fix(namedallelematcher): fix permutation generation with mix of phase…

…d/unphased data
PharmGKB · Aug 27, 2024 · 2146db0 · 2146db0
1 parent fb1ebbd
commit 2146db0
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Showing 3 changed files with 64 additions and 4 deletions.
diff --git a/src/main/java/org/pharmgkb/pharmcat/haplotype/CombinationUtil.java b/src/main/java/org/pharmgkb/pharmcat/haplotype/CombinationUtil.java
@@ -20,14 +20,14 @@ public class CombinationUtil {
    */
   public static Set<String> generatePermutations(List<SampleAllele> alleles) {
     Preconditions.checkNotNull(alleles);
-    Preconditions.checkArgument(alleles.size() > 0, "No alleles to generate permutations for");
+    Preconditions.checkArgument(!alleles.isEmpty(), "No alleles to generate permutations for");
 
     boolean isHaploid = alleles.stream().allMatch(sa -> sa.getAllele2() == null);
     Set<String> rez = generatePermutations(alleles, 0, isHaploid, true, "");
-    if (alleles.get(0).isEffectivelyPhased() && !isHaploid) {
+    if (!isHaploid) {
       rez.addAll(generatePermutations(alleles, 0, false, false, ""));
     }
-    if (rez.size() == 0) {
+    if (rez.isEmpty()) {
       throw new IllegalStateException("No permutations generated from " + alleles.size() + " alleles");
     }
     return rez;

diff --git a/src/test/java/org/pharmgkb/pharmcat/TestVcfBuilder.java b/src/test/java/org/pharmgkb/pharmcat/TestVcfBuilder.java
@@ -10,6 +10,7 @@
 import java.util.HashMap;
 import java.util.List;
 import java.util.Map;
+import java.util.Optional;
 import org.checkerframework.checker.nullness.qual.Nullable;
 import org.junit.jupiter.api.TestInfo;
 import org.pharmgkb.pharmcat.definition.DefinitionReader;
@@ -86,13 +87,29 @@ public TestVcfBuilder variation(String gene, String rsid, String... cpicAlleles)
     return this;
   }
 
+  public TestVcfBuilder variation(String gene, String rsid, boolean isPhased, String... cpicAlleles) {
+    VcfEdit edit = new VcfEdit(rsid, cpicAlleles);
+    edit.isPhased = isPhased;
+    m_edits.computeIfAbsent(gene, g -> new HashMap<>())
+        .put(edit.id, edit);
+    return this;
+  }
+
   public TestVcfBuilder variation(String gene, String chrom, long position, String... cpicAlleles) {
     VcfEdit edit = new VcfEdit(chrom, position, cpicAlleles);
     m_edits.computeIfAbsent(gene, g -> new HashMap<>())
         .put(edit.id, edit);
     return this;
   }
 
+  public TestVcfBuilder variation(String gene, String chrom, long position, boolean isPhased, String... cpicAlleles) {
+    VcfEdit edit = new VcfEdit(chrom, position, cpicAlleles);
+    edit.isPhased = isPhased;
+    m_edits.computeIfAbsent(gene, g -> new HashMap<>())
+        .put(edit.id, edit);
+    return this;
+  }
+
   public TestVcfBuilder variationAsIs(String gene, String rsid, String gt, String ref, String... vcfAltAlleles) {
     VcfEdit edit = new VcfEdit(rsid, null);
     edit.gt = gt;
@@ -318,7 +335,11 @@ private void handleCustomEdit(DefinitionFile definitionFile, PrintWriter writer,
     StringBuilder builder = new StringBuilder();
     for (String cpicAllele : edit.cpicAlleles) {
       if (!builder.isEmpty()) {
-        builder.append(m_isPhased ? "|" : "/");
+        if (edit.isPhased == null) {
+          builder.append(m_isPhased ? "|" : "/");
+        } else {
+          builder.append(edit.isPhased ? "|" : "/");
+        }
       }
       String vcfAllele = vl.getCpicToVcfAlleleMap().get(cpicAllele);
       if (vcfAllele == null) {
@@ -364,6 +385,7 @@ private static class VcfEdit {
     private String[] vcfAltAlleles;
     private String ref;
     private String gt;
+    private Boolean isPhased;
 
     private VcfEdit(String rsid, @Nullable String[] cpicAlleles) {
       this.id = rsid;

diff --git a/src/test/java/org/pharmgkb/pharmcat/haplotype/NamedAlleleMatcherTest.java b/src/test/java/org/pharmgkb/pharmcat/haplotype/NamedAlleleMatcherTest.java
@@ -971,6 +971,44 @@ void testUnknownAltMultisample() throws Exception {
   }
 
 
+  /**
+   * This tests permutation generation works as expected when we get all phased data, all unphased data, and a mix of
+   * phased and unphased data.
+   */
+  @Test
+  void testPermutationGeneration(TestInfo testInfo) throws Exception {
+    Path definitionFile = DataManager.DEFAULT_DEFINITION_DIR.resolve("CYP2C19_translation.json");
+
+    // all phased
+    assertDiplotypePairs(Lists.newArrayList("*2/*17"), testMatchNamedAlleles(definitionFile,
+        new TestVcfBuilder(testInfo, "*2/*17")
+            .phased()
+            .variation("CYP2C19", "rs12248560", "C", "T")
+            .variation("CYP2C19", "rs12769205", "G", "A")
+            .variation("CYP2C19", "rs4244285", "A", "G")
+            .variation("CYP2C19", "rs3758581", "G", "G")
+            .generate()));
+
+    // all unphased
+    assertDiplotypePairs(Lists.newArrayList("*2/*17"), testMatchNamedAlleles(definitionFile,
+        new TestVcfBuilder(testInfo, "*2/*17")
+            .variation("CYP2C19", "rs12248560", "C", "T")
+            .variation("CYP2C19", "rs12769205", "G", "A")
+            .variation("CYP2C19", "rs4244285", "A", "G")
+            .variation("CYP2C19", "rs3758581", "G", "G")
+            .generate()));
+
+    // mix of phased and unphased
+    assertDiplotypePairs(Lists.newArrayList("*2/*17"), testMatchNamedAlleles(definitionFile,
+        new TestVcfBuilder(testInfo, "*2/*17")
+            .variation("CYP2C19", "rs12248560", "C", "T")
+            .variation("CYP2C19", "rs12769205", true, "G", "A")
+            .variation("CYP2C19", "rs4244285", true, "A", "G")
+            .variation("CYP2C19", "rs3758581", "G", "G")
+            .generate()));
+  }
+
+
   @SuppressWarnings("unused")
   private static void printWarnings(Result result) {
     for (String key : result.getVcfWarnings().keySet()) {