1 package jalview.ext.ensembl;
3 import jalview.api.FeatureColourI;
4 import jalview.api.FeatureSettingsModelI;
5 import jalview.datamodel.AlignmentI;
6 import jalview.datamodel.Sequence;
7 import jalview.datamodel.SequenceFeature;
8 import jalview.datamodel.SequenceI;
9 import jalview.io.gff.SequenceOntologyFactory;
10 import jalview.io.gff.SequenceOntologyI;
11 import jalview.schemes.FeatureColour;
12 import jalview.schemes.FeatureSettingsAdapter;
13 import jalview.util.MapList;
15 import java.awt.Color;
16 import java.io.UnsupportedEncodingException;
17 import java.net.URLDecoder;
18 import java.util.ArrayList;
19 import java.util.Arrays;
20 import java.util.List;
22 import com.stevesoft.pat.Regex;
25 * A class that fetches genomic sequence and all transcripts for an Ensembl gene
29 public class EnsemblGene extends EnsemblSeqProxy
31 private static final String GENE_PREFIX = "gene:";
34 * accepts anything as we will attempt lookup of gene or
35 * transcript id or gene name
37 private static final Regex ACCESSION_REGEX = new Regex(".*");
39 private static final EnsemblFeatureType[] FEATURES_TO_FETCH = {
40 EnsemblFeatureType.gene, EnsemblFeatureType.transcript,
41 EnsemblFeatureType.exon, EnsemblFeatureType.cds,
42 EnsemblFeatureType.variation };
45 * Default constructor (to use rest.ensembl.org)
53 * Constructor given the target domain to fetch data from
57 public EnsemblGene(String d)
63 public String getDbName()
69 protected EnsemblFeatureType[] getFeaturesToFetch()
71 return FEATURES_TO_FETCH;
75 protected EnsemblSeqType getSourceEnsemblType()
77 return EnsemblSeqType.GENOMIC;
81 * Returns an alignment containing the gene(s) for the given gene or
82 * transcript identifier, or external identifier (e.g. Uniprot id). If given a
83 * gene name or external identifier, returns any related gene sequences found
84 * for model organisms. If only a single gene is queried for, then its
85 * transcripts are also retrieved and added to the alignment. <br>
88 * <li>resolves a transcript identifier by looking up its parent gene id</li>
89 * <li>resolves an external identifier by looking up xref-ed gene ids</li>
90 * <li>fetches the gene sequence</li>
91 * <li>fetches features on the sequence</li>
92 * <li>identifies "transcript" features whose Parent is the requested gene</li>
93 * <li>fetches the transcript sequence for each transcript</li>
94 * <li>makes a mapping from the gene to each transcript</li>
95 * <li>copies features from gene to transcript sequences</li>
96 * <li>fetches the protein sequence for each transcript, maps and saves it as
97 * a cross-reference</li>
98 * <li>aligns each transcript against the gene sequence based on the position
103 * a single gene or transcript identifier or gene name
104 * @return an alignment containing a gene, and possibly transcripts, or null
107 public AlignmentI getSequenceRecords(String query) throws Exception
110 * convert to a non-duplicated list of gene identifiers
112 List<String> geneIds = getGeneIds(query);
114 AlignmentI al = null;
115 for (String geneId : geneIds)
118 * fetch the gene sequence(s) with features and xrefs
120 AlignmentI geneAlignment = super.getSequenceRecords(geneId);
121 if (geneAlignment == null)
125 if (geneAlignment.getHeight() == 1)
127 getTranscripts(geneAlignment, geneId);
135 al.append(geneAlignment);
142 * Converts a query, which may contain one or more gene or transcript
143 * identifiers, into a non-redundant list of gene identifiers.
148 List<String> getGeneIds(String accessions)
150 List<String> geneIds = new ArrayList<String>();
152 for (String acc : accessions.split(getAccessionSeparator()))
154 if (isGeneIdentifier(acc))
156 if (!geneIds.contains(acc))
163 * if given a transcript id, look up its gene parent
165 else if (isTranscriptIdentifier(acc))
167 String geneId = new EnsemblLookup(getDomain()).getParent(acc);
168 if (geneId != null && !geneIds.contains(geneId))
175 * if given a gene or other external name, lookup and fetch
176 * the corresponding gene for all model organisms
180 List<String> ids = new EnsemblSymbol(getDomain(), getDbSource(),
181 getDbVersion()).getIds(acc);
182 for (String geneId : ids)
184 if (!geneIds.contains(geneId))
195 * Attempts to get Ensembl stable identifiers for model organisms for a gene
196 * name by calling the xrefs symbol REST service to resolve the gene name.
201 protected String getGeneIdentifiersForName(String query)
203 List<String> ids = new EnsemblSymbol(getDomain(), getDbSource(),
204 getDbVersion()).getIds(query);
207 for (String id : ids)
209 if (isGeneIdentifier(id))
219 * Constructs all transcripts for the gene, as identified by "transcript"
220 * features whose Parent is the requested gene. The coding transcript
221 * sequences (i.e. with introns omitted) are added to the alignment.
227 protected void getTranscripts(AlignmentI al, String accId)
230 SequenceI gene = al.getSequenceAt(0);
231 List<SequenceFeature> transcriptFeatures = getTranscriptFeatures(accId,
234 for (SequenceFeature transcriptFeature : transcriptFeatures)
236 makeTranscript(transcriptFeature, al, gene);
239 clearGeneFeatures(gene);
243 * Remove unwanted features (transcript, exon, CDS) from the gene sequence
244 * after we have used them to derive transcripts and transfer features
248 protected void clearGeneFeatures(SequenceI gene)
250 SequenceFeature[] sfs = gene.getSequenceFeatures();
253 SequenceOntologyI so = SequenceOntologyFactory.getInstance();
254 List<SequenceFeature> filtered = new ArrayList<SequenceFeature>();
255 for (SequenceFeature sf : sfs)
257 String type = sf.getType();
258 if (!isTranscript(type) && !so.isA(type, SequenceOntologyI.EXON)
259 && !so.isA(type, SequenceOntologyI.CDS))
264 gene.setSequenceFeatures(filtered
265 .toArray(new SequenceFeature[filtered.size()]));
270 * Constructs a spliced transcript sequence by finding 'exon' features for the
271 * given id (or failing that 'CDS'). Copies features on to the new sequence.
272 * 'Aligns' the new sequence against the gene sequence by padding with gaps,
273 * and adds it to the alignment.
275 * @param transcriptFeature
277 * the alignment to which to add the new sequence
279 * the parent gene sequence, with features
282 SequenceI makeTranscript(SequenceFeature transcriptFeature,
283 AlignmentI al, SequenceI gene)
285 String accId = getTranscriptId(transcriptFeature);
292 * NB we are mapping from gene sequence (not genome), so do not
293 * need to check for reverse strand (gene and transcript sequences
294 * are in forward sense)
298 * make a gene-length sequence filled with gaps
299 * we will fill in the bases for transcript regions
301 char[] seqChars = new char[gene.getLength()];
302 Arrays.fill(seqChars, al.getGapCharacter());
305 * look for exon features of the transcript, failing that for CDS
306 * (for example ENSG00000124610 has 1 CDS but no exon features)
308 String parentId = "transcript:" + accId;
309 List<SequenceFeature> splices = findFeatures(gene,
310 SequenceOntologyI.EXON, parentId);
311 if (splices.isEmpty())
313 splices = findFeatures(gene, SequenceOntologyI.CDS, parentId);
316 int transcriptLength = 0;
317 final char[] geneChars = gene.getSequence();
318 int offset = gene.getStart(); // to convert to 0-based positions
319 List<int[]> mappedFrom = new ArrayList<int[]>();
321 for (SequenceFeature sf : splices)
323 int start = sf.getBegin() - offset;
324 int end = sf.getEnd() - offset;
325 int spliceLength = end - start + 1;
326 System.arraycopy(geneChars, start, seqChars, start, spliceLength);
327 transcriptLength += spliceLength;
328 mappedFrom.add(new int[] { sf.getBegin(), sf.getEnd() });
331 Sequence transcript = new Sequence(accId, seqChars, 1, transcriptLength);
334 * Ensembl has gene name as transcript Name
335 * EnsemblGenomes doesn't, but has a url-encoded description field
337 String description = (String) transcriptFeature.getValue(NAME);
338 if (description == null)
340 description = (String) transcriptFeature.getValue(DESCRIPTION);
342 if (description != null)
346 transcript.setDescription(URLDecoder.decode(description, "UTF-8"));
347 } catch (UnsupportedEncodingException e)
349 e.printStackTrace(); // as if
352 transcript.createDatasetSequence();
354 al.addSequence(transcript);
357 * transfer features to the new sequence; we use EnsemblCdna to do this,
358 * to filter out unwanted features types (see method retainFeature)
360 List<int[]> mapTo = new ArrayList<int[]>();
361 mapTo.add(new int[] { 1, transcriptLength });
362 MapList mapping = new MapList(mappedFrom, mapTo, 1, 1);
363 EnsemblCdna cdna = new EnsemblCdna(getDomain());
364 cdna.transferFeatures(gene.getSequenceFeatures(),
365 transcript.getDatasetSequence(), mapping, parentId);
368 * fetch and save cross-references
370 cdna.getCrossReferences(transcript);
373 * and finally fetch the protein product and save as a cross-reference
375 cdna.addProteinProduct(transcript);
381 * Returns the 'transcript_id' property of the sequence feature (or null)
386 protected String getTranscriptId(SequenceFeature feature)
388 return (String) feature.getValue("transcript_id");
392 * Returns a list of the transcript features on the sequence whose Parent is
393 * the gene for the accession id.
396 * @param geneSequence
399 protected List<SequenceFeature> getTranscriptFeatures(String accId,
400 SequenceI geneSequence)
402 List<SequenceFeature> transcriptFeatures = new ArrayList<SequenceFeature>();
404 String parentIdentifier = GENE_PREFIX + accId;
405 SequenceFeature[] sfs = geneSequence.getSequenceFeatures();
409 for (SequenceFeature sf : sfs)
411 if (isTranscript(sf.getType()))
413 String parent = (String) sf.getValue(PARENT);
414 if (parentIdentifier.equals(parent))
416 transcriptFeatures.add(sf);
422 return transcriptFeatures;
426 public String getDescription()
428 return "Fetches all transcripts and variant features for a gene or transcript";
432 * Default test query is a gene id (can also enter a transcript id)
435 public String getTestQuery()
437 return "ENSG00000157764"; // BRAF, 5 transcripts, reverse strand
438 // ENSG00000090266 // NDUFB2, 15 transcripts, forward strand
439 // ENSG00000101812 // H2BFM histone, 3 transcripts, forward strand
440 // ENSG00000123569 // H2BFWT histone, 2 transcripts, reverse strand
444 * Answers true for a feature of type 'gene' (or a sub-type of gene in the
445 * Sequence Ontology), whose ID is the accession we are retrieving
448 protected boolean identifiesSequence(SequenceFeature sf, String accId)
450 if (SequenceOntologyFactory.getInstance().isA(sf.getType(),
451 SequenceOntologyI.GENE))
453 String id = (String) sf.getValue(ID);
454 if ((GENE_PREFIX + accId).equals(id))
463 * Answers true unless feature type is 'gene', or 'transcript' with a parent
464 * which is a different gene. We need the gene features to identify the range,
465 * but it is redundant information on the gene sequence. Checking the parent
466 * allows us to drop transcript features which belong to different
467 * (overlapping) genes.
470 protected boolean retainFeature(SequenceFeature sf, String accessionId)
472 SequenceOntologyI so = SequenceOntologyFactory.getInstance();
473 String type = sf.getType();
474 if (so.isA(type, SequenceOntologyI.GENE))
478 if (isTranscript(type))
480 String parent = (String) sf.getValue(PARENT);
481 if (!(GENE_PREFIX + accessionId).equals(parent))
490 * Answers false. This allows an optimisation - a single 'gene' feature is all
491 * that is needed to identify the positions of the gene on the genomic
495 protected boolean isSpliceable()
501 * Override to do nothing as Ensembl doesn't return a protein sequence for a
505 protected void addProteinProduct(SequenceI querySeq)
510 public Regex getAccessionValidator()
512 return ACCESSION_REGEX;
516 * Returns a descriptor for suitable feature display settings with
518 * <li>only exon or sequence_variant features (or their subtypes in the
519 * Sequence Ontology) visible</li>
520 * <li>variant features coloured red</li>
521 * <li>exon features coloured by label (exon name)</li>
522 * <li>variants displayed above (on top of) exons</li>
526 public FeatureSettingsModelI getFeatureColourScheme()
528 return new FeatureSettingsAdapter()
530 SequenceOntologyI so = SequenceOntologyFactory.getInstance();
533 public boolean isFeatureDisplayed(String type)
535 return (so.isA(type, SequenceOntologyI.EXON) || so.isA(type,
536 SequenceOntologyI.SEQUENCE_VARIANT));
540 public FeatureColourI getFeatureColour(String type)
542 if (so.isA(type, SequenceOntologyI.EXON))
544 return new FeatureColour()
547 public boolean isColourByLabel()
553 if (so.isA(type, SequenceOntologyI.SEQUENCE_VARIANT))
555 return new FeatureColour()
559 public Color getColour()
569 * order to render sequence_variant after exon after the rest
572 public int compare(String feature1, String feature2)
574 if (so.isA(feature1, SequenceOntologyI.SEQUENCE_VARIANT))
578 if (so.isA(feature2, SequenceOntologyI.SEQUENCE_VARIANT))
582 if (so.isA(feature1, SequenceOntologyI.EXON))
586 if (so.isA(feature2, SequenceOntologyI.EXON))