package jalview.ext.ensembl;
+import jalview.analysis.AlignmentUtils;
import jalview.datamodel.Alignment;
import jalview.datamodel.AlignmentI;
import jalview.datamodel.DBRefEntry;
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.schemes.ResidueProperties;
import jalview.util.DBRefUtils;
import jalview.util.MapList;
+import jalview.util.MappingUtils;
+import jalview.util.StringUtils;
import java.io.IOException;
import java.net.MalformedURLException;
import java.util.Arrays;
import java.util.Collections;
import java.util.Comparator;
+import java.util.LinkedHashMap;
import java.util.List;
+import java.util.Map.Entry;
/**
* Base class for Ensembl sequence fetchers
*/
public abstract class EnsemblSeqProxy extends EnsemblRestClient
{
+ private static final List<String> CROSS_REFERENCES = Arrays
+ .asList(new String[] { "CCDS", "Uniprot/SWISSPROT" });
+
+ protected static final String CONSEQUENCE_TYPE = "consequence_type";
+
+ protected static final String PARENT = "Parent";
+
+ protected static final String ID = "ID";
+
+ protected static final String NAME = "Name";
+
+ /*
+ * 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 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");
return (forwards ? 1 : -1) * Integer.compare(o1[0], o2[0]);
}
- };
+ }
/**
* Constructor
/**
* Makes the sequence queries to Ensembl's REST service and returns an
- * alignment consisting of the returned sequences
+ * alignment consisting of the returned sequences.
*/
@Override
public AlignmentI getSequenceRecords(String query) throws Exception
// danger: accession separator used as a regex here, a string elsewhere
// in this case it is ok (it is just a space), but (e.g.) '\' would not be
- List<String> allIds = Arrays.asList(query.split(getAccessionSeparator()));
+ List<String> allIds = Arrays.asList(query
+ .split(getAccessionSeparator()));
AlignmentI alignment = null;
inProgress = true;
+ " chunks. Unexpected problem (" + r.getLocalizedMessage()
+ ")";
System.err.println(msg);
- if (alignment != null)
- {
- break; // return what we got
- }
- else
- {
- throw new JalviewException(msg, r);
- }
+ break;
}
}
+ if (alignment == null)
+ {
+ return null;
+ }
+
/*
- * fetch and transfer genomic sequence features
+ * fetch and transfer genomic sequence features,
+ * fetch protein product and add as cross-reference
*/
for (String accId : allIds)
{
addFeaturesAndProduct(accId, alignment);
}
- inProgress = false;
+ for (SequenceI seq : alignment.getSequences())
+ {
+ getCrossReferences(seq);
+ }
+
return alignment;
}
*/
protected void addFeaturesAndProduct(String accId, AlignmentI alignment)
{
+ if (alignment == null)
+ {
+ return;
+ }
+
try
{
/*
* get 'dummy' genomic sequence with exon, cds and variation features
*/
- EnsemblOverlap gffFetcher = new EnsemblOverlap();
+ SequenceI genomicSequence = null;
+ EnsemblFeatures gffFetcher = new EnsemblFeatures();
EnsemblFeatureType[] features = getFeaturesToFetch();
AlignmentI geneFeatures = gffFetcher.getSequenceRecords(accId,
features);
if (geneFeatures.getHeight() > 0)
{
+ genomicSequence = geneFeatures.getSequenceAt(0);
+ }
+ if (genomicSequence != null)
+ {
/*
* transfer features to the query sequence
*/
- SequenceI genomicSequence = geneFeatures.getSequenceAt(0);
SequenceI querySeq = alignment.findName(accId);
- transferFeatures(accId, genomicSequence, querySeq);
+ if (transferFeatures(accId, genomicSequence, querySeq))
+ {
- /*
- * fetch and map protein product, and add it as a cross-reference
- * of the retrieved sequence
- */
- addProteinProduct(querySeq);
+ /*
+ * fetch and map protein product, and add it as a cross-reference
+ * of the retrieved sequence
+ */
+ addProteinProduct(querySeq);
+ }
}
} catch (IOException e)
{
MapList mapList = mapCdsToProtein(querySeq, proteinSeq);
if (mapList != null)
{
- Mapping map = new Mapping(proteinSeq.getDatasetSequence(), mapList);
+ // clunky: ensure Uniprot xref if we have one is on mapped sequence
+ SequenceI ds = proteinSeq.getDatasetSequence();
+ ds.setSourceDBRef(proteinSeq.getSourceDBRef());
+ Mapping map = new Mapping(ds, mapList);
DBRefEntry dbr = new DBRefEntry(getDbSource(), getDbVersion(),
accId, map);
querySeq.getDatasetSequence().addDBRef(dbr);
+
+ /*
+ * compute peptide variants from dna variants and add as
+ * sequence features on the protein sequence ta-da
+ */
+ computeProteinFeatures(querySeq, proteinSeq, mapList);
}
} catch (Exception e)
{
}
/**
+ * Get database xrefs from Ensembl, and attach them to the sequence
+ *
+ * @param seq
+ */
+ protected void getCrossReferences(SequenceI seq)
+ {
+ while (seq.getDatasetSequence() != null)
+ {
+ seq = seq.getDatasetSequence();
+ }
+
+ EnsemblXref xrefFetcher = new EnsemblXref();
+ List<DBRefEntry> xrefs = xrefFetcher.getCrossReferences(seq.getName(),
+ getCrossReferenceDatabases());
+ for (DBRefEntry xref : xrefs)
+ {
+ seq.addDBRef(xref);
+ /*
+ * Save any Uniprot xref to be the reference for SIFTS mapping
+ */
+ if (DBRefSource.UNIPROT.equals(xref.getSource()))
+ {
+ seq.setSourceDBRef(xref);
+ }
+ }
+ }
+
+ /**
+ * Returns a list of database names to be used when fetching cross-references.
+ *
+ * @return
+ */
+ protected List<String> getCrossReferenceDatabases()
+ {
+ return CROSS_REFERENCES;
+ }
+
+ /**
* Returns a mapping from dna to protein by inspecting sequence features of
* type "CDS" on the dna.
*
*/
protected MapList mapCdsToProtein(SequenceI dnaSeq, SequenceI proteinSeq)
{
- SequenceFeature[] sfs = dnaSeq.getSequenceFeatures();
- if (sfs == null)
- {
- return null;
- }
-
List<int[]> ranges = new ArrayList<int[]>(50);
- SequenceOntology so = SequenceOntology.getInstance();
- int mappedDnaLength = 0;
-
+ int mappedDnaLength = getCdsRanges(dnaSeq, ranges);
+
+ int proteinLength = proteinSeq.getLength();
+ int proteinEnd = proteinLength;
+ int proteinStart = 1;
+
/*
- * 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.
+ * incomplete start codon may mean X at start of peptide
+ * we ignore both for mapping purposes
*/
- for (SequenceFeature sf : sfs)
+ if (proteinSeq.getCharAt(0) == 'X')
{
- /*
- * process a CDS feature (or a sub-type of CDS)
- */
- if (so.isA(sf.getType(), SequenceOntology.CDS))
- {
- ranges.add(new int[] { sf.getBegin(), sf.getEnd() });
- mappedDnaLength += Math.abs(sf.getEnd() - sf.getBegin()) + 1;
- }
+ proteinStart = 2;
+ proteinLength--;
}
- int proteinLength = proteinSeq.getLength();
List<int[]> proteinRange = new ArrayList<int[]>();
- proteinRange.add(new int[] { 1, proteinLength });
/*
- * dna length should map to protein (or protein minus stop codon)
+ * dna length should map to protein (or protein plus stop codon)
*/
- if (mappedDnaLength == 3 * proteinLength
- || mappedDnaLength == 3 * (proteinLength + 1))
+ int codesForResidues = mappedDnaLength / 3;
+ if (codesForResidues == (proteinLength + 1))
+ {
+ MappingUtils.unmapStopCodon(ranges, mappedDnaLength);
+ codesForResidues--;
+ }
+ if (codesForResidues == proteinLength)
{
+ proteinRange.add(new int[] { proteinStart, proteinEnd });
return new MapList(ranges, proteinRange, 3, 1);
}
return null;
}
/**
+ * Adds CDS ranges to the ranges list, and returns the total length mapped
+ * from.
+ *
+ * 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.
+ *
+ * @param dnaSeq
+ * @param ranges
+ * @return
+ */
+ protected int getCdsRanges(SequenceI dnaSeq, List<int[]> ranges)
+ {
+ SequenceFeature[] sfs = dnaSeq.getSequenceFeatures();
+ if (sfs == null)
+ {
+ return 0;
+ }
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ int mappedDnaLength = 0;
+ for (SequenceFeature sf : sfs)
+ {
+ /*
+ * process a CDS feature (or a sub-type of CDS)
+ */
+ if (so.isA(sf.getType(), SequenceOntologyI.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())
+ {
+ begin += phase;
+ if (begin > end)
+ {
+ continue; // shouldn't happen?
+ }
+ }
+ ranges.add(new int[] { begin, end });
+ mappedDnaLength += Math.abs(end - begin) + 1;
+ }
+ }
+ return mappedDnaLength;
+ }
+
+ /**
* Fetches sequences for the list of accession ids and adds them to the
* alignment. Returns the extended (or created) alignment.
*
"Only retrieved %d sequences for %d query strings", fr
.getSeqs().size(), ids.size()));
}
+
+ if (fr.getSeqs().size() == 1 && fr.getSeqs().get(0).getLength() == 0)
+ {
+ /*
+ * POST request has returned an empty FASTA file e.g. for invalid id
+ */
+ throw new IOException("No data returned for " + ids);
+ }
+
if (fr.getSeqs().size() > 0)
{
AlignmentI seqal = new Alignment(
@Override
protected URL getUrl(List<String> ids) throws MalformedURLException
{
- // ids are not used - they go in the POST body instead
+ /*
+ * a single id is included in the URL path
+ * multiple ids go in the POST body instead
+ */
StringBuffer urlstring = new StringBuffer(128);
urlstring.append(SEQUENCE_ID_URL);
-
+ if (ids.size() == 1)
+ {
+ urlstring.append("/").append(ids.get(0));
+ }
// @see https://github.com/Ensembl/ensembl-rest/wiki/Output-formats
urlstring.append("?type=").append(getSourceEnsemblType().getType());
urlstring.append(("&Accept=text/x-fasta"));
}
@Override
- public boolean useGetRequest()
+ protected boolean useGetRequest()
{
return false;
}
@Override
- public String getRequestMimeType()
+ protected String getRequestMimeType(boolean multipleIds)
{
- return "application/json";
+ return multipleIds ? "application/json" : "text/x-fasta";
}
@Override
- public String getResponseMimeType()
+ protected String getResponseMimeType()
{
return "text/x-fasta";
}
* backwards (for negative strand). Aborts and returns null if both positive
* and negative strand are found (this should not normally happen).
*
- * @param sfs
+ * @param sourceSequence
* @param accId
+ * @param start
+ * the start position of the sequence we are mapping to
* @return
*/
- protected MapList getGenomicRanges(SequenceFeature[] sfs, String accId)
+ protected MapList getGenomicRangesFromFeatures(SequenceI sourceSequence,
+ String accId, int start)
{
+ SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
+ if (sfs == null)
+ {
+ return null;
+ }
+
/*
- * generously size for initial number of cds regions
+ * generously initial size for number of cds regions
* (worst case titin Q8WZ42 has c. 313 exons)
*/
List<int[]> regions = new ArrayList<int[]>(100);
*/
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;
}
else
{
- regions.add(new int[] { sf.getBegin(), sf.getEnd() });
- }
- mappedLength += Math.abs(sf.getEnd() - sf.getBegin() + 1);
+ regions.add(new int[] { sf.getBegin(), sf.getEnd() });
}
+ mappedLength += Math.abs(sf.getEnd() - sf.getBegin() + 1);
+
+ if (!isSpliceable())
+ {
+ /*
+ * 'gene' sequence is contiguous so we can stop as soon as its
+ * identifying feature has been found
+ */
+ break;
+ }
+ }
}
+ if (regions.isEmpty())
+ {
+ System.out.println("Failed to identify target sequence for " + accId
+ + " from genomic features");
+ return null;
+ }
+
/*
* a final sort is needed since Ensembl returns CDS sorted within source
* (havana / ensembl_havana)
*/
Collections.sort(regions, new RangeSorter(direction == 1));
- List<int[]> to = new ArrayList<int[]>();
- to.add(new int[] { 1, mappedLength });
+ List<int[]> to = Arrays.asList(new int[] { start,
+ start + mappedLength - 1 });
return new MapList(regions, to, 1, 1);
}
/**
- * Returns true if the sequence feature identifies positions of the genomic
- * sequence feature which are within the sequence being retrieved.
+ * Answers true if the sequence being retrieved may occupy discontiguous
+ * regions on the genomic sequence.
+ */
+ protected boolean isSpliceable()
+ {
+ return true;
+ }
+
+ /**
+ * Returns true if the sequence feature marks positions of the genomic
+ * sequence feature which are within the sequence being retrieved. For
+ * example, an 'exon' feature whose parent is the target transcript marks the
+ * cdna positions of the transcript.
*
* @param sf
* @param accId
String accId);
/**
- * Transfers the sequence feature to the target sequence, adjusting its start
- * and end range based on the 'overlap' ranges. Features which do not overlap
- * the target sequence are ignored, as are features with a parent other than
- * the target sequence id.
+ * Transfers the sequence feature to the target sequence, locating its start
+ * and end range based on the mapping. Features which do not overlap the
+ * target sequence are ignored.
*
* @param sf
* @param targetSequence
- * @param overlap
+ * @param mapping
+ * mapping from the sequence feature's coordinates to the target
+ * sequence
*/
protected void transferFeature(SequenceFeature sf,
- SequenceI targetSequence, MapList overlap)
+ SequenceI targetSequence, MapList mapping)
{
- String parent = (String) sf.getValue("Parent");
- if (parent != null && !parent.contains(targetSequence.getName()))
- {
- // this genomic feature belongs to a different transcript
- return;
- }
-
int start = sf.getBegin();
int end = sf.getEnd();
- int[] mappedRange = overlap.locateInTo(start, end);
+ int[] mappedRange = mapping.locateInTo(start, end);
if (mappedRange != null)
{
SequenceFeature copy = new SequenceFeature(sf);
- int offset = targetSequence.getStart() - 1;
- copy.setBegin(offset + Math.min(mappedRange[0], mappedRange[1]));
- copy.setEnd(offset + Math.max(mappedRange[0], mappedRange[1]));
+ copy.setBegin(Math.min(mappedRange[0], mappedRange[1]));
+ copy.setEnd(Math.max(mappedRange[0], mappedRange[1]));
targetSequence.addSequenceFeature(copy);
+
+ /*
+ * for sequence_variant, make an additional feature with consequence
+ */
+ // if (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);
+ // }
+ // }
}
-
}
/**
* @param accessionId
* @param sourceSequence
* @param targetSequence
+ * @return true if any features were transferred, else false
*/
- protected void transferFeatures(String accessionId,
+ protected boolean transferFeatures(String accessionId,
SequenceI sourceSequence, SequenceI targetSequence)
{
if (sourceSequence == null || targetSequence == null)
{
- return;
+ return false;
}
+ // long start = System.currentTimeMillis();
SequenceFeature[] sfs = sourceSequence.getSequenceFeatures();
- MapList overlap = getGenomicRanges(sfs, accessionId);
+ MapList mapping = getGenomicRangesFromFeatures(sourceSequence, accessionId,
+ targetSequence.getStart());
+ if (mapping == null)
+ {
+ return false;
+ }
- final boolean forwardStrand = overlap.isFromForwardStrand();
+ 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;
+ }
+
+ /**
+ * Transfer features to the target sequence. The start/end positions are
+ * converted using the mapping. Features which do not overlap are ignored.
+ * Features whose parent is not the specified identifier are also ignored.
+ *
+ * @param features
+ * @param targetSequence
+ * @param mapping
+ * @param parentId
+ * @return
+ */
+ protected boolean transferFeatures(SequenceFeature[] features,
+ SequenceI targetSequence, MapList mapping, String parentId)
+ {
+ final boolean forwardStrand = mapping.isFromForwardStrand();
/*
* sort features by start position (descending if reverse strand)
* before transferring (in forwards order) to the target sequence
*/
- Arrays.sort(sfs, new Comparator<SequenceFeature>()
+ Arrays.sort(features, new Comparator<SequenceFeature>()
{
@Override
public int compare(SequenceFeature o1, SequenceFeature o2)
}
});
- for (SequenceFeature sf : sfs)
+ boolean transferred = false;
+ for (SequenceFeature sf : features)
{
- if (retainFeature(sf.getType()))
+ if (retainFeature(sf, parentId))
{
- transferFeature(sf, targetSequence, overlap);
+ transferFeature(sf, targetSequence, mapping);
+ transferred = true;
}
}
+ return transferred;
}
/**
- * Answers true if the feature type is one to attach to the retrieved sequence
+ * 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
+ * a CDS sequence).
+ */
+ @SuppressWarnings("unused")
+ protected boolean retainFeature(SequenceFeature sf, String accessionId)
+ {
+ return true; // override as required
+ }
+
+ /**
+ * Answers true if the feature has a Parent which refers to the given
+ * accession id, or if the feature has no parent. Answers false if the
+ * feature's Parent is for a different accession id.
+ *
+ * @param sf
+ * @param identifier
+ * @return
+ */
+ protected boolean featureMayBelong(SequenceFeature sf, String identifier)
+ {
+ String parent = (String) sf.getValue(PARENT);
+ // using contains to allow for prefix "gene:", "transcript:" etc
+ if (parent != null && !parent.contains(identifier))
+ {
+ // this genomic feature belongs to a different transcript
+ return false;
+ }
+ return true;
+ }
+
+ @Override
+ public String getDescription()
+ {
+ return "Ensembl " + getSourceEnsemblType().getType()
+ + " sequence with variant features";
+ }
+
+ /**
+ * Returns a (possibly empty) list of features on the sequence which have the
+ * specified sequence ontology type (or a sub-type of it), and the given
+ * identifier as parent
*
+ * @param sequence
* @param type
+ * @param parentId
+ * @return
+ */
+ protected List<SequenceFeature> findFeatures(SequenceI sequence,
+ String type, String parentId)
+ {
+ List<SequenceFeature> result = new ArrayList<SequenceFeature>();
+
+ SequenceFeature[] sfs = sequence.getSequenceFeatures();
+ if (sfs != null) {
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ for (SequenceFeature sf :sfs) {
+ if (so.isA(sf.getType(), type))
+ {
+ String parent = (String) sf.getValue(PARENT);
+ if (parent.equals(parentId))
+ {
+ result.add(sf);
+ }
+ }
+ }
+ }
+ return result;
+ }
+
+ /**
+ * Maps exon features from dna to protein, and computes variants in peptide
+ * product generated by variants in dna, and adds them as sequence_variant
+ * features on the protein sequence. Returns the number of variant features
+ * added.
+ *
+ * @param dnaSeq
+ * @param peptide
+ * @param dnaToProtein
+ */
+ static int computeProteinFeatures(SequenceI dnaSeq,
+ SequenceI peptide, MapList dnaToProtein)
+ {
+ while (dnaSeq.getDatasetSequence() != null)
+ {
+ dnaSeq = dnaSeq.getDatasetSequence();
+ }
+ while (peptide.getDatasetSequence() != null)
+ {
+ peptide = peptide.getDatasetSequence();
+ }
+
+ AlignmentUtils.transferFeatures(dnaSeq, peptide, dnaToProtein,
+ SequenceOntologyI.EXON);
+
+ LinkedHashMap<Integer, String[][]> variants = buildDnaVariantsMap(
+ dnaSeq, dnaToProtein);
+
+ /*
+ * scan codon variations, compute peptide variants and add to peptide sequence
+ */
+ int count = 0;
+ for (Entry<Integer, String[][]> variant : variants.entrySet())
+ {
+ int peptidePos = variant.getKey();
+ String[][] codonVariants = variant.getValue();
+ String residue = String.valueOf(peptide.getCharAt(peptidePos - 1)); // 0-based
+ List<String> peptideVariants = computePeptideVariants(codonVariants,
+ residue);
+ if (!peptideVariants.isEmpty())
+ {
+ String desc = StringUtils.listToDelimitedString(peptideVariants,
+ ", ");
+ SequenceFeature sf = new SequenceFeature(
+ SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos,
+ peptidePos, 0f, null);
+ peptide.addSequenceFeature(sf);
+ count++;
+ }
+ }
+
+ /*
+ * ugly sort to get sequence features in start position order
+ * - would be better to store in Sequence as a TreeSet instead?
+ */
+ Arrays.sort(peptide.getSequenceFeatures(),
+ new Comparator<SequenceFeature>()
+ {
+ @Override
+ public int compare(SequenceFeature o1, SequenceFeature o2)
+ {
+ int c = Integer.compare(o1.getBegin(), o2.getBegin());
+ return c == 0 ? Integer.compare(o1.getEnd(), o2.getEnd())
+ : c;
+ }
+ });
+ return count;
+ }
+
+ /**
+ * Builds a map whose key is position in the protein sequence, and value is an
+ * array of all variants for the coding codon positions
+ *
+ * @param dnaSeq
+ * @param dnaToProtein
+ * @return
+ */
+ static LinkedHashMap<Integer, String[][]> buildDnaVariantsMap(
+ SequenceI dnaSeq, MapList dnaToProtein)
+ {
+ /*
+ * map from peptide position to all variant features of the codon for it
+ * LinkedHashMap ensures we add the peptide features in sequence order
+ */
+ LinkedHashMap<Integer, String[][]> variants = new LinkedHashMap<Integer, String[][]>();
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+
+ SequenceFeature[] dnaFeatures = dnaSeq.getSequenceFeatures();
+ if (dnaFeatures == null)
+ {
+ return variants;
+ }
+
+ int dnaStart = dnaSeq.getStart();
+ int[] lastCodon = null;
+ int lastPeptidePostion = 0;
+
+ /*
+ * build a map of codon variations for peptides
+ */
+ for (SequenceFeature sf : dnaFeatures)
+ {
+ int dnaCol = sf.getBegin();
+ if (dnaCol != sf.getEnd())
+ {
+ // not handling multi-locus variant features
+ continue;
+ }
+ if (so.isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol);
+ if (mapsTo == null)
+ {
+ // feature doesn't lie within coding region
+ continue;
+ }
+ int peptidePosition = mapsTo[0];
+ String[][] codonVariants = variants.get(peptidePosition);
+ if (codonVariants == null)
+ {
+ codonVariants = new String[3][];
+ variants.put(peptidePosition, codonVariants);
+ }
+
+ /*
+ * extract dna variants to a string array
+ */
+ String alls = (String) sf.getValue("alleles");
+ if (alls == null)
+ {
+ continue;
+ }
+ String[] alleles = alls.split(",");
+
+ /*
+ * get this peptides codon positions e.g. [3, 4, 5] or [4, 7, 10]
+ */
+ int[] codon = peptidePosition == lastPeptidePostion ? lastCodon
+ : MappingUtils.flattenRanges(dnaToProtein.locateInFrom(
+ peptidePosition, peptidePosition));
+ lastPeptidePostion = peptidePosition;
+ lastCodon = codon;
+
+ /*
+ * save nucleotide (and this variant) for each codon position
+ */
+ for (int codonPos = 0; codonPos < 3; codonPos++)
+ {
+ String nucleotide = String.valueOf(dnaSeq
+ .getCharAt(codon[codonPos] - dnaStart));
+ if (codon[codonPos] == dnaCol)
+ {
+ /*
+ * record current dna base and its alleles
+ */
+ String[] dnaVariants = new String[alleles.length + 1];
+ dnaVariants[0] = nucleotide;
+ System.arraycopy(alleles, 0, dnaVariants, 1, alleles.length);
+ codonVariants[codonPos] = dnaVariants;
+ }
+ else if (codonVariants[codonPos] == null)
+ {
+ /*
+ * record current dna base only
+ * (at least until we find any variation and overwrite it)
+ */
+ codonVariants[codonPos] = new String[] { nucleotide };
+ }
+ }
+ }
+ }
+ return variants;
+ }
+
+ /**
+ * Returns a sorted, non-redundant list of all peptide translations generated
+ * by the given dna variants, excluding the current residue value
+ *
+ * @param codonVariants
+ * an array of base values (acgtACGT) for codon positions 1, 2, 3
+ * @param residue
+ * the current residue translation
+ * @return
+ */
+ static List<String> computePeptideVariants(
+ String[][] codonVariants, String residue)
+ {
+ List<String> result = new ArrayList<String>();
+ for (String base1 : codonVariants[0])
+ {
+ for (String base2 : codonVariants[1])
+ {
+ for (String base3 : codonVariants[2])
+ {
+ String codon = base1 + base2 + base3;
+ // TODO: report frameshift/insertion/deletion
+ // and multiple-base variants?!
+ String peptide = codon.contains("-") ? "-" : ResidueProperties
+ .codonTranslate(codon);
+ if (peptide != null && !result.contains(peptide)
+ && !peptide.equalsIgnoreCase(residue))
+ {
+ result.add(peptide);
+ }
+ }
+ }
+ }
+
+ /*
+ * sort alphabetically with STOP at the end
+ */
+ Collections.sort(result, new Comparator<String>()
+ {
+
+ @Override
+ public int compare(String o1, String o2)
+ {
+ if ("STOP".equals(o1))
+ {
+ return 1;
+ }
+ else if ("STOP".equals(o2))
+ {
+ return -1;
+ }
+ else
+ {
+ return o1.compareTo(o2);
+ }
+ }
+ });
+ return result;
+ }
+
+ /**
+ * Answers true if the feature type is either 'NMD_transcript_variant' or
+ * 'transcript' or one of its sub-types in the Sequence Ontology. This is
+ * needed because NMD_transcript_variant behaves like 'transcript' in Ensembl
+ * although strictly speaking it is not (it is a sub-type of
+ * sequence_variant).
+ *
+ * @param featureType
* @return
*/
- protected boolean retainFeature(@SuppressWarnings("unused") String type)
+ public static boolean isTranscript(String featureType)
{
- return true; // default is to keep all
+ return SequenceOntologyI.NMD_TRANSCRIPT_VARIANT.equals(featureType)
+ || SequenceOntologyFactory.getInstance().isA(featureType,
+ SequenceOntologyI.TRANSCRIPT);
}
}