fix(reporter): fix matching diplotype-specific recommendations

src/main/java/org/pharmgkb/pharmcat/reporter/model/pgkb/RecommendationAnnotation.java

@@ -182,4 +182,12 @@ public boolean matchesGenotype(Genotype genotype) {
     }
     return genotype.getLookupKeys().stream().anyMatch(k -> RecommendationUtils.mapContains(k, getLookupKey()));
   }
+
+  public boolean matchesDiplotype(Genotype genotype) {
+    if (getLookupKey() == null) {
+      return false;
+    }
+
+    return RecommendationUtils.mapContains(genotype.getDiplotypeKey(), getLookupKey());
+  }
 }

src/main/java/org/pharmgkb/pharmcat/reporter/model/result/Diplotype.java

@@ -1,16 +1,6 @@
 package org.pharmgkb.pharmcat.reporter.model.result;
 
-import java.util.ArrayList;
-import java.util.Arrays;
-import java.util.Collection;
-import java.util.HashMap;
-import java.util.List;
-import java.util.Map;
-import java.util.Objects;
-import java.util.Optional;
-import java.util.Set;
-import java.util.SortedSet;
-import java.util.TreeSet;
+import java.util.*;
 import java.util.stream.Collectors;
 import com.google.gson.annotations.Expose;
 import com.google.gson.annotations.SerializedName;
@@ -90,6 +80,9 @@ public class Diplotype implements Comparable<Diplotype> {
   @Expose
   @SerializedName("phenotypeDataSource")
   private DataSource m_phenotypeDataSource;
+  @Expose
+  @SerializedName("diplotypeKey")
+  private SortedMap<String,Double> m_diplotypeKey = new TreeMap<>(HaplotypeNameComparator.getComparator());
 
 
   /**
@@ -109,6 +102,10 @@ public Diplotype(String gene, Haplotype h1, @Nullable Haplotype h2, Env env, Dat
     m_allele2 = h2;
     annotateDiplotype(env.getPhenotype(m_gene, source));
     m_label = buildLabel(false);
+    addAlleleToDiplotypeKey(h1.getName());
+    if (h2 != null) {
+      addAlleleToDiplotypeKey(h2.getName());
+    }
   }
 
   public Diplotype(String gene, String hap1, @Nullable String hap2, Env env, DataSource source) {
@@ -118,6 +115,10 @@ public Diplotype(String gene, String hap1, @Nullable String hap2, Env env, DataS
     m_allele2 = hap2 == null ? null : env.makeHaplotype(gene, hap2, source);
     annotateDiplotype(env.getPhenotype(m_gene, source));
     m_label = buildLabel(false);
+    addAlleleToDiplotypeKey(hap1);
+    if (hap2 != null) {
+      addAlleleToDiplotypeKey(hap2);
+    }
   }
 
   /**
@@ -344,6 +345,14 @@ public List<String> getLookupKeys() {
     return m_lookupKeys;
   }
 
+  public Map<String,Double> getDiplotypeKey() {
+    return m_diplotypeKey;
+  }
+
+  private void addAlleleToDiplotypeKey(String allele) {
+    m_diplotypeKey.compute(allele, (k, v) -> v == null ? 1 : v + 1);
+  }
+
 
   /**
    * True if this diplotype does not use allele function to assign phenotype but instead relies on the presence or

src/main/java/org/pharmgkb/pharmcat/reporter/model/result/Genotype.java

@@ -5,7 +5,9 @@
 import java.util.HashMap;
 import java.util.List;
 import java.util.Map;
+import java.util.SortedMap;
 import java.util.SortedSet;
+import java.util.TreeMap;
 import java.util.TreeSet;
 import java.util.stream.Collectors;
 import com.google.gson.annotations.Expose;
@@ -22,6 +24,8 @@ public class Genotype implements Comparable<Genotype> {
 
   private transient List<Map<String, Object>> m_lookupKeys;
 
+  private transient SortedMap<String, Object> m_diplotypeKey = new TreeMap<>();
+
 
   /**
    * Private constructor for GSON.
@@ -52,6 +56,8 @@ private void addDiplotype(Diplotype diplotype) {
     }
     m_diplotypes.add(diplotype);
 
+    m_diplotypeKey.put(diplotype.getGene(), diplotype.getDiplotypeKey());
+
     if (m_lookupKeys == null) {
       m_lookupKeys = diplotype.getLookupKeys().stream()
           .map((k) -> {
@@ -109,6 +115,10 @@ public List<Map<String, Object>> getLookupKeys() {
     return m_lookupKeys;
   }
 
+  public Map<String, Object> getDiplotypeKey() {
+    return m_diplotypeKey;
+  }
+
 
   /**
    * Make a List of possible {@link Genotype} objects from different combinations of reporter diplotypes in the given

src/main/java/org/pharmgkb/pharmcat/reporter/model/result/GuidelineReport.java

@@ -146,11 +146,20 @@ public boolean isFda() {
   private void matchAnnotations(GuidelinePackage guidelinePackage, String drugName) {
     HashMultimap<RecommendationAnnotation, Genotype> matchedGenotypes = HashMultimap.create();
     for (Genotype genotype : m_recommendationGenotypes) {
-      guidelinePackage.getRecommendations().stream()
-          .filter(Objects::nonNull)
-          .filter(rec -> rec.appliesToDrug(drugName))
-          .filter(rec -> rec.matchesGenotype(genotype))
-          .forEach(rec -> matchedGenotypes.put(rec, genotype));
+      boolean matchedDiplotype = false;
+      for (RecommendationAnnotation rec : guidelinePackage.getRecommendations()) {
+        if (rec != null && rec.appliesToDrug(drugName) && rec.matchesDiplotype(genotype)) {
+          matchedGenotypes.put(rec, genotype);
+          matchedDiplotype = true;
+        }
+      }
+      if (!matchedDiplotype) {
+        guidelinePackage.getRecommendations().stream()
+            .filter(Objects::nonNull)
+            .filter(rec -> rec.appliesToDrug(drugName))
+            .filter(rec -> rec.matchesGenotype(genotype))
+            .forEach(rec -> matchedGenotypes.put(rec, genotype));
+      }
     }
     if (drugName.equals("warfarin") && m_source == PrescribingGuidanceSource.CPIC_GUIDELINE) {
       AnnotationReport ann = AnnotationReport.forCpicWarfarin(m_recommendationGenotypes);

src/test/java/org/pharmgkb/pharmcat/PipelineTest.java

@@ -1701,8 +1701,11 @@ void testRecommendationExamples(TestInfo testInfo) throws Exception {
     testWrapper.testMatchedAnnotations("flucloxacillin", PrescribingGuidanceSource.DPWG_GUIDELINE, 1);
     testWrapper.testNoMatchFromSource("fluvoxamine", PrescribingGuidanceSource.CPIC_GUIDELINE);
     testWrapper.testNoMatchFromSource("fluvoxamine", PrescribingGuidanceSource.DPWG_GUIDELINE);
-    testWrapper.testMatchedAnnotations("siponimod", 1);
+
+    // siponimod has DPWG & FDA recs, DPWG uses traditional matching and FDA uses diplotype-specific matching
+    testWrapper.testMatchedAnnotations("siponimod", 2);
     testWrapper.testAnyMatchFromSource("siponimod", PrescribingGuidanceSource.DPWG_GUIDELINE);
+    testWrapper.testAnyMatchFromSource("siponimod", PrescribingGuidanceSource.FDA_LABEL);
 
     testWrapper.testMatchedAnnotations("carbamazepine", PrescribingGuidanceSource.CPIC_GUIDELINE, 3);
     testWrapper.testMatchedAnnotations("carbamazepine", PrescribingGuidanceSource.DPWG_GUIDELINE, 1);
@@ -2381,6 +2384,34 @@ void testOutsideSinglePositionCalls(TestInfo testInfo) throws Exception {
   }
 
 
+  /**
+   * This test ensures diplotype-specific recommendations override more generic phenotype-specific ones.
+   * Specifically, phenytoin has a recommendation for "poor metabolizers" which *2/*2 will match. However, it also has a
+   * recommendation for *2/*2 specifically which should "override" the poor metabolizer recommendation for this specific
+   * diplotype.
+   */
+  @Test
+  void testDiplotypeOverrideRecommendation(TestInfo testInfo) throws Exception {
+    PipelineWrapper testWrapper = new PipelineWrapper(testInfo, false);
+    testWrapper.getVcfBuilder()
+        .reference("CYP2C9")
+        .variation("CYP2C9", "rs1799853", "T", "T");
+    testWrapper.execute();
+
+    testWrapper.testCalledByMatcher("CYP2C9");
+    testWrapper.testPrintCpicCalls( "CYP2C9", "*2/*2");
+    testWrapper.testSourceDiplotypes(DataSource.CPIC, "CYP2C9", List.of("*2/*2"));
+    testWrapper.testSourceDiplotypes(DataSource.DPWG, "CYP2C9", List.of("*2/*2"));
+
+    DrugReport phenytoin = testWrapper.getContext().getDrugReport(PrescribingGuidanceSource.DPWG_GUIDELINE, "phenytoin");
+    assertNotNull(phenytoin);
+    List<AnnotationReport> recs = phenytoin.getGuidelines().stream().flatMap((g) -> g.getAnnotations().stream()).toList();
+    assertEquals(1, recs.size());
+    AnnotationReport matchingRec = recs.get(0);
+    assertEquals("DPWG-PA166299254", recs.get(0).getLocalId());
+  }
+
+
   @Test
   void testDuplicateEntrySecondIsBad(TestInfo testInfo) throws Exception {
     PipelineWrapper testWrapper = new PipelineWrapper(testInfo, false);

src/test/java/org/pharmgkb/pharmcat/reporter/RecommendationUtilsTest.java

@@ -33,5 +33,13 @@ void testMapContains() {
     // changing the value for key that exists in both maps should break containment
     mapA.put("key1", "valueChanged");
     assertFalse(RecommendationUtils.mapContains(mapA, mapB));
+
+    Map<String, Object> mapC = new HashMap<>();
+    Map<String, Object> mapD = new HashMap<>();
+    mapC.put("key1", Map.of("a1", 2));
+    mapC.put("key2", Map.of("a2", 2));
+    mapD.put("key1", Map.of("a1", 2));
+
+    assertTrue(RecommendationUtils.mapContains(mapC, mapD));
   }
 }