JAL-2189 source formatting
[jalview.git] / src / jalview / ext / ensembl / EnsemblSeqProxy.java
index a6d838b..9109fb2 100644 (file)
@@ -1,5 +1,8 @@
 package jalview.ext.ensembl;
 
+import jalview.analysis.AlignmentUtils;
+import jalview.analysis.Dna;
+import jalview.bin.Cache;
 import jalview.datamodel.Alignment;
 import jalview.datamodel.AlignmentI;
 import jalview.datamodel.DBRefEntry;
@@ -10,7 +13,9 @@ import jalview.datamodel.SequenceI;
 import jalview.exceptions.JalviewException;
 import jalview.io.FastaFile;
 import jalview.io.FileParse;
-import jalview.io.gff.SequenceOntology;
+import jalview.io.gff.SequenceOntologyFactory;
+import jalview.io.gff.SequenceOntologyI;
+import jalview.util.Comparison;
 import jalview.util.DBRefUtils;
 import jalview.util.MapList;
 
@@ -26,43 +31,43 @@ import java.util.List;
 /**
  * Base class for Ensembl sequence fetchers
  * 
+ * @see http://rest.ensembl.org/documentation/info/sequence_id
  * @author gmcarstairs
  */
 public abstract class EnsemblSeqProxy extends EnsemblRestClient
 {
-  protected static final String CONSEQUENCE_TYPE = "consequence_type";
+  private static final String ALLELES = "alleles";
 
   protected static final String PARENT = "Parent";
 
   protected static final String ID = "ID";
 
-  /*
-   * this needs special handling, as it isA sequence_variant in the
-   * Sequence Ontology, but behaves in Ensembl as if it isA transcript
-   */
-  protected static final String NMD_VARIANT = "NMD_transcript_variant";
-
   protected static final String NAME = "Name";
 
+  protected static final String DESCRIPTION = "description";
+
+  /*
+   * enum for 'type' parameter to the /sequence REST service
+   */
   public enum EnsemblSeqType
   {
     /**
-     * type=genomic for the full dna including introns
+     * type=genomic to fetch full dna including introns
      */
     GENOMIC("genomic"),
 
     /**
-     * type=cdna for transcribed dna including UTRs
+     * type=cdna to fetch coding dna including UTRs
      */
     CDNA("cdna"),
 
     /**
-     * type=cds for coding dna excluding UTRs
+     * type=cds to fetch coding dna excluding UTRs
      */
     CDS("cds"),
 
     /**
-     * type=protein for the peptide product sequence
+     * type=protein to fetch peptide product sequence
      */
     PROTEIN("protein");
 
@@ -105,10 +110,19 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
   }
 
   /**
-   * Constructor
+   * Default constructor (to use rest.ensembl.org)
    */
   public EnsemblSeqProxy()
   {
+    super();
+  }
+
+  /**
+   * Constructor given the target domain to fetch data from
+   */
+  public EnsemblSeqProxy(String d)
+  {
+    super(d);
   }
 
   /**
@@ -118,7 +132,6 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
   @Override
   public AlignmentI getSequenceRecords(String query) throws Exception
   {
-    long now = System.currentTimeMillis();
     // TODO use a String... query vararg instead?
 
     // danger: accession separator used as a regex here, a string elsewhere
@@ -147,17 +160,16 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
                 + " chunks. Unexpected problem (" + r.getLocalizedMessage()
                 + ")";
         System.err.println(msg);
-        if (alignment != null)
-        {
-          break; // return what we got
-        }
-        else
-        {
-          throw new JalviewException(msg, r);
-        }
+        r.printStackTrace();
+        break;
       }
     }
 
+    if (alignment == null)
+    {
+      return null;
+    }
+
     /*
      * fetch and transfer genomic sequence features,
      * fetch protein product and add as cross-reference
@@ -167,9 +179,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
       addFeaturesAndProduct(accId, alignment);
     }
 
-    inProgress = false;
-    System.out.println(getClass().getName() + " took "
-            + (System.currentTimeMillis() - now) + "ms to fetch");
+    for (SequenceI seq : alignment.getSequences())
+    {
+      getCrossReferences(seq);
+    }
+
     return alignment;
   }
 
@@ -195,7 +209,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
        * get 'dummy' genomic sequence with exon, cds and variation features
        */
       SequenceI genomicSequence = null;
-      EnsemblOverlap gffFetcher = new EnsemblOverlap();
+      EnsemblFeatures gffFetcher = new EnsemblFeatures(getDomain());
       EnsemblFeatureType[] features = getFeaturesToFetch();
       AlignmentI geneFeatures = gffFetcher.getSequenceRecords(accId,
               features);
@@ -245,10 +259,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
     String accId = querySeq.getName();
     try
     {
-      AlignmentI protein = new EnsemblProtein().getSequenceRecords(accId);
+      AlignmentI protein = new EnsemblProtein(getDomain())
+              .getSequenceRecords(accId);
       if (protein == null || protein.getHeight() == 0)
       {
-        System.out.println("Failed to retrieve protein for " + accId);
+        System.out.println("No protein product found for " + accId);
         return;
       }
       SequenceI proteinSeq = protein.getSequenceAt(0);
@@ -259,13 +274,63 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
       proteinSeq.createDatasetSequence();
       querySeq.createDatasetSequence();
 
-      MapList mapList = mapCdsToProtein(querySeq, proteinSeq);
+      MapList mapList = AlignmentUtils
+              .mapCdsToProtein(querySeq, proteinSeq);
       if (mapList != null)
       {
-        Mapping map = new Mapping(proteinSeq.getDatasetSequence(), mapList);
-        DBRefEntry dbr = new DBRefEntry(getDbSource(), getDbVersion(),
-                accId, map);
+        // clunky: ensure Uniprot xref if we have one is on mapped sequence
+        SequenceI ds = proteinSeq.getDatasetSequence();
+        // TODO: Verify ensp primary ref is on proteinSeq.getDatasetSequence()
+        Mapping map = new Mapping(ds, mapList);
+        DBRefEntry dbr = new DBRefEntry(getDbSource(),
+                getEnsemblDataVersion(), proteinSeq.getName(), map);
         querySeq.getDatasetSequence().addDBRef(dbr);
+        DBRefEntry[] uprots = DBRefUtils.selectRefs(ds.getDBRefs(),
+                new String[] { DBRefSource.UNIPROT });
+        DBRefEntry[] upxrefs = DBRefUtils.selectRefs(querySeq.getDBRefs(),
+                new String[] { DBRefSource.UNIPROT });
+        if (uprots != null)
+        {
+          for (DBRefEntry up : uprots)
+          {
+            // locate local uniprot ref and map
+            List<DBRefEntry> upx = DBRefUtils.searchRefs(upxrefs,
+                    up.getAccessionId());
+            DBRefEntry upxref;
+            if (upx.size() != 0)
+            {
+              upxref = upx.get(0);
+
+              if (upx.size() > 1)
+              {
+                Cache.log
+                        .warn("Implementation issue - multiple uniprot acc on product sequence.");
+              }
+            }
+            else
+            {
+              upxref = new DBRefEntry(DBRefSource.UNIPROT,
+                      getEnsemblDataVersion(), up.getAccessionId());
+            }
+
+            Mapping newMap = new Mapping(ds, mapList);
+            upxref.setVersion(getEnsemblDataVersion());
+            upxref.setMap(newMap);
+            if (upx.size() == 0)
+            {
+              // add the new uniprot ref
+              querySeq.getDatasetSequence().addDBRef(upxref);
+            }
+
+          }
+        }
+
+        /*
+         * copy exon features to protein, compute peptide variants from dna 
+         * variants and add as features on the protein sequence ta-da
+         */
+        AlignmentUtils
+                .computeProteinFeatures(querySeq, proteinSeq, mapList);
       }
     } catch (Exception e)
     {
@@ -276,85 +341,31 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
   }
 
   /**
-   * Returns a mapping from dna to protein by inspecting sequence features of
-   * type "CDS" on the dna.
+   * Get database xrefs from Ensembl, and attach them to the sequence
    * 
-   * @param dnaSeq
-   * @param proteinSeq
-   * @return
+   * @param seq
    */
-  protected MapList mapCdsToProtein(SequenceI dnaSeq, SequenceI proteinSeq)
+  protected void getCrossReferences(SequenceI seq)
   {
-    SequenceFeature[] sfs = dnaSeq.getSequenceFeatures();
-    if (sfs == null)
+    while (seq.getDatasetSequence() != null)
     {
-      return null;
+      seq = seq.getDatasetSequence();
     }
 
-    List<int[]> ranges = new ArrayList<int[]>(50);
-    SequenceOntology so = SequenceOntology.getInstance();
-
-    int mappedDnaLength = 0;
-    
-    /*
-     * Map CDS columns of dna to peptide. No need to worry about reverse strand
-     * dna here since the retrieved sequence is as transcribed (reverse
-     * complement for reverse strand), i.e in the same sense as the peptide. 
-     */
-    boolean fivePrimeIncomplete = false;
-    for (SequenceFeature sf : sfs)
+    EnsemblXref xrefFetcher = new EnsemblXref(getDomain(), getDbSource(),
+            getEnsemblDataVersion());
+    List<DBRefEntry> xrefs = xrefFetcher.getCrossReferences(seq.getName());
+    for (DBRefEntry xref : xrefs)
     {
-      /*
-       * process a CDS feature (or a sub-type of CDS)
-       */
-      if (so.isA(sf.getType(), SequenceOntology.CDS))
-      {
-        int phase = 0;
-        try {
-          phase = Integer.parseInt(sf.getPhase());
-        } catch (NumberFormatException e)
-        {
-          // ignore
-        }
-        /*
-         * phase > 0 on first codon means 5' incomplete - skip to the start
-         * of the next codon; example ENST00000496384
-         */
-        int begin = sf.getBegin();
-        int end = sf.getEnd();
-        if (ranges.isEmpty() && phase > 0)
-        {
-          fivePrimeIncomplete = true;
-          begin += phase;
-          if (begin > end)
-          {
-            continue; // shouldn't happen?
-          }
-        }
-        ranges.add(new int[] { begin, end });
-        mappedDnaLength += Math.abs(end - begin) + 1;
-      }
+      seq.addDBRef(xref);
     }
-    int proteinLength = proteinSeq.getLength();
-    List<int[]> proteinRange = new ArrayList<int[]>();
-    int proteinStart = 1;
-    if (fivePrimeIncomplete && proteinSeq.getCharAt(0) == 'X')
-    {
-      proteinStart = 2;
-      proteinLength--;
-    }
-    proteinRange.add(new int[] { proteinStart, proteinLength });
 
     /*
-     * dna length should map to protein (or protein plus stop codon)
+     * and add a reference to itself
      */
-    int codesForResidues = mappedDnaLength / 3;
-    if (codesForResidues == proteinLength
-            || codesForResidues == (proteinLength + 1))
-    {
-      return new MapList(ranges, proteinRange, 3, 1);
-    }
-    return null;
+    DBRefEntry self = new DBRefEntry(getDbSource(),
+            getEnsemblDataVersion(), seq.getName());
+    seq.addDBRef(self);
   }
 
   /**
@@ -376,6 +387,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
       throw new JalviewException("ENSEMBL Rest API not available.");
     }
     FileParse fp = getSequenceReader(ids);
+    if (fp == null)
+    {
+      return alignment;
+    }
+
     FastaFile fr = new FastaFile(fp);
     if (fr.hasWarningMessage())
     {
@@ -400,9 +416,8 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
 
     if (fr.getSeqs().size() > 0)
     {
-      AlignmentI seqal = new Alignment(
-              fr.getSeqsAsArray());
-      for (SequenceI sq:seqal.getSequences())
+      AlignmentI seqal = new Alignment(fr.getSeqsAsArray());
+      for (SequenceI sq : seqal.getSequences())
       {
         if (sq.getDescription() == null)
         {
@@ -412,7 +427,9 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
         if (ids.contains(name)
                 || ids.contains(name.replace("ENSP", "ENST")))
         {
-          DBRefUtils.parseToDbRef(sq, DBRefSource.ENSEMBL, "0", name);
+          DBRefEntry dbref = DBRefUtils.parseToDbRef(sq, getDbSource(),
+                  getEnsemblDataVersion(), name);
+          sq.addDBRef(dbref);
         }
       }
       if (alignment == null)
@@ -441,7 +458,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
      * multiple ids go in the POST body instead
      */
     StringBuffer urlstring = new StringBuffer(128);
-    urlstring.append(SEQUENCE_ID_URL);
+    urlstring.append(getDomain() + "/sequence/id");
     if (ids.size() == 1)
     {
       urlstring.append("/").append(ids.get(0));
@@ -515,7 +532,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
    *          the start position of the sequence we are mapping to
    * @return
    */
-  protected MapList getGenomicRanges(SequenceI sourceSequence,
+  protected MapList getGenomicRangesFromFeatures(SequenceI sourceSequence,
           String accId, int start)
   {
     SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
@@ -532,7 +549,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
     int mappedLength = 0;
     int direction = 1; // forward
     boolean directionSet = false;
-  
+
     for (SequenceFeature sf : sfs)
     {
       /*
@@ -541,27 +558,28 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
        */
       if (identifiesSequence(sf, accId))
       {
-          int strand = sf.getStrand();
-  
-          if (directionSet && strand != direction)
-          {
-            // abort - mix of forward and backward
+        int strand = sf.getStrand();
+        strand = strand == 0 ? 1 : strand; // treat unknown as forward
+
+        if (directionSet && strand != direction)
+        {
+          // abort - mix of forward and backward
           System.err.println("Error: forward and backward strand for "
                   + accId);
-            return null;
-          }
-          direction = strand;
-          directionSet = true;
-  
-          /*
-           * add to CDS ranges, semi-sorted forwards/backwards
-           */
-          if (strand < 0)
-          {
-            regions.add(0, new int[] { sf.getEnd(), sf.getBegin() });
-          }
-          else
-          {
+          return null;
+        }
+        direction = strand;
+        directionSet = true;
+
+        /*
+         * add to CDS ranges, semi-sorted forwards/backwards
+         */
+        if (strand < 0)
+        {
+          regions.add(0, new int[] { sf.getEnd(), sf.getBegin() });
+        }
+        else
+        {
           regions.add(new int[] { sf.getBegin(), sf.getEnd() });
         }
         mappedLength += Math.abs(sf.getEnd() - sf.getBegin() + 1);
@@ -576,7 +594,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
         }
       }
     }
-  
+
     if (regions.isEmpty())
     {
       System.out.println("Failed to identify target sequence for " + accId
@@ -589,10 +607,10 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
      * (havana / ensembl_havana)
      */
     Collections.sort(regions, new RangeSorter(direction == 1));
-  
-    List<int[]> to = new ArrayList<int[]>();
-    to.add(new int[] { start, start + mappedLength - 1 });
-  
+
+    List<int[]> to = Arrays.asList(new int[] { start,
+        start + mappedLength - 1 });
+
     return new MapList(regions, to, 1, 1);
   }
 
@@ -628,34 +646,102 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
    * @param mapping
    *          mapping from the sequence feature's coordinates to the target
    *          sequence
+   * @param forwardStrand
    */
   protected void transferFeature(SequenceFeature sf,
-          SequenceI targetSequence, MapList mapping)
+          SequenceI targetSequence, MapList mapping, boolean forwardStrand)
   {
     int start = sf.getBegin();
     int end = sf.getEnd();
     int[] mappedRange = mapping.locateInTo(start, end);
-  
+
     if (mappedRange != null)
     {
       SequenceFeature copy = new SequenceFeature(sf);
       copy.setBegin(Math.min(mappedRange[0], mappedRange[1]));
       copy.setEnd(Math.max(mappedRange[0], mappedRange[1]));
+      if (".".equals(copy.getFeatureGroup()))
+      {
+        copy.setFeatureGroup(getDbSource());
+      }
       targetSequence.addSequenceFeature(copy);
 
       /*
-       * for sequence_variant, make an additional feature with consequence
+       * for sequence_variant on reverse strand, have to convert the allele
+       * values to their complements
        */
-      if (SequenceOntology.getInstance().isSequenceVariant(sf.getType()))
+      if (!forwardStrand
+              && SequenceOntologyFactory.getInstance().isA(sf.getType(),
+                      SequenceOntologyI.SEQUENCE_VARIANT))
       {
-        String consequence = (String) sf.getValue(CONSEQUENCE_TYPE);
-        if (consequence != null)
-        {
-          SequenceFeature sf2 = new SequenceFeature("consequence",
-                  consequence, copy.getBegin(), copy.getEnd(), 0f,
-                  null);
-          targetSequence.addSequenceFeature(sf2);
-        }
+        reverseComplementAlleles(copy);
+      }
+    }
+  }
+
+  /**
+   * Change the 'alleles' value of a feature by converting to complementary
+   * bases, and also update the feature description to match
+   * 
+   * @param sf
+   */
+  static void reverseComplementAlleles(SequenceFeature sf)
+  {
+    final String alleles = (String) sf.getValue(ALLELES);
+    if (alleles == null)
+    {
+      return;
+    }
+    StringBuilder complement = new StringBuilder(alleles.length());
+    for (String allele : alleles.split(","))
+    {
+      reverseComplementAllele(complement, allele);
+    }
+    String comp = complement.toString();
+    sf.setValue(ALLELES, comp);
+    sf.setDescription(comp);
+
+    /*
+     * replace value of "alleles=" in sf.ATTRIBUTES as well
+     * so 'output as GFF' shows reverse complement alleles
+     */
+    String atts = sf.getAttributes();
+    if (atts != null)
+    {
+      atts = atts.replace(ALLELES + "=" + alleles, ALLELES + "=" + comp);
+      sf.setAttributes(atts);
+    }
+  }
+
+  /**
+   * Makes the 'reverse complement' of the given allele and appends it to the
+   * buffer, after a comma separator if not the first
+   * 
+   * @param complement
+   * @param allele
+   */
+  static void reverseComplementAllele(StringBuilder complement,
+          String allele)
+  {
+    if (complement.length() > 0)
+    {
+      complement.append(",");
+    }
+
+    /*
+     * some 'alleles' are actually descriptive terms 
+     * e.g. HGMD_MUTATION, PhenCode_variation
+     * - we don't want to 'reverse complement' these
+     */
+    if (!Comparison.isNucleotideSequence(allele, true))
+    {
+      complement.append(allele);
+    }
+    else
+    {
+      for (int i = allele.length() - 1; i >= 0; i--)
+      {
+        complement.append(Dna.getComplement(allele.charAt(i)));
       }
     }
   }
@@ -676,15 +762,22 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
       return false;
     }
 
+    // long start = System.currentTimeMillis();
     SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
-    MapList mapping = getGenomicRanges(sourceSequence, accessionId,
-            targetSequence.getStart());
+    MapList mapping = getGenomicRangesFromFeatures(sourceSequence,
+            accessionId, targetSequence.getStart());
     if (mapping == null)
     {
       return false;
     }
 
-    return transferFeatures(sfs, targetSequence, mapping, accessionId);
+    boolean result = transferFeatures(sfs, targetSequence, mapping,
+            accessionId);
+    // System.out.println("transferFeatures (" + (sfs.length) + " --> "
+    // + targetSequence.getSequenceFeatures().length + ") to "
+    // + targetSequence.getName()
+    // + " took " + (System.currentTimeMillis() - start) + "ms");
+    return result;
   }
 
   /**
@@ -704,25 +797,18 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
     final boolean forwardStrand = mapping.isFromForwardStrand();
 
     /*
-     * sort features by start position (descending if reverse strand) 
-     * before transferring (in forwards order) to the target sequence
+     * sort features by start position (which corresponds to end
+     * position descending if reverse strand) so as to add them in
+     * 'forwards' order to the target sequence
      */
-    Arrays.sort(features, new Comparator<SequenceFeature>()
-    {
-      @Override
-      public int compare(SequenceFeature o1, SequenceFeature o2)
-      {
-        int c = Integer.compare(o1.getBegin(), o2.getBegin());
-        return forwardStrand ? c : -c;
-      }
-    });
+    sortFeatures(features, forwardStrand);
 
     boolean transferred = false;
     for (SequenceFeature sf : features)
     {
       if (retainFeature(sf, parentId))
       {
-        transferFeature(sf, targetSequence, mapping);
+        transferFeature(sf, targetSequence, mapping, forwardStrand);
         transferred = true;
       }
     }
@@ -730,6 +816,33 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
   }
 
   /**
+   * Sort features by start position ascending (if on forward strand), or end
+   * position descending (if on reverse strand)
+   * 
+   * @param features
+   * @param forwardStrand
+   */
+  protected static void sortFeatures(SequenceFeature[] features,
+          final boolean forwardStrand)
+  {
+    Arrays.sort(features, new Comparator<SequenceFeature>()
+    {
+      @Override
+      public int compare(SequenceFeature o1, SequenceFeature o2)
+      {
+        if (forwardStrand)
+        {
+          return Integer.compare(o1.getBegin(), o2.getBegin());
+        }
+        else
+        {
+          return Integer.compare(o2.getEnd(), o1.getEnd());
+        }
+      }
+    });
+  }
+
+  /**
    * Answers true if the feature type is one we want to keep for the sequence.
    * Some features are only retrieved in order to identify the sequence range,
    * and may then be discarded as redundant information (e.g. "CDS" feature for
@@ -783,11 +896,13 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
           String type, String parentId)
   {
     List<SequenceFeature> result = new ArrayList<SequenceFeature>();
-    
+
     SequenceFeature[] sfs = sequence.getSequenceFeatures();
-    if (sfs != null) {
-      SequenceOntology so = SequenceOntology.getInstance();
-      for (SequenceFeature sf :sfs) {
+    if (sfs != null)
+    {
+      SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+      for (SequenceFeature sf : sfs)
+      {
         if (so.isA(sf.getType(), type))
         {
           String parent = (String) sf.getValue(PARENT);
@@ -813,7 +928,8 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient
    */
   public static boolean isTranscript(String featureType)
   {
-    return NMD_VARIANT.equals(featureType)
-            || SequenceOntology.getInstance().isA(featureType, SequenceOntology.TRANSCRIPT);
+    return SequenceOntologyI.NMD_TRANSCRIPT_VARIANT.equals(featureType)
+            || SequenceOntologyFactory.getInstance().isA(featureType,
+                    SequenceOntologyI.TRANSCRIPT);
   }
 }