             className={functionalGroupsStyle['without-linkout']}
                         >
-                            Curious Case
-                        </span>
+                            reVUE
+                        </span> */}
+                        <a href={'https://www.cancerrevue.org/'}>reVUE</a>
                     </DefaultTooltip>
                 </div>
                 <CuriousCaseContent curiousCases={this.props.curiousCases} />

src/data/CuriousCasesList.json

@@ -0,0 +1,32 @@
+[
+    {
+        "hugoGeneSymbol": "APC",
+        "genomicLocation": "5:g.112151184A>G",
+        "comment": "Introduces splice acceptor site causing a frameshift",
+        "pubmedIds": [29316426]
+    },
+    {
+        "genomicLocation": "3:g.52439306A>G",
+        "comment": "Leads to exon 11 skipping, recurrent in prognostic and kidney cancer",
+        "pubmedIds": [33681728],
+        "hugoGeneSymbol": "BAP1"
+    },
+    {
+        "genomicLocation": "4:g.55593576_55593606del",
+        "comment": "In-frame deletion event at intron10-exon 11 boundary, commmon in Gastrointestinal Stromal Tumors. Revised Protein Annotation: p.549_557del",
+        "pubmedIds": [15507676, 27600498, 32697050],
+        "hugoGeneSymbol": "KIT"
+    },
+    {
+        "genomicLocation": "17:g.7579883G>A",
+        "comment": "Affects mRNA structure, reduces HDM2 binding, recurrent in many cancer types",
+        "pubmedIds": [31671760],
+        "hugoGeneSymbol": "TP53"
+    },
+    {
+        "genomicLocation": "12:g.25380277G>T",
+        "comment": "Introduces a splice donor site if Q61K is not co-occurring with G60G, recurrent in many cancer types",
+        "pubmedIds": [35236983],
+        "hugoGeneSymbol": "KRAS"
+    }
+]

src/page/Main.tsx

@@ -12,6 +12,7 @@ import { VariantStore } from './VariantStore';
 import { observer } from 'mobx-react';
 import News from './News';
 import { MainStore } from './MainStore';
+import Revue from './REVUEPage';
 
 @observer
 class Main extends React.Component<{}> {
@@ -56,6 +57,12 @@ class Main extends React.Component<{}> {
                                 component={Patient}
                             />
                             <Route exact={true} path="/news" component={News} />
+                            //adding revue
+                            <Route
+                                exact={true}
+                                path="/Revue"
+                                component={Revue}
+                            />
                             <Route exact={true} path="/api" component={Api} />
                         </Switch>
                     </div>

src/page/REVUEPage.tsx

@@ -0,0 +1,118 @@
+import * as React from 'react';
+//import { useTable } from 'react-table';
+//import { default as JsonData } from '../data/CuriousCasesList.json';
+
+import JsonDataDisplay from '../page/REVUETable';
+function App() {
+    return (
+        <div
+            className="App"
+            style={{
+                justifyContent: 'center',
+                alignItems: 'center',
+                height: '100vh',
+            }}
+        >
+            <h1>
+                reVUE: Repository for Variants with Unexpected Effects {'\n'}{' '}
+            </h1>
+
+            <p>
+                {' '}
+                {'\n'} Clinical sequencing of tumor samples has emerged as a
+                component of routine cancer care. By identifying genomic
+                alterations that contribute to tumor initiation or progression,
+                clinical sequencing may be used to identify predictive
+                biomarkers of drug response, refine patient cancer diagnoses,
+                assess heritable cancer risk, or inform patient prognosis. Most
+                genomic alterations are accurately annotated with tools such as
+                the Variant Effect Predictor (VEP) 1 that infer their effects on
+                the mRNA and protein by following basic rules of transcription,
+                mRNA post-transcriptional processing, and translation. For
+                example, most single nucleotide changes in coding regions of the
+                DNA lead to missense mutations, nonsense mutations, frameshift
+                insertions or deletions at the protein level, which may
+                hyperactivate or inactivate the protein. However, some genomic
+                variants are not as easily captured by these rules, which can
+                cause inappropriate or unclear annotation of the protein effect.
+                For example, a variant that alters an existing splice site or
+                creates a new one can inactivate or activate the protein. and,
+                similarly, specific mutations in the non-coding promoter region
+                of a gene may de-regulate gene expression. Collectively, we term
+                these variants “variants with unexpected effects (VUE)”. While
+                many of these are functionally characterized and documented in
+                the literature, there is currently no centralized database that
+                identifies, curates and programmatically stores these events,
+                enabling their annotation during routine clinical cancer genomic
+                sequencing. Certain VUEs may have therapeutic implications,
+                which, if mis-annotated may lead to suboptimal treatment
+                decisions for individual patients with cancer. For example,
+                in-frame KIT exon 11 deletions are recurrent in patients with
+                gastrointestinal stromal tumors (GIST) and are biomarkers for
+                the use of imatinib as first-line therapy. About 2-3% of GIST
+                tumors harbor KIT exon 11 deletions that extend into the
+                non-coding intron between exons 10 and 11. Although these events
+                have been shown to cause in-frame deletions, they are typically
+                misclassified as inactivating splice site mutations, precluding
+                patients carrying these mutations from receiving standard care
+                imatinib. To address this unmet clinical need, we propose to
+                build a novel bioinformatic application, REVUE, a REpository for
+                Variants with Unexpected Effect. The application will curate and
+                store all VUE relevant information, be freely accessible via an
+                intuitive website and through an application programming
+                interface (API), and will accept feedback and submission of new
+                VUEs from the cancer genomics community. It will be an important
+                resource for clinical bioinformatic pipelines to accurately
+                annotate all DNA mutations, with important implications for the
+                subset of patients with cancers harboring VUEs. {'\n'}
+            </p>
+            <JsonDataDisplay />
+        </div>
+    );
+}
+
+export default App;
+// class Revue extends React.Component<{}> {
+//     public render() {
+//         return (
+//             <React.Fragment>
+//                 <p>REVUE page is under construction.</p>
+//             </React.Fragment>
+//         );
+//     }
+// }
+
+// class Revue extends React.Component<{}> {
+//     public render() {
+//         return (
+//             function JsonDataDisplay() {
+//                 const DisplayData = JsonData.map((info) => {
+//                     return (
+//                         <tr>
+//                             <td>{info.hugoGeneSymbol}</td>
+//                             <td>{info.genomicLocation}</td>
+//                             <td>{info.comment}</td>
+//                         </tr>
+//                     );
+//                 });
+
+//                 return (
+//                     <div>
+//                         <table className="table table-striped">
+//                             <thead>
+//                                 <tr>
+//                                     <th>Gene</th>
+//                                     <th>Genomic Location</th>
+//                                     <th>Comment</th>
+//                                 </tr>
+//                             </thead>
+//                             <tbody>{DisplayData}</tbody>
+//                         </table>
+//                     </div>
+//                 );
+//             }
+//         )
+//     }
+// }
+//export default Revue;
+//export default JsonDataDisplay;