+/*
+ * Jalview - A Sequence Alignment Editor and Viewer ($$Version-Rel$$)
+ * Copyright (C) $$Year-Rel$$ The Jalview Authors
+ *
+ * This file is part of Jalview.
+ *
+ * Jalview is free software: you can redistribute it and/or
+ * modify it under the terms of the GNU General Public License
+ * as published by the Free Software Foundation, either version 3
+ * of the License, or (at your option) any later version.
+ *
+ * Jalview is distributed in the hope that it will be useful, but
+ * WITHOUT ANY WARRANTY; without even the implied warranty
+ * of MERCHANTABILITY or FITNESS FOR A PARTICULAR
+ * PURPOSE. See the GNU General Public License for more details.
+ *
+ * You should have received a copy of the GNU General Public License
+ * along with Jalview. If not, see <http://www.gnu.org/licenses/>.
+ * The Jalview Authors are detailed in the 'AUTHORS' file.
+ */
package jalview.ext.ensembl;
-import jalview.datamodel.AlignedCodonFrame;
+import jalview.api.FeatureColourI;
+import jalview.api.FeatureSettingsModelI;
import jalview.datamodel.AlignmentI;
+import jalview.datamodel.GeneLociI;
+import jalview.datamodel.Sequence;
import jalview.datamodel.SequenceFeature;
import jalview.datamodel.SequenceI;
-import jalview.io.gff.SequenceOntology;
+import jalview.datamodel.features.SequenceFeatures;
+import jalview.io.gff.SequenceOntologyFactory;
+import jalview.io.gff.SequenceOntologyI;
+import jalview.schemes.FeatureColour;
+import jalview.schemes.FeatureSettingsAdapter;
import jalview.util.MapList;
+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
*
*/
public class EnsemblGene extends EnsemblSeqProxy
{
+ /*
+ * 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 };
+ private static final String CHROMOSOME = "chromosome";
+
+ /**
+ * 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 (GENE)";
+ return "ENSEMBL";
}
@Override
return EnsemblSeqType.GENOMIC;
}
+ @Override
+ protected String getObjectType()
+ {
+ return OBJECT_TYPE_GENE;
+ }
+
/**
- * Builds an alignment of all transcripts for the requested gene:
+ * 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>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>aligns each transcript against the gene sequence based on the position
* mappings</li>
* </ul>
+ *
+ * @param query
+ * a single gene or transcript identifier or gene name
+ * @return an alignment containing a gene, and possibly transcripts, or null
*/
@Override
public AlignmentI getSequenceRecords(String query) throws Exception
{
- AlignmentI al = super.getSequenceRecords(query);
- if (al.getHeight() > 0)
+ /*
+ * convert to a non-duplicated list of gene identifiers
+ */
+ List<String> geneIds = getGeneIds(query);
+
+ AlignmentI al = null;
+ for (String geneId : geneIds)
{
- getTranscripts(al, query);
- }
+ /*
+ * fetch the gene sequence(s) with features and xrefs
+ */
+ AlignmentI geneAlignment = super.getSequenceRecords(geneId);
+ if (geneAlignment == null)
+ {
+ continue;
+ }
+
+ if (geneAlignment.getHeight() == 1)
+ {
+ // ensure id has 'correct' case for the Ensembl identifier
+ geneId = geneAlignment.getSequenceAt(0).getName();
+
+ findGeneLoci(geneAlignment.getSequenceAt(0), geneId);
+ getTranscripts(geneAlignment, geneId);
+ }
+ if (al == null)
+ {
+ al = geneAlignment;
+ }
+ else
+ {
+ al.append(geneAlignment);
+ }
+ }
return al;
}
/**
- * Find and fetch all transcripts for the gene, as identified by "transcript"
- * features whose Parent is the requested gene
+ * Calls the /lookup/id REST service, parses the response for gene
+ * coordinates, and if successful, adds these to the sequence. If this fails,
+ * fall back on trying to parse the sequence description in case it is in
+ * Ensembl-gene format e.g. chromosome:GRCh38:17:45051610:45109016:1.
+ *
+ * @param seq
+ * @param geneId
+ */
+ void findGeneLoci(SequenceI seq, String geneId)
+ {
+ GeneLociI geneLoci = new EnsemblLookup(getDomain()).getGeneLoci(geneId);
+ if (geneLoci != null)
+ {
+ seq.setGeneLoci(geneLoci.getSpeciesId(), geneLoci.getAssemblyId(),
+ geneLoci.getChromosomeId(), geneLoci.getMapping());
+ }
+ else
+ {
+ parseChromosomeLocations(seq);
+ }
+ }
+
+ /**
+ * Parses and saves fields of an Ensembl-style description e.g.
+ * chromosome:GRCh38:17:45051610:45109016:1
+ *
+ * @param seq
+ */
+ boolean parseChromosomeLocations(SequenceI seq)
+ {
+ String description = seq.getDescription();
+ if (description == null)
+ {
+ return false;
+ }
+ String[] tokens = description.split(":");
+ if (tokens.length == 6 && tokens[0].startsWith(CHROMOSOME))
+ {
+ String ref = tokens[1];
+ String chrom = tokens[2];
+ try
+ {
+ int chStart = Integer.parseInt(tokens[3]);
+ int chEnd = Integer.parseInt(tokens[4]);
+ boolean forwardStrand = "1".equals(tokens[5]);
+ String species = ""; // not known here
+ int[] from = new int[] { seq.getStart(), seq.getEnd() };
+ int[] to = new int[] { forwardStrand ? chStart : chEnd,
+ forwardStrand ? chEnd : chStart };
+ MapList map = new MapList(from, to, 1, 1);
+ seq.setGeneLoci(species, ref, chrom, map);
+ return true;
+ } catch (NumberFormatException e)
+ {
+ System.err.println("Bad integers in description " + description);
+ }
+ }
+ return false;
+ }
+
+ /**
+ * Converts a query, which may contain one or more gene, transcript, or
+ * external (to Ensembl) identifiers, into a non-redundant list of gene
+ * identifiers.
+ *
+ * @param accessions
+ * @return
+ */
+ List<String> getGeneIds(String accessions)
+ {
+ List<String> geneIds = new ArrayList<>();
+
+ for (String acc : accessions.split(getAccessionSeparator()))
+ {
+ /*
+ * First try lookup as an Ensembl (gene or transcript) identifier
+ */
+ String geneId = new EnsemblLookup(getDomain()).getGeneId(acc);
+ if (geneId != null)
+ {
+ if (!geneIds.contains(geneId))
+ {
+ geneIds.add(geneId);
+ }
+ }
+ else
+ {
+ /*
+ * if given a gene or other external name, lookup and fetch
+ * the corresponding gene for all model organisms
+ */
+ List<String> ids = new EnsemblSymbol(getDomain(), getDbSource(),
+ getDbVersion()).getGeneIds(acc);
+ for (String id : ids)
+ {
+ if (!geneIds.contains(id))
+ {
+ geneIds.add(id);
+ }
+ }
+ }
+ }
+ return geneIds;
+ }
+
+ /**
+ * 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
{
SequenceI gene = al.getSequenceAt(0);
- List<String> transcriptIds = getTranscriptIds(accId, gene);
+ List<SequenceFeature> transcriptFeatures = getTranscriptFeatures(accId,
+ gene);
- // TODO: could just use features and genomic sequence
- // to generate the transcript sequences - faster
- // could also grab "Name" as transcript description (gene name)
- for (String transcriptId : transcriptIds)
+ for (SequenceFeature transcriptFeature : transcriptFeatures)
{
- /*
- * fetch and map the transcript sequence; we can pass in the gene
- * sequence with features marked to save fetching it again
- */
- EnsemblCdna cdnaFetcher = new EnsemblCdna();
- AlignmentI al2 = cdnaFetcher.getSequenceRecords(transcriptId,
- gene);
- for (SequenceI seq : al2.getSequences())
- {
- /*
- * build mapping from gene sequence to transcript
- */
- MapList mapping = cdnaFetcher.getGenomicRanges(gene, transcriptId,
- seq.getStart());
+ makeTranscript(transcriptFeature, al, gene);
+ }
- /*
- * align the transcript to the gene
- */
- AlignedCodonFrame acf = new AlignedCodonFrame();
- acf.addMap(gene, seq, mapping);
- char gap = al.getGapCharacter();
- // AlignmentUtils.alignSequenceAs(seq, gene, acf, String.valueOf(gap),
- // gap, false, false);
+ clearGeneFeatures(gene);
+ }
- al.addSequence(seq);
- }
+ /**
+ * 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)
+ {
+ /*
+ * Note we include NMD_transcript_variant here because it behaves like
+ * 'transcript' in Ensembl, although strictly speaking it is not
+ * (it is a sub-type of sequence_variant)
+ */
+ String[] soTerms = new String[] {
+ SequenceOntologyI.NMD_TRANSCRIPT_VARIANT,
+ SequenceOntologyI.TRANSCRIPT, SequenceOntologyI.EXON,
+ SequenceOntologyI.CDS };
+ List<SequenceFeature> sfs = gene.getFeatures().getFeaturesByOntology(
+ soTerms);
+ for (SequenceFeature sf : sfs)
+ {
+ gene.deleteFeature(sf);
}
}
/**
- * Returns a list of the ids of transcript features on the sequence whose
- * Parent is the gene for the accession id
+ * 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 accId
- * @param geneSequence
+ * @param transcriptFeature
+ * @param al
+ * the alignment to which to add the new sequence
+ * @param gene
+ * the parent gene sequence, with features
* @return
*/
- protected List<String> getTranscriptIds(String accId, SequenceI geneSequence)
+ SequenceI makeTranscript(SequenceFeature transcriptFeature, AlignmentI al,
+ SequenceI gene)
{
- SequenceOntology so = SequenceOntology.getInstance();
- List<String> transcriptIds = new ArrayList<String>();
+ String accId = getTranscriptId(transcriptFeature);
+ if (accId == null)
+ {
+ return null;
+ }
/*
- * scan for transcript features belonging to our gene;
- * also remove any which belong to other genes
+ * 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)
*/
- SequenceFeature[] sfs = geneSequence.getSequenceFeatures();
- List<SequenceFeature> keptFeatures = new ArrayList<SequenceFeature>();
- boolean featureDropped = false;
- String parentIdentifier = "gene:" + accId;
- for (SequenceFeature sf : sfs)
+
+ /*
+ * 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 = accId;
+ List<SequenceFeature> splices = findFeatures(gene,
+ SequenceOntologyI.EXON, parentId);
+ if (splices.isEmpty())
{
- if (so.isA(sf.getType(), SequenceOntology.TRANSCRIPT))
+ splices = findFeatures(gene, SequenceOntologyI.CDS, parentId);
+ }
+ SequenceFeatures.sortFeatures(splices, true);
+
+ int transcriptLength = 0;
+ final char[] geneChars = gene.getSequence();
+ int offset = gene.getStart(); // to convert to 0-based positions
+ List<int[]> mappedFrom = new ArrayList<>();
+
+ 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 = transcriptFeature.getDescription();
+ if (description == null)
+ {
+ description = (String) transcriptFeature.getValue(DESCRIPTION);
+ }
+ if (description != null)
+ {
+ try
{
- String parent = (String) sf.getValue(PARENT);
- if (parentIdentifier.equals(parent))
- {
- transcriptIds.add((String) sf.getValue("transcript_id"));
- keptFeatures.add(sf);
- }
- else
- {
- featureDropped = true;
- }
- }
- else
+ transcript.setDescription(URLDecoder.decode(description, "UTF-8"));
+ } catch (UnsupportedEncodingException e)
{
- keptFeatures.add(sf);
+ e.printStackTrace(); // as if
}
}
- if (featureDropped)
+ 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<>();
+ mapTo.add(new int[] { 1, transcriptLength });
+ MapList mapping = new MapList(mappedFrom, mapTo, 1, 1);
+ EnsemblCdna cdna = new EnsemblCdna(getDomain());
+ cdna.transferFeatures(gene.getFeatures().getPositionalFeatures(),
+ transcript.getDatasetSequence(), mapping, parentId);
+
+ mapTranscriptToChromosome(transcript, gene, mapping);
+
+ /*
+ * 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;
+ }
+
+ /**
+ * If the gene has a mapping to chromosome coordinates, derive the transcript
+ * chromosome regions and save on the transcript sequence
+ *
+ * @param transcript
+ * @param gene
+ * @param mapping
+ * the mapping from gene to transcript positions
+ */
+ protected void mapTranscriptToChromosome(SequenceI transcript,
+ SequenceI gene, MapList mapping)
+ {
+ GeneLociI loci = gene.getGeneLoci();
+ if (loci == null)
+ {
+ return;
+ }
+
+ MapList geneMapping = loci.getMapping();
+
+ List<int[]> exons = mapping.getFromRanges();
+ List<int[]> transcriptLoci = new ArrayList<>();
+
+ for (int[] exon : exons)
{
- geneSequence.getDatasetSequence().setSequenceFeatures(
- keptFeatures.toArray(new SequenceFeature[keptFeatures
- .size()]));
+ transcriptLoci.add(geneMapping.locateInTo(exon[0], exon[1]));
}
- return transcriptIds;
+
+ List<int[]> transcriptRange = Arrays.asList(new int[] {
+ transcript.getStart(), transcript.getEnd() });
+ MapList mapList = new MapList(transcriptRange, transcriptLoci, 1, 1);
+
+ transcript.setGeneLoci(loci.getSpeciesId(), loci.getAssemblyId(),
+ loci.getChromosomeId(), mapList);
+ }
+
+ /**
+ * Returns the 'transcript_id' property of the sequence feature (or null)
+ *
+ * @param feature
+ * @return
+ */
+ protected String getTranscriptId(SequenceFeature feature)
+ {
+ return (String) feature.getValue(JSON_ID);
+ }
+
+ /**
+ * Returns a list of the transcript features on the sequence whose Parent is
+ * the gene for the accession id.
+ * <p>
+ * Transcript features are those of type "transcript", or any of its sub-types
+ * in the Sequence Ontology e.g. "mRNA", "processed_transcript". We also
+ * include "NMD_transcript_variant", because this type behaves like a
+ * transcript identifier in Ensembl, although strictly speaking it is not in
+ * the SO.
+ *
+ * @param accId
+ * @param geneSequence
+ * @return
+ */
+ protected List<SequenceFeature> getTranscriptFeatures(String accId,
+ SequenceI geneSequence)
+ {
+ List<SequenceFeature> transcriptFeatures = new ArrayList<>();
+
+ String parentIdentifier = accId;
+
+ List<SequenceFeature> sfs = geneSequence.getFeatures()
+ .getFeaturesByOntology(SequenceOntologyI.TRANSCRIPT);
+ sfs.addAll(geneSequence.getFeatures().getPositionalFeatures(
+ SequenceOntologyI.NMD_TRANSCRIPT_VARIANT));
+
+ for (SequenceFeature sf : sfs)
+ {
+ String parent = (String) sf.getValue(PARENT);
+ if (parentIdentifier.equalsIgnoreCase(parent))
+ {
+ transcriptFeatures.add(sf);
+ }
+ }
+
+ return transcriptFeatures;
}
@Override
public String getDescription()
{
- return "Fetches all transcripts and variant features for a gene";
+ return "Fetches all transcripts and variant features for a gene or transcript";
}
/**
- * Default test query is a transcript
+ * Default test query is a gene id (can also enter a transcript id)
*/
@Override
public String getTestQuery()
{
- return "ENSG00000157764"; // reverse strand
- // ENSG00000090266 // forward strand
+ 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
+ * Answers a list of sequence features (if any) whose type is 'gene' (or a
+ * subtype of gene in the Sequence Ontology), and whose ID is the accession we
+ * are retrieving
*/
@Override
- protected boolean identifiesSequence(SequenceFeature sf, String accId)
+ protected List<SequenceFeature> getIdentifyingFeatures(SequenceI seq,
+ String accId)
{
- if (SequenceOntology.getInstance().isA(sf.getType(),
- SequenceOntology.GENE))
+ List<SequenceFeature> result = new ArrayList<>();
+ List<SequenceFeature> sfs = seq.getFeatures()
+ .getFeaturesByOntology(SequenceOntologyI.GENE);
+ for (SequenceFeature sf : sfs)
{
- String id = (String) sf.getValue(ID);
- if (("gene:" + accId).equals(id))
+ String id = (String) sf.getValue(JSON_ID);
+ if (accId.equalsIgnoreCase(id))
{
- return true;
+ result.add(sf);
}
}
- return false;
+ return result;
}
/**
- * Answers true unless feature type is 'gene'. We need the gene features to
- * identify the range, but it is redundant information on the gene sequence.
+ * 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)
{
- return !SequenceOntology.getInstance().isA(sf.getType(),
- SequenceOntology.GENE);
+ 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 (!accessionId.equalsIgnoreCase(parent))
+ {
+ return false;
+ }
+ }
+ return true;
+ }
+
+ /**
+ * 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 isFeatureHidden(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 FeatureColour()
+ {
+ @Override
+ public boolean isColourByLabel()
+ {
+ return true;
+ }
+ };
+ }
+ if (so.isA(type, SequenceOntologyI.SEQUENCE_VARIANT))
+ {
+ return new FeatureColour()
+ {
+
+ @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