X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fio%2Fvcf%2FVCFLoader.java;h=7bf7791f2b5d98a916313b804098aa3d088e10e0;hb=e185cfd4324bf9e2277e25cfc280cc8a23e75360;hp=de2f18ad7fa812fefb35350307fff2ed6b1ac322;hpb=4073e96c3cb60f28c01cd91ec7f847cafbf01f78;p=jalview.git

diff --git a/src/jalview/io/vcf/VCFLoader.java b/src/jalview/io/vcf/VCFLoader.java
index de2f18a..7bf7791 100644
--- a/src/jalview/io/vcf/VCFLoader.java
+++ b/src/jalview/io/vcf/VCFLoader.java
@@ -51,6 +51,8 @@ import htsjdk.variant.vcf.VCFInfoHeaderLine;
  */
 public class VCFLoader
 {
+  private static final String DEFAULT_SPECIES = "homo_sapiens";
+
   /**
    * A class to model the mapping from sequence to VCF coordinates. Cases include
    * <ul>
@@ -82,7 +84,7 @@ public class VCFLoader
 
   /*
    * Lookup keys, and default values, for Preference entries that describe
-   * patterns for VCF and VEP fields to capture 
+   * patterns for VCF and VEP fields to capture
    */
   private static final String VEP_FIELDS_PREF = "VEP_FIELDS";
 
@@ -93,6 +95,18 @@ public class VCFLoader
   private static final String DEFAULT_VEP_FIELDS = ".*";// "Allele,Consequence,IMPACT,SWISSPROT,SIFT,PolyPhen,CLIN_SIG";
 
   /*
+   * Lookup keys, and default values, for Preference entries that give
+   * mappings from tokens in the 'reference' header to species or assembly
+   */
+  private static final String VCF_ASSEMBLY = "VCF_ASSEMBLY";
+
+  private static final String DEFAULT_VCF_ASSEMBLY = "assembly19=GRCh37,hs37=GRCh37,grch37=GRCh37,grch38=GRCh38";
+
+  private static final String VCF_SPECIES = "VCF_SPECIES"; // default is human
+
+  private static final String DEFAULT_REFERENCE = "grch37"; // fallback default is human GRCh37
+
+  /*
    * keys to fields of VEP CSQ consequence data
    * see https://www.ensembl.org/info/docs/tools/vep/vep_formats.html
    */
@@ -114,12 +128,6 @@ public class VCFLoader
   private static final String PIPE_REGEX = "\\|";
 
   /*
-   * key for Allele Frequency output by VEP
-   * see http://www.ensembl.org/info/docs/tools/vep/vep_formats.html
-   */
-  private static final String ALLELE_FREQUENCY_KEY = "AF";
-
-  /*
    * delimiter that separates multiple consequence data blocks
    */
   private static final String COMMA = ",";
@@ -155,6 +163,16 @@ public class VCFLoader
   private VCFHeader header;
 
   /*
+   * species (as a valid Ensembl term) the VCF is for 
+   */
+  private String vcfSpecies;
+
+  /*
+   * genome assembly version (as a valid Ensembl identifier) the VCF is for 
+   */
+  private String vcfAssembly;
+
+  /*
    * a Dictionary of contigs (if present) referenced in the VCF file
    */
   private SAMSequenceDictionary dictionary;
@@ -246,12 +264,18 @@ public class VCFLoader
    */
   public SequenceI loadVCFContig(String contig)
   {
-    String ref = header.getOtherHeaderLine(VCFHeader.REFERENCE_KEY)
-            .getValue();
+    VCFHeaderLine headerLine = header.getOtherHeaderLine(VCFHeader.REFERENCE_KEY);
+    if (headerLine == null)
+    {
+      Cache.log.error("VCF reference header not found");
+      return null;
+    }
+    String ref = headerLine.getValue();
     if (ref.startsWith("file://"))
     {
       ref = ref.substring(7);
     }
+    setSpeciesAndAssembly(ref);
 
     SequenceI seq = null;
     File dbFile = new File(ref);
@@ -260,12 +284,12 @@ public class VCFLoader
     {
       HtsContigDb db = new HtsContigDb("", dbFile);
       seq = db.getSequenceProxy(contig);
-      loadSequenceVCF(seq, ref);
+      loadSequenceVCF(seq);
       db.close();
     }
     else
     {
-      System.err.println("VCF reference not found: " + ref);
+      Cache.log.error("VCF reference not found: " + ref);
     }
 
     return seq;
@@ -284,7 +308,9 @@ public class VCFLoader
     {
       VCFHeaderLine ref = header
               .getOtherHeaderLine(VCFHeader.REFERENCE_KEY);
-      String vcfAssembly = ref.getValue();
+      String reference = ref == null ? null : ref.getValue();
+
+      setSpeciesAndAssembly(reference);
 
       int varCount = 0;
       int seqCount = 0;
@@ -294,7 +320,7 @@ public class VCFLoader
        */
       for (SequenceI seq : seqs)
       {
-        int added = loadSequenceVCF(seq, vcfAssembly);
+        int added = loadSequenceVCF(seq);
         if (added > 0)
         {
           seqCount++;
@@ -338,6 +364,71 @@ public class VCFLoader
   }
 
   /**
+   * Attempts to determine and save the species and genome assembly version to
+   * which the VCF data applies. This may be done by parsing the {@code reference}
+   * header line, configured in a property file, or (potentially) confirmed
+   * interactively by the user.
+   * <p>
+   * The saved values should be identifiers valid for Ensembl's REST service
+   * {@code map} endpoint, so they can be used (if necessary) to retrieve the
+   * mapping between VCF coordinates and sequence coordinates.
+   * 
+   * @param reference
+   * @see https://rest.ensembl.org/documentation/info/assembly_map
+   * @see https://rest.ensembl.org/info/assembly/human?content-type=text/xml
+   * @see https://rest.ensembl.org/info/species?content-type=text/xml
+   */
+  protected void setSpeciesAndAssembly(String reference)
+  {
+    if (reference == null)
+    {
+      Cache.log.error("No VCF ##reference found, defaulting to "
+              + DEFAULT_REFERENCE + ":" + DEFAULT_SPECIES);
+      reference = DEFAULT_REFERENCE; // default to GRCh37 if not specified
+    }
+    reference = reference.toLowerCase();
+
+    /*
+     * for a non-human species, or other assembly identifier,
+     * specify as a Jalview property file entry e.g.
+     * VCF_ASSEMBLY = hs37=GRCh37,assembly19=GRCh37
+     * VCF_SPECIES = c_elegans=celegans
+     * to map a token in the reference header to a value
+     */
+    String prop = Cache.getDefault(VCF_ASSEMBLY, DEFAULT_VCF_ASSEMBLY);
+    for (String token : prop.split(","))
+    {
+      String[] tokens = token.split("=");
+      if (tokens.length == 2)
+      {
+        if (reference.contains(tokens[0].trim().toLowerCase()))
+        {
+          vcfAssembly = tokens[1].trim();
+          break;
+        }
+      }
+    }
+
+    vcfSpecies = DEFAULT_SPECIES;
+    prop = Cache.getProperty(VCF_SPECIES);
+    if (prop != null)
+    {
+      for (String token : prop.split(","))
+      {
+        String[] tokens = token.split("=");
+        if (tokens.length == 2)
+        {
+          if (reference.contains(tokens[0].trim().toLowerCase()))
+          {
+            vcfSpecies = tokens[1].trim();
+            break;
+          }
+        }
+      }
+    }
+  }
+
+  /**
    * Opens the VCF file and parses header data
    * 
    * @param filePath
@@ -588,12 +679,11 @@ public class VCFLoader
    * and returns the number of variant features added
    * 
    * @param seq
-   * @param vcfAssembly
    * @return
    */
-  protected int loadSequenceVCF(SequenceI seq, String vcfAssembly)
+  protected int loadSequenceVCF(SequenceI seq)
   {
-    VCFMap vcfMap = getVcfMap(seq, vcfAssembly);
+    VCFMap vcfMap = getVcfMap(seq);
     if (vcfMap == null)
     {
       return 0;
@@ -614,10 +704,9 @@ public class VCFLoader
    * Answers a map from sequence coordinates to VCF chromosome ranges
    * 
    * @param seq
-   * @param vcfAssembly
    * @return
    */
-  private VCFMap getVcfMap(SequenceI seq, String vcfAssembly)
+  private VCFMap getVcfMap(SequenceI seq)
   {
     /*
      * simplest case: sequence has id and length matching a VCF contig
@@ -648,34 +737,28 @@ public class VCFLoader
     String species = seqCoords.getSpeciesId();
     String chromosome = seqCoords.getChromosomeId();
     String seqRef = seqCoords.getAssemblyId();
-    MapList map = seqCoords.getMap();
+    MapList map = seqCoords.getMapping();
 
-    if (!vcfSpeciesMatchesSequence(vcfAssembly, species))
+    // note this requires the configured species to match that
+    // returned with the Ensembl sequence; todo: support aliases?
+    if (!vcfSpecies.equalsIgnoreCase(species))
     {
+      Cache.log.warn("No VCF loaded to " + seq.getName()
+              + " as species not matched");
       return null;
     }
 
-    if (vcfAssemblyMatchesSequence(vcfAssembly, seqRef))
+    if (seqRef.equalsIgnoreCase(vcfAssembly))
     {
       return new VCFMap(chromosome, map);
     }
 
-    if (!"GRCh38".equalsIgnoreCase(seqRef) // Ensembl
-            || !vcfAssembly.contains("Homo_sapiens_assembly19")) // gnomAD
-    {
-      return null;
-    }
-
     /*
-     * map chromosomal coordinates from sequence to VCF if the VCF
-     * data has a different reference assembly to the sequence
+     * VCF data has a different reference assembly to the sequence:
+     * query Ensembl to map chromosomal coordinates from sequence to VCF
      */
-    // TODO generalise for cases other than GRCh38 -> GRCh37 !
-    // - or get the user to choose in a dialog
-
     List<int[]> toVcfRanges = new ArrayList<>();
     List<int[]> fromSequenceRanges = new ArrayList<>();
-    String toRef = "GRCh37";
 
     for (int[] range : map.getToRanges())
     {
@@ -687,12 +770,13 @@ public class VCFLoader
       }
 
       int[] newRange = mapReferenceRange(range, chromosome, "human", seqRef,
-              toRef);
+              vcfAssembly);
       if (newRange == null)
       {
         Cache.log.error(
                 String.format("Failed to map %s:%s:%s:%d:%d to %s", species,
-                        chromosome, seqRef, range[0], range[1], toRef));
+                        chromosome, seqRef, range[0], range[1],
+                        vcfAssembly));
         continue;
       }
       else
@@ -733,62 +817,6 @@ public class VCFLoader
   }
 
   /**
-   * Answers true if we determine that the VCF data uses the same reference
-   * assembly as the sequence, else false
-   * 
-   * @param vcfAssembly
-   * @param seqRef
-   * @return
-   */
-  private boolean vcfAssemblyMatchesSequence(String vcfAssembly,
-          String seqRef)
-  {
-    // TODO improve on this stub, which handles gnomAD and
-    // hopes for the best for other cases
-
-    if ("GRCh38".equalsIgnoreCase(seqRef) // Ensembl
-            && vcfAssembly.contains("Homo_sapiens_assembly19")) // gnomAD
-    {
-      return false;
-    }
-    return true;
-  }
-
-  /**
-   * Answers true if the species inferred from the VCF reference identifier
-   * matches that for the sequence
-   * 
-   * @param vcfAssembly
-   * @param speciesId
-   * @return
-   */
-  boolean vcfSpeciesMatchesSequence(String vcfAssembly, String speciesId)
-  {
-    // PROBLEM 1
-    // there are many aliases for species - how to equate one with another?
-    // PROBLEM 2
-    // VCF ##reference header is an unstructured URI - how to extract species?
-    // perhaps check if ref includes any (Ensembl) alias of speciesId??
-    // TODO ask the user to confirm this??
-
-    if (vcfAssembly.contains("Homo_sapiens") // gnomAD exome data example
-            && "HOMO_SAPIENS".equals(speciesId)) // Ensembl species id
-    {
-      return true;
-    }
-
-    if (vcfAssembly.contains("c_elegans") // VEP VCF response example
-            && "CAENORHABDITIS_ELEGANS".equals(speciesId)) // Ensembl
-    {
-      return true;
-    }
-
-    // this is not a sustainable solution...
-
-    return false;
-  }
-
-  /**
    * Queries the VCF reader for any variants that overlap the mapped chromosome
    * ranges of the sequence, and adds as variant features. Returns the number of
    * overlapping variants found.
@@ -835,33 +863,6 @@ public class VCFLoader
   }
 
   /**
-   * A convenience method to get the AF value for the given alternate allele
-   * index
-   * 
-   * @param variant
-   * @param alleleIndex
-   * @return
-   */
-  protected float getAlleleFrequency(VariantContext variant, int alleleIndex)
-  {
-    float score = 0f;
-    String attributeValue = getAttributeValue(variant,
-            ALLELE_FREQUENCY_KEY, alleleIndex);
-    if (attributeValue != null)
-    {
-      try
-      {
-        score = Float.parseFloat(attributeValue);
-      } catch (NumberFormatException e)
-      {
-        // leave as 0
-      }
-    }
-
-    return score;
-  }
-
-  /**
    * A convenience method to get an attribute value for an alternate allele
    * 
    * @param variant
@@ -981,10 +982,8 @@ public class VCFLoader
       type = getOntologyTerm(consequence);
     }
 
-    float score = getAlleleFrequency(variant, altAlleleIndex);
-
     SequenceFeature sf = new SequenceFeature(type, alleles, featureStart,
-            featureEnd, score, FEATURE_GROUP_VCF);
+            featureEnd, FEATURE_GROUP_VCF);
     sf.setSource(sourceId);
 
     sf.setValue(Gff3Helper.ALLELES, alleles);