add options to connect to database for c. annotation

README.md

@@ -58,3 +58,13 @@ Installation instructions:
 - Do you want to install any cache files (y/n)? -> y, install GRCh37 or GRCh38 cache
 - Do you want to install any FASTA files (y/n)? -> y, install GRCh37 or GRCh38 FASTA
 - Do you want to install any plugins (y/n)? -> n
+
+## Connect an Ensembl database
+
+In order to annotate c. alterations, you must connect to a MySQL database. For an example of connecting to Ensembl's public database, you would use the defaults 
+show in [application.properties](target/classes/application.properties).
+
+However, Ensembl does not recommend connecting to their public database (as it is very slow), so it is recommended to set up a local copy of their database by following
+the [instructions](https://useast.ensembl.org/info/docs/webcode/mirror/install/ensembl-data.html) on the Ensembl website.
+
+**IMPORTANT: Make sure the ensembl-vep docker image, the cache files, and the MySQL database are all using the same version.**

src/main/java/org/genomenexus/vep_wrapper/VepHgvsController.java

@@ -0,0 +1,100 @@
+package org.genomenexus.vep_wrapper;
+
+import java.io.IOException;
+import java.io.OutputStream;
+import java.util.Arrays;
+import java.util.List;
+
+import javax.servlet.http.HttpServletResponse;
+
+import org.springframework.beans.factory.annotation.Autowired;
+import org.springframework.boot.autoconfigure.condition.ConditionalOnProperty;
+import org.springframework.web.bind.annotation.CrossOrigin;
+import org.springframework.web.bind.annotation.PathVariable;
+import org.springframework.web.bind.annotation.RequestBody;
+import org.springframework.web.bind.annotation.RequestMapping;
+import org.springframework.web.bind.annotation.RequestMethod;
+import org.springframework.web.bind.annotation.RequestParam;
+import org.springframework.web.bind.annotation.RestController;
+
+import io.swagger.annotations.Api;
+import io.swagger.annotations.ApiOperation;
+import io.swagger.annotations.ApiParam;
+
+@RestController
+@CrossOrigin(origins="*")
+@RequestMapping(value= "/vep/human/hgvsc")
+@ConditionalOnProperty(
+    value = "database.enabled",
+    havingValue = "true"
+)
+@Api(tags = "vep-hgvs-controller", description = "VEP HGVS Controller")
+public class VepHgvsController {
+
+    @Autowired
+    private VepRunner vepRunner;
+
+    @RequestMapping(value = "/{hgvsc}",
+        method = RequestMethod.GET,
+        produces = "application/json")
+    @ApiOperation(value = "Retrieves VEP results for single c. variant specified in hgvs syntax (https://ensembl.org/info/docs/tools/vep/vep_formats.html)",
+        nickname = "fetchVepHgvscAnnotationByGET")
+    public void getVepHgvscAnnotation(
+            @ApiParam(value="ENST00000618231.3:c.9G>C", required=true)
+            @PathVariable
+            String hgvsc,
+            @ApiParam("Maximum time (in seconds) to let VEP construct a response (0 = no limit)")
+            @RequestParam(defaultValue = "0")
+            Integer responseTimeout,
+            HttpServletResponse response) {
+        OutputStream out = null;
+        try {
+            out = response.getOutputStream();
+            response.setContentType("application/json");
+            vepRunner.run(Arrays.asList(hgvsc), false, responseTimeout, out, true);
+        } catch (IOException | InterruptedException | VepLaunchFailureException e) {
+            e.printStackTrace();
+            // TODO: throw and handle errors with global exception handler
+        } finally {
+            try {
+                response.flushBuffer();
+            } catch (Throwable e) {
+                e.printStackTrace();
+                // TODO: throw and handle errors with global exception handler
+            }
+        }
+    }
+
+    @RequestMapping(value = "/",
+        method = RequestMethod.POST)
+    @ApiOperation(value = "Retrieves VEP results for multiple c. variants specified in hgvs syntax (https://ensembl.org/info/docs/tools/vep/vep_formats.html)",
+        nickname = "fetchVepHgvscAnnotationsByPOST")
+    public void fetchVepHgvscAnnotationsPOST(
+            @ApiParam(value = "List of variants in ENSEMBL hgvsc format. For example:\n" +
+                    "[\"ENST00000618231.3:c.9G>C\", \"ENST00000471631.1:c.28_33delTCGCGG\"]",
+                    required = true)
+            @RequestBody
+            List<String> hgvscStrings,
+            @ApiParam("Maximum time (in seconds) to let VEP construct a response (0 = no limit)")
+            @RequestParam(defaultValue = "0")
+            Integer responseTimeout,
+            HttpServletResponse response) {
+        OutputStream out = null;
+        try {
+            out = response.getOutputStream();
+            response.setContentType("application/json");
+            vepRunner.run(hgvscStrings, true, responseTimeout, out, true);
+        } catch (IOException | InterruptedException | VepLaunchFailureException e) {
+            e.printStackTrace();
+            // TODO: throw and handle errors with global exception handler
+        } finally {
+            try {
+                response.flushBuffer();
+            } catch (Throwable e) {
+                e.printStackTrace();
+                // TODO: throw and handle errors with global exception handler
+            }
+        }
+        return;
+    }
+}

src/main/java/org/genomenexus/vep_wrapper/VepController.java → src/main/java/org/genomenexus/vep_wrapper/VepRegionController.java

@@ -15,14 +15,14 @@
 
 @RestController
 @CrossOrigin(origins="*") // allow all cross-domain requests
-@RequestMapping(value= "/")
-@Api(tags = "vep-controller", description = "VEP Controller")
-public class VepController {
+@RequestMapping(value= "/vep/human/region")
+@Api(tags = "vep-region-controller", description = "VEP Region Controller")
+public class VepRegionController {
 
     @Autowired
     private VepRunner vepRunner;
 
-    @RequestMapping(value = "/vep/human/region/{region}/{allele}",
+    @RequestMapping(value = "/{region}/{allele}",
         method = RequestMethod.GET,
         produces = "application/json")
     @ApiOperation(value = "Retrieves VEP results for single variant specified in region syntax (https://ensembl.org/info/docs/tools/vep/vep_formats.html)",
@@ -44,7 +44,7 @@ public void getVepAnnotation(
         try {
             out = response.getOutputStream();
             response.setContentType("application/json");
-            vepRunner.run(Arrays.asList(region + "/" + allele), false, responseTimeout, out);
+            vepRunner.run(Arrays.asList(region + "/" + allele), false, responseTimeout, out, false);
         } catch (IOException | InterruptedException | VepLaunchFailureException e) {
             e.printStackTrace();
             // TODO: throw and handle errors with global exception handler
@@ -58,7 +58,7 @@ public void getVepAnnotation(
         }
     }
 
-    @RequestMapping(value = "/vep/human/region",
+    @RequestMapping(value = "/",
         method = RequestMethod.POST)
     @ApiOperation(value = "Retrieves VEP annotations for multiple variants specified in region syntax (https://ensembl.org/info/docs/tools/vep/vep_formats.html)",
         nickname = "fetchVepAnnotationByRegionsPOST")
@@ -83,7 +83,7 @@ public void fetchVepAnnotationByRegionsPOST(
         try {
             out = response.getOutputStream();
             response.setContentType("application/json");
-            vepRunner.run(regions, true, responseTimeout, out);
+            vepRunner.run(regions, true, responseTimeout, out, false);
         } catch (IOException | InterruptedException | VepLaunchFailureException e) {
             e.printStackTrace();
             // TODO: throw and handle errors with global exception handler
@@ -97,5 +97,4 @@ public void fetchVepAnnotationByRegionsPOST(
         }
         return;
     }
-
 }

src/main/java/org/genomenexus/vep_wrapper/VepRunner.java

@@ -40,9 +40,33 @@ public class VepRunner {
     private String vepAssembly;
 
     // Path is relative to the VEP_WORK_DIRECTORY_PATH
-    @Value("${vep.fastaFileRelativePath:homo_sapiens/98_GRCh37/Homo_sapiens.GRCh37.75.dna.primary_assembly.fa.gz}")
+    @Value("${vep.fastaFileRelativePath:homo_sapiens/112_GRCh37/Homo_sapiens.GRCh37.dna.primary_assembly.fa.gz}")
     private String vepFastaFileRelativePath;
 
+    @Value("${database.grch37.host}")
+    private String grch37DatabaseHost;
+
+    @Value("${database.grch37.port}")
+    private String grch37DatabasePort;
+
+    @Value("${database.grch37.user}")
+    private String grch37DatabaseUser;
+
+    @Value("${database.grch37.password}")
+    private String grch37DatabasePassword;
+
+    @Value("${database.grch38.host}")
+    private String grch38DatabaseHost;
+
+    @Value("${database.grch38.port}")
+    private String grch38DatabasePort;
+
+    @Value("${database.grch38.user}")
+    private String grch38DatabaseUser;
+
+    @Value("${database.grch38.password}")
+    private String grch38DatabasePassword;
+
     private Path vepFastaFilePath;
     @Autowired
     private void setVepFastaFilePath() {
@@ -64,21 +88,21 @@ private void createTmpDirIfNecessary() throws IOException {
     }
 
     /**
-     * Create a file containing the regions received in the input query.
-     * Write the user supplied regions from the "regions" argument to an output file.
-     * CAUTION : this function does not sort the regions into chromosomal order. The
+     * Create a file containing the variants received in the input query.
+     * Write the user supplied variants from the "variants" argument to an output file.
+     * CAUTION : this function does not sort the variants into chromosomal order. The
      * VEP command line tool is very slow when the input is not sorted. It is expected
      * that users of the VepRunner will always send requests that have been pre-sorted.
      *
-     * @param regions - the regions as passed by the user
+     * @param variants - the variants as passed by the user
      * @param vepInputFile - the file to be written
      * @return sum of two operands
 
     **/
-    private void constructFileForVepProcessing(List<String> regions, Path vepInputFile) throws IOException {
+    private void constructFileForVepProcessing(List<String> variants, Path vepInputFile) throws IOException {
         try (PrintWriter out = new PrintWriter(Files.newBufferedWriter(vepInputFile))) {
-            for (String region : regions) {
-                out.println(region);
+            for (String variant : variants) {
+                out.println(variant);
             }
             out.close();
         } catch (IOException e) {
@@ -111,7 +135,7 @@ public boolean timeIsExpired(Instant timeToKillProcess) {
         return Instant.now().isAfter(timeToKillProcess);
     }
 
-    public void run(List<String> regions, Boolean convertToListJSON, Integer responseTimeout, OutputStream responseOut)
+    public void run(List<String> variants, Boolean convertToListJSON, Integer responseTimeout, OutputStream responseOut, boolean useDatabase)
             throws IOException, InterruptedException, VepLaunchFailureException {
 
         printWithTimestamp("Running vep");
@@ -120,7 +144,43 @@ public void run(List<String> regions, Boolean convertToListJSON, Integer respons
         Path constructedInputFile = createTempFileForVepInput();
 
         // get vep parameters (use -Dvep.params to change)
-        String vepParameters = System.getProperty("vep.params", String.join(" ",
+        String vepParameters;
+        if (useDatabase) {
+            String databaseHost = "";
+            String databasePort = "";
+            String databaseUser = "";
+            String databasePassword = "";
+
+            if (vepAssembly.equals("GRCh38")) {
+                databaseHost = grch38DatabaseHost;
+                databasePort = grch38DatabasePort;
+                databaseUser = grch38DatabaseUser;
+                databasePassword = grch38DatabasePassword;
+            } else {
+                databaseHost = grch37DatabaseHost;
+                databasePort = grch37DatabasePort;
+                databaseUser = grch37DatabaseUser;
+                databasePassword = grch37DatabasePassword;
+            }
+
+            vepParameters = System.getProperty("vep.params", String.join(" ",
+            "--database",
+                "--host " + databaseHost,
+                "--user " + databaseUser,
+                "--password " + databasePassword,
+                "--port " + databasePort,
+                "--everything",
+                "--hgvsg",
+                "--xref_refseq",
+                "--format hgvs",
+                "--fork " + vepForkCount,
+                "--fasta " + vepFastaFilePath,
+                "--json",
+                "-i " + constructedInputFile,
+                "-o STDOUT",
+                "--no_stats"));
+        } else {
+            vepParameters = System.getProperty("vep.params", String.join(" ",
                 "--cache",
                 "--offline",
                 "--everything",
@@ -134,6 +194,7 @@ public void run(List<String> regions, Boolean convertToListJSON, Integer respons
                 "-i " + constructedInputFile,
                 "-o STDOUT",
                 "--no_stats"));
+        }
 
         // build command
         List<String> commandElements = new ArrayList<String>();
@@ -143,7 +204,7 @@ public void run(List<String> regions, Boolean convertToListJSON, Integer respons
         }
 
         printWithTimestamp("writing constructed input file");
-        constructFileForVepProcessing(regions, constructedInputFile);
+        constructFileForVepProcessing(variants, constructedInputFile);
 
         printWithTimestamp("processing requests");
         printWithTimestamp("process command elements: " + commandElements);

src/main/resources/application.yml

@@ -0,0 +1,12 @@
+database:
+  enabled: true
+  grch37:
+    host: host.docker.internal
+    port: 3306
+    user: root
+    password: AlphaMale1987!!
+  grch38:
+    host: host.docker.internal
+    port: 3307
+    user: root
+    password: my-secret-pw