Merge pull request genome-nexus#746 from leexgh/intergenic-variant

Add intergenicConsequnceSummaries and variant classification in annotationSummary
leexgh · Aug 27, 2024 · fed300f · fed300f
2 parents a9c84a0 + 2ff71d8
commit fed300f
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Showing 4 changed files with 115 additions and 15 deletions.
diff --git a/.../java/org/cbioportal/genome_nexus/component/annotation/VariantClassificationResolver.java b/.../java/org/cbioportal/genome_nexus/component/annotation/VariantClassificationResolver.java
@@ -11,6 +11,7 @@
 import java.util.HashSet;
 import java.util.Map;
 import java.util.Set;
+import java.util.stream.Collectors;
 
 @Component
 public class VariantClassificationResolver
@@ -46,6 +47,21 @@ public String resolve(VariantAnnotation variantAnnotation, TranscriptConsequence
                 this.consequencePrioritizer.pickHighestPriorityConsequence(transcriptConsequence.getConsequenceTerms()),
                     variantType, isInframe);
         }
+        // if variant has no transcript and has intergenicConsequences instead, try to resolve the variant classification from intergenicConsequences
+        else if (variantAnnotation != null && variantAnnotation.getIntergenicConsequences() != null && !variantAnnotation.getIntergenicConsequences().isEmpty()) {
+            // pick the highest priority consequence from the intergenic consequences
+            // get every getConsequenceTerms() from each intergenic consequence and put in a list
+            variantClassification = this.resolveVariantClassification(
+                this.consequencePrioritizer.pickHighestPriorityConsequence(
+                    variantAnnotation.getIntergenicConsequences()
+                    .stream()
+                    .flatMap(consequence -> consequence.getConsequenceTerms()
+                    .stream())
+                    .collect(Collectors.toList())),
+                    variantType,
+                    isInframe
+            );
+        }
         // use the most severe consequence to resolve the variant classification
         else if (variantAnnotation != null)
         {
@@ -186,9 +202,13 @@ private static Map<String, String> initVariantMap()
         variantMap.put("missense_variant",              "Missense_Mutation");
         variantMap.put("protein_altering_variant",      "Missense_Mutation"); // Not always correct, resolveVariantClassification handles the exceptions
         variantMap.put("coding_sequence_variant",       "Missense_Mutation"); // Not always correct, resolveVariantClassification handles the exceptions
+        variantMap.put("coding_transcript_variant",       "Missense_Mutation"); // Not always correct, resolveVariantClassification handles the exceptions
         variantMap.put("conservative_missense_variant", "Missense_Mutation");
         variantMap.put("rare_amino_acid_variant",       "Missense_Mutation");
         variantMap.put("transcript_amplification",      "Intron");
+        variantMap.put("feature_elongation",      "Feature_Elongation");
+        variantMap.put("feature_truncation",      "Feature_Elongation");
+        variantMap.put("sequence_variant",      "Sequence_Variant");
         variantMap.put("splice_region_variant",         "Splice_Region");
         variantMap.put("splice_donor_region_variant",         "Splice_Region");
         variantMap.put("splice_polypyrimidine_tract_variant",         "Splice_Region");
@@ -216,6 +236,7 @@ private static Map<String, String> initVariantMap()
         variantMap.put("regulatory_region_variant",     "IGR");
         variantMap.put("regulatory_region_amplification",     "IGR");
         variantMap.put("regulatory_region",             "IGR");
+        variantMap.put("regulatory_region_ablation",             "IGR");
         variantMap.put("intergenic_variant",            "IGR");
         variantMap.put("intergenic_region",             "IGR");
         variantMap.put("upstream_gene_variant",         "5'Flank");

diff --git a/model/src/main/java/org/cbioportal/genome_nexus/model/IntergenicConsequenceSummary.java b/model/src/main/java/org/cbioportal/genome_nexus/model/IntergenicConsequenceSummary.java
@@ -0,0 +1,53 @@
+package org.cbioportal.genome_nexus.model;
+
+import java.util.List;
+
+public class IntergenicConsequenceSummary {
+    private String impact;
+
+    public String getImpact()
+    {
+        return impact;
+    }
+
+    public void setImpact(String impact)
+    {
+        this.impact = impact;
+    }
+
+    private String variantAllele;
+
+    public String getVariantAllele()
+    {
+        return variantAllele;
+    }
+
+    public void setVariantAllele(String variantAllele)
+    {
+        this.variantAllele = variantAllele;
+    }
+
+    private List<String> consequenceTerms;
+
+    public List<String> getConsequenceTerms()
+    {
+        return consequenceTerms;
+    }
+
+    public void setConsequenceTerms(List<String> consequenceTerms)
+    {
+        this.consequenceTerms = consequenceTerms;
+    }
+
+    private String variantClassification;
+
+    public String getVariantClassification()
+    {
+        return variantClassification;
+    }
+
+    public void setVariantClassification(String variantClassification)
+    {
+        this.variantClassification = variantClassification;
+    }
+}
diff --git a/model/src/main/java/org/cbioportal/genome_nexus/model/VariantAnnotationSummary.java b/model/src/main/java/org/cbioportal/genome_nexus/model/VariantAnnotationSummary.java
@@ -21,8 +21,8 @@ public class VariantAnnotationSummary
     // most impactful canonical annotation, when looking to pick a single
     // annotation
     private TranscriptConsequenceSummary transcriptConsequenceSummary;
-
     private Vues vues;
+    private List<IntergenicConsequenceSummary> intergenicConsequenceSummaries;
 
     private AlphaMissense alphaMissense;
 
@@ -113,4 +113,12 @@ public Vues getVues() {
     public void setVues(Vues vues) {
         this.vues = vues;
     }
+
+    public List<IntergenicConsequenceSummary> getIntergenicConsequenceSummaries() {
+        return intergenicConsequenceSummaries;
+    }
+
+    public void setIntergenicConsequenceSummaries(List<IntergenicConsequenceSummary> intergenicConsequenceSummaries) {
+        this.intergenicConsequenceSummaries = intergenicConsequenceSummaries;
+    }
 }
diff --git a/...ava/org/cbioportal/genome_nexus/service/internal/VariantAnnotationSummaryServiceImpl.java b/...ava/org/cbioportal/genome_nexus/service/internal/VariantAnnotationSummaryServiceImpl.java
@@ -3,6 +3,8 @@
 import org.cbioportal.genome_nexus.component.annotation.*;
 import org.cbioportal.genome_nexus.model.TranscriptConsequenceSummary;
 import org.cbioportal.genome_nexus.model.VariantAnnotationSummary;
+import org.cbioportal.genome_nexus.model.IntergenicConsequenceSummary;
+import org.cbioportal.genome_nexus.model.IntergenicConsequences;
 import org.cbioportal.genome_nexus.model.RevisedProteinEffectJsonRecord;
 import org.cbioportal.genome_nexus.model.TranscriptConsequence;
 import org.cbioportal.genome_nexus.model.VariantAnnotation;
@@ -21,6 +23,7 @@
 
 import java.io.IOException;
 import java.util.ArrayList;
+import java.util.Collections;
 import java.util.HashMap;
 import java.util.List;
 import java.util.Map;
@@ -109,20 +112,35 @@ public VariantAnnotationSummary getAnnotationSummaryForCanonical(VariantAnnotati
         VariantAnnotationSummary annotationSummary = this.getVariantAnnotationSummary(annotation);
         TranscriptConsequence canonicalTranscript = this.canonicalTranscriptResolver.resolve(annotation);
 
-        if (annotationSummary != null && canonicalTranscript != null)
-        {
-            annotationSummary.setTranscriptConsequenceSummary(this.getTranscriptSummary(annotation, canonicalTranscript, vuesMap));
-            annotationSummary.setCanonicalTranscriptId(canonicalTranscript.getTranscriptId());
-
-            // for backwards compatibility set transcriptConsequences
-            List<TranscriptConsequenceSummary> transcriptConsequences = new ArrayList<>(1);
-            transcriptConsequences.add(annotationSummary.getTranscriptConsequenceSummary());
-            annotationSummary.setTranscriptConsequences(transcriptConsequences);
-            // if this variant is VUE, add Vues infomation
-            if (annotationSummary.getTranscriptConsequenceSummary() != null &&
-                annotationSummary.getTranscriptConsequenceSummary().getIsVue() != null &&
-                annotationSummary.getTranscriptConsequenceSummary().getIsVue() == true) {
-                annotationSummary.setVues(this.vuesMap.get(annotationSummary.getTranscriptConsequenceSummary().getTranscriptId()));
+        if (annotationSummary != null) {
+            if (canonicalTranscript == null && annotation.getIntergenicConsequences() != null && !annotation.getIntergenicConsequences().isEmpty()) {
+                // Set intergenicConsequenceSummaries when variant is "intergenic_variant", add variant classification based on consequence terms.
+                // This is useful for genome nexus annotation pipeline, so when doing curation, those mutations will be filtered out by "IGR" rule, instead of being imported as "MUTATED".
+                List<IntergenicConsequenceSummary> intergenicConsequenceSummaries = new ArrayList<>();
+                for (IntergenicConsequences intergenicConsequence : annotation.getIntergenicConsequences()) {
+                    IntergenicConsequenceSummary intergenicConsequenceSummary = new IntergenicConsequenceSummary();
+                    intergenicConsequenceSummary.setVariantClassification(this.variantClassificationResolver.resolve(annotation, canonicalTranscript));
+                    intergenicConsequenceSummary.setImpact(intergenicConsequence.getImpact());
+                    intergenicConsequenceSummary.setVariantAllele(intergenicConsequence.getVariantAllele());
+                    intergenicConsequenceSummary.setConsequenceTerms(intergenicConsequence.getConsequenceTerms());
+                    intergenicConsequenceSummaries.add(intergenicConsequenceSummary);
+                }
+                annotationSummary.setIntergenicConsequenceSummaries(intergenicConsequenceSummaries);
+            }
+            else {
+                annotationSummary.setTranscriptConsequenceSummary(this.getTranscriptSummary(annotation, canonicalTranscript, vuesMap));
+                annotationSummary.setCanonicalTranscriptId(canonicalTranscript.getTranscriptId());
+                // for backwards compatibility set transcriptConsequences
+                List<TranscriptConsequenceSummary> transcriptConsequences = new ArrayList<>(1);
+                transcriptConsequences.add(annotationSummary.getTranscriptConsequenceSummary());
+                annotationSummary.setTranscriptConsequences(transcriptConsequences);
+
+                // if this variant is VUE, add Vues information
+                if (annotationSummary.getTranscriptConsequenceSummary() != null && 
+                    annotationSummary.getTranscriptConsequenceSummary().getIsVue() != null && 
+                    annotationSummary.getTranscriptConsequenceSummary().getIsVue()) {
+                    annotationSummary.setVues(this.vuesMap.get(annotationSummary.getTranscriptConsequenceSummary().getTranscriptId()));
+                }
             }
         }