--- /dev/null
+package jalview.ext.ensembl;
+
+import jalview.api.FeatureColourI;
+import jalview.api.FeatureSettingsModelI;
+import jalview.datamodel.AlignmentI;
+import jalview.datamodel.Sequence;
+import jalview.datamodel.SequenceFeature;
+import jalview.datamodel.SequenceI;
+import jalview.io.gff.SequenceOntologyFactory;
+import jalview.io.gff.SequenceOntologyI;
+import jalview.schemes.FeatureColourAdapter;
+import jalview.schemes.FeatureSettingsAdapter;
+import jalview.util.MapList;
+import jalview.util.StringUtils;
+
+import java.awt.Color;
+import java.io.UnsupportedEncodingException;
+import java.net.URLDecoder;
+import java.util.ArrayList;
+import java.util.Arrays;
+import java.util.List;
+
+import com.stevesoft.pat.Regex;
+
+/**
+ * A class that fetches genomic sequence and all transcripts for an Ensembl gene
+ *
+ * @author gmcarstairs
+ */
+public class EnsemblGene extends EnsemblSeqProxy
+{
+ private static final List<String> CROSS_REFERENCES = Arrays
+ .asList(new String[] { "CCDS" });
+
+ private static final String GENE_PREFIX = "gene:";
+
+ /*
+ * accepts anything as we will attempt lookup of gene or
+ * transcript id or gene name
+ */
+ private static final Regex ACCESSION_REGEX = new Regex(".*");
+
+ private static final EnsemblFeatureType[] FEATURES_TO_FETCH = {
+ EnsemblFeatureType.gene, EnsemblFeatureType.transcript,
+ EnsemblFeatureType.exon, EnsemblFeatureType.cds,
+ EnsemblFeatureType.variation };
+
+ /**
+ * Default constructor (to use rest.ensembl.org)
+ */
+ public EnsemblGene()
+ {
+ super();
+ }
+
+ /**
+ * Constructor given the target domain to fetch data from
+ *
+ * @param d
+ */
+ public EnsemblGene(String d)
+ {
+ super(d);
+ }
+
+ @Override
+ public String getDbName()
+ {
+ return "ENSEMBL";
+ }
+
+ @Override
+ protected EnsemblFeatureType[] getFeaturesToFetch()
+ {
+ return FEATURES_TO_FETCH;
+ }
+
+ @Override
+ protected EnsemblSeqType getSourceEnsemblType()
+ {
+ return EnsemblSeqType.GENOMIC;
+ }
+
+ /**
+ * Returns an alignment containing the gene(s) for the given gene or
+ * transcript identifier, or external identifier (e.g. Uniprot id). If given a
+ * gene name or external identifier, returns any related gene sequences found
+ * for model organisms. If only a single gene is queried for, then its
+ * transcripts are also retrieved and added to the alignment. <br>
+ * Method:
+ * <ul>
+ * <li>resolves a transcript identifier by looking up its parent gene id</li>
+ * <li>resolves an external identifier by looking up xref-ed gene ids</li>
+ * <li>fetches the gene sequence</li>
+ * <li>fetches features on the sequence</li>
+ * <li>identifies "transcript" features whose Parent is the requested gene</li>
+ * <li>fetches the transcript sequence for each transcript</li>
+ * <li>makes a mapping from the gene to each transcript</li>
+ * <li>copies features from gene to transcript sequences</li>
+ * <li>fetches the protein sequence for each transcript, maps and saves it as
+ * a cross-reference</li>
+ * <li>aligns each transcript against the gene sequence based on the position
+ * mappings</li>
+ * </ul>
+ *
+ * @param query
+ * one or more identifiers separated by a space
+ * @return an alignment containing one or more genes, and possibly
+ * transcripts, or null
+ */
+ @Override
+ public AlignmentI getSequenceRecords(String query) throws Exception
+ {
+ // todo: tidy up handling of one or multiple accession ids
+ String[] queries = query.split(getAccessionSeparator());
+
+ /*
+ * if given a transcript id, look up its gene parent
+ */
+ if (isTranscriptIdentifier(query))
+ {
+ // we are assuming all transcripts have the same gene parent here
+ query = new EnsemblLookup(getDomain()).getParent(queries[0]);
+ if (query == null)
+ {
+ return null;
+ }
+ }
+
+ /*
+ * if given a gene or other external name, lookup and fetch
+ * the corresponding gene for all model organisms
+ */
+ if (!isGeneIdentifier(query))
+ {
+ List<String> geneIds = new EnsemblSymbol(getDomain()).getIds(query);
+ if (geneIds.isEmpty())
+ {
+ return null;
+ }
+ String theIds = StringUtils.listToDelimitedString(geneIds,
+ getAccessionSeparator());
+ return getSequenceRecords(theIds);
+ }
+
+ /*
+ * fetch the gene sequence(s) with features and xrefs
+ */
+ AlignmentI al = super.getSequenceRecords(query);
+
+ /*
+ * if we retrieved a single gene, get its transcripts as well
+ */
+ if (al.getHeight() == 1)
+ {
+ getTranscripts(al, query);
+ }
+
+ return al;
+ }
+
+ /**
+ * Attempts to get Ensembl stable identifiers for model organisms for a gene
+ * name by calling the xrefs symbol REST service to resolve the gene name.
+ *
+ * @param query
+ * @return
+ */
+ protected String getGeneIdentifiersForName(String query)
+ {
+ List<String> ids = new EnsemblSymbol(getDomain()).getIds(query);
+ if (ids != null)
+ {
+ for (String id : ids)
+ {
+ if (isGeneIdentifier(id))
+ {
+ return id;
+ }
+ }
+ }
+ return null;
+ }
+
+ /**
+ * Constructs all transcripts for the gene, as identified by "transcript"
+ * features whose Parent is the requested gene. The coding transcript
+ * sequences (i.e. with introns omitted) are added to the alignment.
+ *
+ * @param al
+ * @param accId
+ * @throws Exception
+ */
+ protected void getTranscripts(AlignmentI al, String accId)
+ throws Exception
+ {
+ SequenceI gene = al.getSequenceAt(0);
+ List<SequenceFeature> transcriptFeatures = getTranscriptFeatures(accId,
+ gene);
+
+ for (SequenceFeature transcriptFeature : transcriptFeatures)
+ {
+ makeTranscript(transcriptFeature, al, gene);
+ }
+
+ clearGeneFeatures(gene);
+ }
+
+ /**
+ * Remove unwanted features (transcript, exon, CDS) from the gene sequence
+ * after we have used them to derive transcripts and transfer features
+ *
+ * @param gene
+ */
+ protected void clearGeneFeatures(SequenceI gene)
+ {
+ SequenceFeature[] sfs = gene.getSequenceFeatures();
+ if (sfs != null)
+ {
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ List<SequenceFeature> filtered = new ArrayList<SequenceFeature>();
+ for (SequenceFeature sf : sfs)
+ {
+ String type = sf.getType();
+ if (!isTranscript(type) && !so.isA(type, SequenceOntologyI.EXON)
+ && !so.isA(type, SequenceOntologyI.CDS))
+ {
+ filtered.add(sf);
+ }
+ }
+ gene.setSequenceFeatures(filtered
+ .toArray(new SequenceFeature[filtered
+ .size()]));
+ }
+ }
+
+ /**
+ * Constructs a spliced transcript sequence by finding 'exon' features for the
+ * given id (or failing that 'CDS'). Copies features on to the new sequence.
+ * 'Aligns' the new sequence against the gene sequence by padding with gaps,
+ * and adds it to the alignment.
+ *
+ * @param transcriptFeature
+ * @param al
+ * the alignment to which to add the new sequence
+ * @param gene
+ * the parent gene sequence, with features
+ * @return
+ */
+ SequenceI makeTranscript(SequenceFeature transcriptFeature,
+ AlignmentI al, SequenceI gene)
+ {
+ String accId = getTranscriptId(transcriptFeature);
+ if (accId == null)
+ {
+ return null;
+ }
+
+ /*
+ * NB we are mapping from gene sequence (not genome), so do not
+ * need to check for reverse strand (gene and transcript sequences
+ * are in forward sense)
+ */
+
+ /*
+ * make a gene-length sequence filled with gaps
+ * we will fill in the bases for transcript regions
+ */
+ char[] seqChars = new char[gene.getLength()];
+ Arrays.fill(seqChars, al.getGapCharacter());
+
+ /*
+ * look for exon features of the transcript, failing that for CDS
+ * (for example ENSG00000124610 has 1 CDS but no exon features)
+ */
+ String parentId = "transcript:" + accId;
+ List<SequenceFeature> splices = findFeatures(gene,
+ SequenceOntologyI.EXON, parentId);
+ if (splices.isEmpty())
+ {
+ splices = findFeatures(gene, SequenceOntologyI.CDS, parentId);
+ }
+
+ int transcriptLength = 0;
+ final char[] geneChars = gene.getSequence();
+ int offset = gene.getStart(); // to convert to 0-based positions
+ List<int[]> mappedFrom = new ArrayList<int[]>();
+
+ for (SequenceFeature sf : splices)
+ {
+ int start = sf.getBegin() - offset;
+ int end = sf.getEnd() - offset;
+ int spliceLength = end - start + 1;
+ System.arraycopy(geneChars, start, seqChars, start, spliceLength);
+ transcriptLength += spliceLength;
+ mappedFrom.add(new int[] { sf.getBegin(), sf.getEnd() });
+ }
+
+ Sequence transcript = new Sequence(accId, seqChars, 1, transcriptLength);
+
+ /*
+ * Ensembl has gene name as transcript Name
+ * EnsemblGenomes doesn't, but has a url-encoded description field
+ */
+ String description = (String) transcriptFeature.getValue(NAME);
+ if (description == null)
+ {
+ description = (String) transcriptFeature.getValue(DESCRIPTION);
+ }
+ if (description != null)
+ {
+ try
+ {
+ transcript.setDescription(URLDecoder.decode(description, "UTF-8"));
+ } catch (UnsupportedEncodingException e)
+ {
+ e.printStackTrace(); // as if
+ }
+ }
+ transcript.createDatasetSequence();
+
+ al.addSequence(transcript);
+
+ /*
+ * transfer features to the new sequence; we use EnsemblCdna to do this,
+ * to filter out unwanted features types (see method retainFeature)
+ */
+ List<int[]> mapTo = new ArrayList<int[]>();
+ mapTo.add(new int[] { 1, transcriptLength });
+ MapList mapping = new MapList(mappedFrom, mapTo, 1, 1);
+ EnsemblCdna cdna = new EnsemblCdna(getDomain());
+ cdna.transferFeatures(gene.getSequenceFeatures(),
+ transcript.getDatasetSequence(), mapping, parentId);
+
+ /*
+ * fetch and save cross-references
+ */
+ cdna.getCrossReferences(transcript);
+
+ /*
+ * and finally fetch the protein product and save as a cross-reference
+ */
+ cdna.addProteinProduct(transcript);
+
+ return transcript;
+ }
+
+ /**
+ * Returns the 'transcript_id' property of the sequence feature (or null)
+ *
+ * @param feature
+ * @return
+ */
+ protected String getTranscriptId(SequenceFeature feature)
+ {
+ return (String) feature.getValue("transcript_id");
+ }
+
+ /**
+ * Returns a list of the transcript features on the sequence whose Parent is
+ * the gene for the accession id.
+ *
+ * @param accId
+ * @param geneSequence
+ * @return
+ */
+ protected List<SequenceFeature> getTranscriptFeatures(String accId,
+ SequenceI geneSequence)
+ {
+ List<SequenceFeature> transcriptFeatures = new ArrayList<SequenceFeature>();
+
+ String parentIdentifier = GENE_PREFIX + accId;
+ SequenceFeature[] sfs = geneSequence.getSequenceFeatures();
+
+ if (sfs != null)
+ {
+ for (SequenceFeature sf : sfs)
+ {
+ if (isTranscript(sf.getType()))
+ {
+ String parent = (String) sf.getValue(PARENT);
+ if (parentIdentifier.equals(parent))
+ {
+ transcriptFeatures.add(sf);
+ }
+ }
+ }
+ }
+
+ return transcriptFeatures;
+ }
+
+ @Override
+ public String getDescription()
+ {
+ return "Fetches all transcripts and variant features for a gene or transcript";
+ }
+
+ /**
+ * Default test query is a gene id (can also enter a transcript id)
+ */
+ @Override
+ public String getTestQuery()
+ {
+ return "ENSG00000157764"; // BRAF, 5 transcripts, reverse strand
+ // ENSG00000090266 // NDUFB2, 15 transcripts, forward strand
+ // ENSG00000101812 // H2BFM histone, 3 transcripts, forward strand
+ // ENSG00000123569 // H2BFWT histone, 2 transcripts, reverse strand
+ }
+
+ /**
+ * Answers true for a feature of type 'gene' (or a sub-type of gene in the
+ * Sequence Ontology), whose ID is the accession we are retrieving
+ */
+ @Override
+ protected boolean identifiesSequence(SequenceFeature sf, String accId)
+ {
+ if (SequenceOntologyFactory.getInstance().isA(sf.getType(),
+ SequenceOntologyI.GENE))
+ {
+ String id = (String) sf.getValue(ID);
+ if ((GENE_PREFIX + accId).equals(id))
+ {
+ return true;
+ }
+ }
+ return false;
+ }
+
+ /**
+ * Answers true unless feature type is 'gene', or 'transcript' with a parent
+ * which is a different gene. We need the gene features to identify the range,
+ * but it is redundant information on the gene sequence. Checking the parent
+ * allows us to drop transcript features which belong to different
+ * (overlapping) genes.
+ */
+ @Override
+ protected boolean retainFeature(SequenceFeature sf, String accessionId)
+ {
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ String type = sf.getType();
+ if (so.isA(type, SequenceOntologyI.GENE))
+ {
+ return false;
+ }
+ if (isTranscript(type))
+ {
+ String parent = (String) sf.getValue(PARENT);
+ if (!(GENE_PREFIX + accessionId).equals(parent))
+ {
+ return false;
+ }
+ }
+ return true;
+ }
+
+ /**
+ * Answers false. This allows an optimisation - a single 'gene' feature is all
+ * that is needed to identify the positions of the gene on the genomic
+ * sequence.
+ */
+ @Override
+ protected boolean isSpliceable()
+ {
+ return false;
+ }
+
+ @Override
+ protected List<String> getCrossReferenceDatabases()
+ {
+ // found these for ENSG00000157764 on 30/01/2016:
+ // return new String[] {"Vega_gene", "OTTG", "ENS_LRG_gene", "ArrayExpress",
+ // "EntrezGene", "HGNC", "MIM_GENE", "MIM_MORBID", "WikiGene"};
+ return CROSS_REFERENCES;
+ }
+
+ /**
+ * Override to do nothing as Ensembl doesn't return a protein sequence for a
+ * gene identifier
+ */
+ @Override
+ protected void addProteinProduct(SequenceI querySeq)
+ {
+ }
+
+ @Override
+ public Regex getAccessionValidator()
+ {
+ return ACCESSION_REGEX;
+ }
+
+ /**
+ * Returns a descriptor for suitable feature display settings with
+ * <ul>
+ * <li>only exon or sequence_variant features (or their subtypes in the
+ * Sequence Ontology) visible</li>
+ * <li>variant features coloured red</li>
+ * <li>exon features coloured by label (exon name)</li>
+ * <li>variants displayed above (on top of) exons</li>
+ * </ul>
+ */
+ @Override
+ public FeatureSettingsModelI getFeatureColourScheme()
+ {
+ return new FeatureSettingsAdapter()
+ {
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ @Override
+ public boolean isFeatureDisplayed(String type)
+ {
+ return (so.isA(type, SequenceOntologyI.EXON) || so.isA(type,
+ SequenceOntologyI.SEQUENCE_VARIANT));
+ }
+
+ @Override
+ public FeatureColourI getFeatureColour(String type)
+ {
+ if (so.isA(type, SequenceOntologyI.EXON))
+ {
+ return new FeatureColourAdapter()
+ {
+ @Override
+ public boolean isColourByLabel()
+ {
+ return true;
+ }
+ };
+ }
+ if (so.isA(type, SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ return new FeatureColourAdapter()
+ {
+
+ @Override
+ public Color getColour()
+ {
+ return Color.RED;
+ }
+ };
+ }
+ return null;
+ }
+
+ /**
+ * order to render sequence_variant after exon after the rest
+ */
+ @Override
+ public int compare(String feature1, String feature2)
+ {
+ if (so.isA(feature1, SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ return +1;
+ }
+ if (so.isA(feature2, SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ return -1;
+ }
+ if (so.isA(feature1, SequenceOntologyI.EXON))
+ {
+ return +1;
+ }
+ if (so.isA(feature2, SequenceOntologyI.EXON))
+ {
+ return -1;
+ }
+ return 0;
+ }
+ };
+ }
+
+}
git://source.jalview.org / jalview.git / blobdiff