/*
* 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 .
* The Jalview Authors are detailed in the 'AUTHORS' file.
*/
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.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
*
* @author gmcarstairs
*/
public class EnsemblGene extends EnsemblSeqProxy
{
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.
* Method:
*
* - resolves a transcript identifier by looking up its parent gene id
* - resolves an external identifier by looking up xref-ed gene ids
* - fetches the gene sequence
* - fetches features on the sequence
* - identifies "transcript" features whose Parent is the requested gene
* - fetches the transcript sequence for each transcript
* - makes a mapping from the gene to each transcript
* - copies features from gene to transcript sequences
* - fetches the protein sequence for each transcript, maps and saves it as
* a cross-reference
* - aligns each transcript against the gene sequence based on the position
* mappings
*
*
* @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
{
/*
* convert to a non-duplicated list of gene identifiers
*/
List geneIds = getGeneIds(query);
AlignmentI al = null;
for (String geneId : geneIds)
{
/*
* fetch the gene sequence(s) with features and xrefs
*/
AlignmentI geneAlignment = super.getSequenceRecords(geneId);
if (geneAlignment == null)
{
continue;
}
if (geneAlignment.getHeight() == 1)
{
getTranscripts(geneAlignment, geneId);
}
if (al == null)
{
al = geneAlignment;
}
else
{
al.append(geneAlignment);
}
}
return al;
}
/**
* Converts a query, which may contain one or more gene or transcript
* identifiers, into a non-redundant list of gene identifiers.
*
* @param accessions
* @return
*/
List getGeneIds(String accessions)
{
List geneIds = new ArrayList();
for (String acc : accessions.split(getAccessionSeparator()))
{
if (isGeneIdentifier(acc))
{
if (!geneIds.contains(acc))
{
geneIds.add(acc);
}
}
/*
* if given a transcript id, look up its gene parent
*/
else if (isTranscriptIdentifier(acc))
{
String geneId = new EnsemblLookup(getDomain()).getParent(acc);
if (geneId != null && !geneIds.contains(geneId))
{
geneIds.add(geneId);
}
}
else if (isProteinIdentifier(acc))
{
String tscriptId = new EnsemblLookup(getDomain()).getParent(acc);
if (tscriptId != null)
{
String geneId = new EnsemblLookup(getDomain())
.getParent(tscriptId);
if (geneId != null && !geneIds.contains(geneId))
{
geneIds.add(geneId);
}
}
// NOTE - acc is lost if it resembles an ENS.+ ID but isn't actually
// resolving to one... e.g. ENSMICP00000009241
}
/*
* if given a gene or other external name, lookup and fetch
* the corresponding gene for all model organisms
*/
else
{
List ids = new EnsemblSymbol(getDomain(), getDbSource(),
getDbVersion()).getIds(acc);
for (String geneId : ids)
{
if (!geneIds.contains(geneId))
{
geneIds.add(geneId);
}
}
}
}
return geneIds;
}
/**
* 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 ids = new EnsemblSymbol(getDomain(), getDbSource(),
getDbVersion()).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 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)
{
/*
* 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 sfs = gene.getFeatures().getFeaturesByOntology(
soTerms);
for (SequenceFeature sf : sfs)
{
gene.deleteFeature(sf);
}
}
/**
* 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 splices = findFeatures(gene,
SequenceOntologyI.EXON, parentId);
if (splices.isEmpty())
{
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 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 = (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 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);
/*
* 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 getTranscriptFeatures(String accId,
SequenceI geneSequence)
{
List transcriptFeatures = new ArrayList();
String parentIdentifier = GENE_PREFIX + accId;
// todo optimise here by transcript type!
List sfs = geneSequence.getFeatures()
.getPositionalFeatures();
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 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
*
* - only exon or sequence_variant features (or their subtypes in the
* Sequence Ontology) visible
* - variant features coloured red
* - exon features coloured by label (exon name)
* - variants displayed above (on top of) exons
*
*/
@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 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;
}
};
}
}