JAL-2738 compute VCF on peptide, extract AF (allele frequency) score

diff --git a/src/jalview/analysis/AlignmentUtils.java b/src/jalview/analysis/AlignmentUtils.java
index 2b9b9f9..41fe77e 100644 (file)
--- a/src/jalview/analysis/AlignmentUtils.java
+++ b/src/jalview/analysis/AlignmentUtils.java
@@ -105,6 +105,15 @@ public class AlignmentUtils
     {
       return variant == null ? null : variant.getFeatureGroup();
     }
+
+    /**
+     * toString for aid in the debugger only
+     */
+    @Override
+    public String toString()
+    {
+      return base + ":" + (variant == null ? "" : variant.getDescription());
+    }
   }
 
   /**
@@ -2542,6 +2551,22 @@ public class AlignmentUtils
         // not handling multi-locus variant features
         continue;
       }
+
+      /*
+       * extract dna variants to a string array
+       */
+      String alls = (String) sf.getValue("alleles");
+      if (alls == null)
+      {
+        continue; // non-SNP VCF variant perhaps - can't process this
+      }
+      String[] alleles = alls.toUpperCase().split(",");
+      int i = 0;
+      for (String allele : alleles)
+      {
+        alleles[i++] = allele.trim(); // lose any space characters "A, G"
+      }
+
       int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol);
       if (mapsTo == null)
       {
@@ -2560,21 +2585,6 @@ public class AlignmentUtils
       }
 
       /*
-       * extract dna variants to a string array
-       */
-      String alls = (String) sf.getValue("alleles");
-      if (alls == null)
-      {
-        continue;
-      }
-      String[] alleles = alls.toUpperCase().split(",");
-      int i = 0;
-      for (String allele : alleles)
-      {
-        alleles[i++] = allele.trim(); // lose any space characters "A, G"
-      }
-
-      /*
        * get this peptide's codon positions e.g. [3, 4, 5] or [4, 7, 10]
        */
       int[] codon = peptidePosition == lastPeptidePostion ? lastCodon

diff --git a/src/jalview/io/vcf/VCFLoader.java b/src/jalview/io/vcf/VCFLoader.java
index d70ffdf..0b13143 100644 (file)
--- a/src/jalview/io/vcf/VCFLoader.java
+++ b/src/jalview/io/vcf/VCFLoader.java
@@ -6,8 +6,11 @@ import htsjdk.variant.variantcontext.VariantContext;
 import htsjdk.variant.vcf.VCFHeader;
 import htsjdk.variant.vcf.VCFHeaderLine;
 
+import jalview.analysis.AlignmentUtils;
 import jalview.datamodel.AlignmentI;
+import jalview.datamodel.DBRefEntry;
 import jalview.datamodel.GeneLoci;
+import jalview.datamodel.Mapping;
 import jalview.datamodel.Sequence;
 import jalview.datamodel.SequenceFeature;
 import jalview.datamodel.SequenceI;
@@ -45,6 +48,7 @@ public class VCFLoader
 
     try
     {
+      long start = System.currentTimeMillis();
       reader = new VCFReader(filePath);
 
       VCFHeader header = reader.getFileHeader();
@@ -58,6 +62,9 @@ public class VCFLoader
       int varCount = 0;
       int seqCount = 0;
 
+      /*
+       * query for VCF overlapping each sequence in turn
+       */
       for (SequenceI seq : al.getSequences())
       {
         int added = loadVCF(seq, reader, isRefGrch37);
@@ -65,11 +72,13 @@ public class VCFLoader
         {
           seqCount++;
           varCount += added;
+          computePeptideVariants(seq);
         }
       }
+      long elapsed = System.currentTimeMillis() - start;
       System.out.println(String.format(
-"Added %d VCF variants to %d sequence(s)", varCount,
-              seqCount));
+              "Added %d VCF variants to %d sequence(s) (%dms)", varCount,
+              seqCount, elapsed));
 
       reader.close();
     } catch (Throwable e)
@@ -80,6 +89,34 @@ public class VCFLoader
   }
 
   /**
+   * (Re-)computes peptide variants from dna variants, for any protein sequence
+   * to which the dna sequence has a mapping. Note that although duplicate
+   * features may get computed, they will not be added, since duplicate sequence
+   * features are ignored in Sequence.addSequenceFeature.
+   * 
+   * @param dnaSeq
+   */
+  protected void computePeptideVariants(SequenceI dnaSeq)
+  {
+    DBRefEntry[] dbrefs = dnaSeq.getDBRefs();
+    if (dbrefs == null)
+    {
+      return;
+    }
+    for (DBRefEntry dbref : dbrefs)
+    {
+      Mapping mapping = dbref.getMap();
+      if (mapping == null || mapping.getTo() == null
+              || mapping.getMap().getFromRatio() != 3)
+      {
+        continue;
+      }
+      AlignmentUtils.computeProteinFeatures(dnaSeq, mapping.getTo(),
+              mapping.getMap());
+    }
+  }
+
+  /**
    * Tries to add overlapping variants read from a VCF file to the given
    * sequence, and returns the number of overlapping variants found. Note that
    * this requires the sequence to hold information as to its chromosomal
@@ -100,16 +137,7 @@ public class VCFLoader
       return 0;
     }
 
-    /*
-     * fudge - ensure chromosomal mapping from range is sequence start/end
-     * (in case end == 0 when the mapping is first created)
-     */
     MapList mapping = seqCoords.getMapping();
-    if (mapping.getFromRanges().get(0)[1] == 0)
-    {
-      mapping.getFromRanges().get(0)[1] = seq.getEnd();
-    }
-
     List<int[]> seqChromosomalContigs = mapping.getToRanges();
     for (int[] range : seqChromosomalContigs)
     {
@@ -202,18 +230,31 @@ public class VCFLoader
     StringBuilder sb = new StringBuilder();
     sb.append(variant.getReference().getBaseString());
 
+    int alleleCount = 0;
     for (Allele allele : variant.getAlleles())
     {
       if (!allele.isReference())
       {
         sb.append(",").append(allele.getBaseString());
+        alleleCount++;
       }
     }
     String alleles = sb.toString(); // e.g. G,A,C
 
     String type = SequenceOntologyI.SEQUENCE_VARIANT;
+    float score = 0f;
+    if (alleleCount == 1)
+    {
+      try
+      {
+        score = (float) variant.getAttributeAsDouble("AF", 0d);
+      } catch (NumberFormatException e)
+      {
+        // leave score as 0
+      }
+    }
     SequenceFeature sf = new SequenceFeature(type, alleles, featureStart,
-            featureEnd, "VCF");
+            featureEnd, score, "VCF");
 
     /*
      * only add 'alleles' property if a SNP, as we can