Merge pull request #665 from awab-ahmed/fix-decomposed-mnv-codon-change

Fix decomposed mnv codon change
opencb · Sep 12, 2023 · c9af263 · c9af263
2 parents 59d7ad3 + 81dff04
commit c9af263
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Showing 9 changed files with 114 additions and 21 deletions.
diff --git a/cellbase-app/pom.xml b/cellbase-app/pom.xml
@@ -6,7 +6,7 @@
     <parent>
         <groupId>org.opencb.cellbase</groupId>
         <artifactId>cellbase</artifactId>
-        <version>4.12.5</version>
+        <version>4.12.6</version>
         <relativePath>../pom.xml</relativePath>
     </parent>
 

diff --git a/cellbase-client/pom.xml b/cellbase-client/pom.xml
@@ -6,7 +6,7 @@
     <parent>
         <groupId>org.opencb.cellbase</groupId>
         <artifactId>cellbase</artifactId>
-        <version>4.12.5</version>
+        <version>4.12.6</version>
         <relativePath>../pom.xml</relativePath>
     </parent>
 

diff --git a/cellbase-core/pom.xml b/cellbase-core/pom.xml
@@ -6,7 +6,7 @@
     <parent>
         <groupId>org.opencb.cellbase</groupId>
         <artifactId>cellbase</artifactId>
-        <version>4.12.5</version>
+        <version>4.12.6</version>
         <relativePath>../pom.xml</relativePath>
     </parent>
 

diff --git a/...rc/main/java/org/opencb/cellbase/core/variant/annotation/VariantAnnotationCalculator.java b/...rc/main/java/org/opencb/cellbase/core/variant/annotation/VariantAnnotationCalculator.java
@@ -652,9 +652,6 @@ private void adjustPhasedConsequenceTypes(Object[] variantArray) {
                         = findCodingOverlappingConsequenceType(consequenceType1, variant1.getAnnotation().getConsequenceTypes());
                 // The two first variants affect the same codon
                 if (consequenceType2 != null) {
-                    // WARNING: assumes variants are sorted according to their coordinates
-                    int cdnaPosition = consequenceType1.getCdnaPosition();
-                    int cdsPosition = consequenceType1.getCdsPosition();
                     String codon = null;
                     String alternateAA = null;
                     List<SequenceOntologyTerm> soTerms = null;
@@ -673,12 +670,12 @@ private void adjustPhasedConsequenceTypes(Object[] variantArray) {
                         String alternateCodon = null;
 
                         // negative strand
-                        if ("-".equals(variant0.getStrand())) {
-                            alternateCodon = "" + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant2.getAlternate())
-                                            + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant1.getAlternate())
-                                            + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant0.getAlternate());
+                        if ("-".equals(consequenceType1.getStrand())) {
+                            alternateCodon = "" + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant2.getAlternate().toUpperCase().toCharArray()[0])
+                                            + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant1.getAlternate().toUpperCase().toCharArray()[0])
+                                            + VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant0.getAlternate().toUpperCase().toCharArray()[0]);
                         } else {
-                            alternateCodon = variant0.getAlternate() + variant1.getAlternate() + variant2.getAlternate();
+                            alternateCodon = variant0.getAlternate().toUpperCase() + variant1.getAlternate().toUpperCase() + variant2.getAlternate().toUpperCase();
                         }
 
 
@@ -689,8 +686,6 @@ private void adjustPhasedConsequenceTypes(Object[] variantArray) {
                                 variant1.getChromosome().equals("MT"));
 
                         // Update consequenceType3
-                        consequenceType3.setCdnaPosition(cdnaPosition);
-                        consequenceType3.setCdsPosition(cdsPosition);
                         consequenceType3.setCodon(codon);
                         consequenceType3.getProteinVariantAnnotation().setAlternate(alternateAA);
                         newProteinVariantAnnotation = getProteinAnnotation(consequenceType3);
@@ -716,7 +711,7 @@ private void adjustPhasedConsequenceTypes(Object[] variantArray) {
                         char[] alternateCodonArray = referenceCodonArray.clone();
 
                         // negative strand
-                        if ("-".equals(variant0.getStrand())) {
+                        if ("-".equals(consequenceType1.getStrand())) {
                             alternateCodonArray[codonIdx1] =
                                     VariantAnnotationUtils.COMPLEMENTARY_NT.get(variant0.getAlternate().toUpperCase().toCharArray()[0]);
                             alternateCodonArray[codonIdx2] =
@@ -739,8 +734,6 @@ private void adjustPhasedConsequenceTypes(Object[] variantArray) {
                     consequenceType1.setProteinVariantAnnotation(newProteinVariantAnnotation == null
                             ? getProteinAnnotation(consequenceType1) : newProteinVariantAnnotation);
                     consequenceType1.setSequenceOntologyTerms(soTerms);
-                    consequenceType2.setCdnaPosition(cdnaPosition);
-                    consequenceType2.setCdsPosition(cdsPosition);
                     consequenceType2.setCodon(codon);
                     consequenceType2.getProteinVariantAnnotation().setAlternate(alternateAA);
                     consequenceType2.setProteinVariantAnnotation(consequenceType1.getProteinVariantAnnotation());

diff --git a/cellbase-lib/pom.xml b/cellbase-lib/pom.xml
@@ -6,7 +6,7 @@
     <parent>
         <groupId>org.opencb.cellbase</groupId>
         <artifactId>cellbase</artifactId>
-        <version>4.12.5</version>
+        <version>4.12.6</version>
         <relativePath>../pom.xml</relativePath>
     </parent>
 

diff --git a/cellbase-lib/src/test/java/org/opencb/cellbase/lib/impl/VariantAnnotationCalculatorTest.java b/cellbase-lib/src/test/java/org/opencb/cellbase/lib/impl/VariantAnnotationCalculatorTest.java
@@ -799,6 +799,106 @@ public void testQueryResultGroupingDecomposedMNVs() throws Exception {
 
 
 
+    }
+
+
+    @Test
+    public void testDecomposedMNVReturnsCorrectCodonChange() throws Exception {
+        QueryOptions queryOptions = (new QueryOptions("normalize", true));
+        queryOptions.put("skipDecompose", true);
+        queryOptions.put("include", "consequenceType,hgvs");
+        Variant variant = new Variant("18", 30517979, "CC", "AA");
+        String transcriptID = "ENST00000581852";
+        // Negative strand with no decompose
+        QueryResult<VariantAnnotation> queryResult = variantAnnotationCalculator
+                .getAnnotationByVariant(variant, queryOptions);
+        List<ConsequenceType> consequenceTypeList  = queryResult.getResult().get(0).getConsequenceTypes();
+        assertFalse(consequenceTypeList.isEmpty());
+        ConsequenceType consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("-", consequenceType.getStrand());
+        assertEquals("GGT/TTT", consequenceType.getCodon());
+        assertEquals("GLY", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(262, consequenceType.getCdnaPosition().intValue());
+        assertEquals(214, consequenceType.getCdsPosition().intValue());
+        // For negative strand with decompose, amino acid change should be similar to the non-decomposed one
+        queryOptions.put("skipDecompose", false);
+        queryResult = variantAnnotationCalculator
+                .getAnnotationByVariant(variant, queryOptions);
+        // First variant
+        consequenceTypeList  = queryResult.getResult().get(0).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("-", consequenceType.getStrand());
+        assertEquals("GGt/TTt", consequenceType.getCodon());
+        assertEquals("GLY", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(30517979, queryResult.getResult().get(0).getStart().intValue());
+        assertEquals(263, consequenceType.getCdnaPosition().intValue());
+        assertEquals(215, consequenceType.getCdsPosition().intValue());
+        // Second variant
+        consequenceTypeList  = queryResult.getResult().get(1).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("-", consequenceType.getStrand());
+        assertEquals("GGt/TTt", consequenceType.getCodon());
+        assertEquals("GLY", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(30517980, queryResult.getResult().get(1).getStart().intValue());
+        assertEquals(262, consequenceType.getCdnaPosition().intValue());
+        assertEquals(214, consequenceType.getCdsPosition().intValue());
+
+        // Test for negative strand decomposed mnv made of 3 changes in the same codon
+        variant = new Variant("18", 30517978, "ACC", "GGG");
+        queryResult = variantAnnotationCalculator
+                .getAnnotationByVariant(variant, queryOptions);
+        consequenceTypeList  = queryResult.getResult().get(0).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("-", consequenceType.getStrand());
+        assertEquals("GGT/CCC", consequenceType.getCodon());
+        assertEquals("GLY", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PRO", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(30517978, queryResult.getResult().get(0).getStart().intValue());
+        assertEquals(264, consequenceType.getCdnaPosition().intValue());
+        assertEquals(216, consequenceType.getCdsPosition().intValue());
+
+        // Positive strand, no decompose
+        variant = new Variant("19", 33167329, "AC", "TT");
+        transcriptID = "ENST00000334176";
+        queryOptions.put("skipDecompose", true);
+        queryResult = variantAnnotationCalculator
+                .getAnnotationByVariant(variant, queryOptions);
+        consequenceTypeList  = queryResult.getResult().get(0).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("+", consequenceType.getStrand());
+        assertEquals("ACC/TTC", consequenceType.getCodon());
+        assertEquals("THR", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(33167329, queryResult.getResult().get(0).getStart().intValue());
+        assertEquals(1017, consequenceType.getCdnaPosition().intValue());
+        assertEquals(160, consequenceType.getCdsPosition().intValue());
+        // Positive strand with decompose
+        queryOptions.put("skipDecompose", false);
+        queryResult = variantAnnotationCalculator
+                .getAnnotationByVariant(variant, queryOptions);
+        // First variant
+        consequenceTypeList  = queryResult.getResult().get(0).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("+", consequenceType.getStrand());
+        assertEquals("ACc/TTc", consequenceType.getCodon());
+        assertEquals("THR", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(33167329, queryResult.getResult().get(0).getStart().intValue());
+        assertEquals(1017, consequenceType.getCdnaPosition().intValue());
+        assertEquals(160, consequenceType.getCdsPosition().intValue());
+        // Second variant
+        consequenceTypeList  = queryResult.getResult().get(1).getConsequenceTypes();
+        consequenceType = getConsequenceType(consequenceTypeList,transcriptID);
+        assertEquals("+", consequenceType.getStrand());
+        assertEquals("ACc/TTc", consequenceType.getCodon());
+        assertEquals("THR", consequenceType.getProteinVariantAnnotation().getReference());
+        assertEquals("PHE", consequenceType.getProteinVariantAnnotation().getAlternate());
+        assertEquals(33167330, queryResult.getResult().get(1).getStart().intValue());
+        assertEquals(1018, consequenceType.getCdnaPosition().intValue());
+        assertEquals(161, consequenceType.getCdsPosition().intValue());
     }
 
     @Test

diff --git a/cellbase-server/pom.xml b/cellbase-server/pom.xml
@@ -6,7 +6,7 @@
     <parent>
         <groupId>org.opencb.cellbase</groupId>
         <artifactId>cellbase</artifactId>
-        <version>4.12.5</version>
+        <version>4.12.6</version>
         <relativePath>../pom.xml</relativePath>
     </parent>
 

diff --git a/cellbase-test/pom.xml b/cellbase-test/pom.xml
@@ -22,7 +22,7 @@
 
     <groupId>org.opencb.cellbase</groupId>
     <artifactId>cellbase-test</artifactId>
-    <version>4.12.5</version>
+    <version>4.12.6</version>
     <packaging>pom</packaging>
 
     <dependencies>

diff --git a/pom.xml b/pom.xml
@@ -6,7 +6,7 @@
 
     <groupId>org.opencb.cellbase</groupId>
     <artifactId>cellbase</artifactId>
-    <version>4.12.5</version>
+    <version>4.12.6</version>
     <packaging>pom</packaging>
 
     <name>CellBase project</name>
@@ -22,7 +22,7 @@
     </modules>
 
     <properties>
-        <cellbase.version>4.12.5</cellbase.version>
+        <cellbase.version>4.12.6</cellbase.version>
         <compileSource>1.8</compileSource>
         <java-common-libs.version>3.7.5</java-common-libs.version>
         <biodata.version>1.5.6</biodata.version>