X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fext%2Fensembl%2FEnsemblSeqProxy.java;h=49e63418fee2929e656699c050ba396a3a8a0018;hb=6babd7c2387996384a49042ed4290095c13d5ed9;hp=4f85bd0058ce07b27237e32777f6aadcff41a162;hpb=409fd993c6e32e999b24082aae107a043a590f8f;p=jalview.git diff --git a/src/jalview/ext/ensembl/EnsemblSeqProxy.java b/src/jalview/ext/ensembl/EnsemblSeqProxy.java index 4f85bd0..49e6341 100644 --- a/src/jalview/ext/ensembl/EnsemblSeqProxy.java +++ b/src/jalview/ext/ensembl/EnsemblSeqProxy.java @@ -1,175 +1,569 @@ +/* + * 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.analysis.AlignmentUtils; +import jalview.analysis.Dna; +import jalview.bin.Cache; import jalview.datamodel.Alignment; import jalview.datamodel.AlignmentI; +import jalview.datamodel.DBRefEntry; +import jalview.datamodel.DBRefSource; +import jalview.datamodel.Mapping; +import jalview.datamodel.Sequence; +import jalview.datamodel.SequenceFeature; import jalview.datamodel.SequenceI; +import jalview.datamodel.features.SequenceFeatures; import jalview.exceptions.JalviewException; -import jalview.ext.ensembl.SeqFetcher.EnsemblSeqType; -import jalview.io.FastaFile; -import jalview.io.FileParse; +import jalview.io.gff.Gff3Helper; +import jalview.io.gff.SequenceOntologyFactory; +import jalview.io.gff.SequenceOntologyI; +import jalview.util.Comparison; import jalview.util.DBRefUtils; -import jalview.ws.seqfetcher.DbSourceProxyImpl; +import jalview.util.IntRangeComparator; +import jalview.util.MapList; +import jalview.util.Platform; +import java.io.IOException; +import java.net.MalformedURLException; +import java.net.URL; import java.util.ArrayList; import java.util.Arrays; +import java.util.Collections; import java.util.List; +import java.util.Map; -import com.stevesoft.pat.Regex; +import org.json.simple.parser.ParseException; -public abstract class EnsemblSeqProxy extends DbSourceProxyImpl +/** + * Base class for Ensembl sequence fetchers + * + * @see http://rest.ensembl.org/documentation/info/sequence_id + * @author gmcarstairs + */ +public abstract class EnsemblSeqProxy extends EnsemblRestClient { - SeqFetcher sf; + protected static final String DESCRIPTION = "description"; - public EnsemblSeqProxy() + /* + * enum for 'type' parameter to the /sequence REST service + */ + public enum EnsemblSeqType { - sf = new SeqFetcher(); - } + /** + * type=genomic to fetch full dna including introns + */ + GENOMIC("genomic"), - @Override - public String getDbSource() - { - return "ENSEMBL"; - } + /** + * type=cdna to fetch coding dna including UTRs + */ + CDNA("cdna"), + /** + * type=cds to fetch coding dna excluding UTRs + */ + CDS("cds"), - @Override - public String getDbVersion() - { - return "0"; // sf.getVersion(); - } + /** + * type=protein to fetch peptide product sequence + */ + PROTEIN("protein"); - @Override - public String getAccessionSeparator() - { - return " "; - } + /* + * the value of the 'type' parameter to fetch this version of + * an Ensembl sequence + */ + private String type; + + EnsemblSeqType(String t) + { + type = t; + } + + public String getType() + { + return type; + } - @Override - public Regex getAccessionValidator() - { - return new Regex("((ENSP|ENST|ENSG|CCDS)[0-9.]{3,})"); } /** - * Default test query is a transcript + * Default constructor (to use rest.ensembl.org) */ - @Override - public String getTestQuery() + public EnsemblSeqProxy() { - return "ENST00000288602"; + super(); } - @Override - public boolean isValidReference(String accession) + /** + * Constructor given the target domain to fetch data from + */ + public EnsemblSeqProxy(String d) { - return getAccessionValidator().search(accession); + super(d); } - private volatile boolean inProgress = false; - + /** + * Makes the sequence queries to Ensembl's REST service and returns an + * alignment consisting of the returned sequences. + */ @Override - public AlignmentI getSequenceRecords(String queries) throws Exception + public AlignmentI getSequenceRecords(String query) throws Exception { + // TODO use a String... query vararg instead? + + // 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 allIds = Arrays + .asList(query.split(getAccessionSeparator())); + AlignmentI alignment = null; inProgress = true; - List tids, ids = new ArrayList(); - tids = Arrays.asList(queries.split(" +")); - AlignmentI rtn = null; /* * execute queries, if necessary in batches of the * maximum allowed number of ids */ int maxQueryCount = getMaximumQueryCount(); - for (int v = 0, vSize = tids.size(); v < vSize; v += maxQueryCount) + for (int v = 0, vSize = allIds.size(); v < vSize; v += maxQueryCount) { int p = Math.min(vSize, v + maxQueryCount); - ids = tids.subList(v, p); + List ids = allIds.subList(v, p); try { - if (!sf.isEnsemblAvailable()) - { - inProgress = false; - throw new JalviewException("ENSEMBL Rest API not available."); - } - FileParse fp = new FileParse(sf.getSequenceReader( - getSourceEnsemblType(), ids)); - FastaFile fr = new FastaFile(fp); - if (fr.hasWarningMessage()) - { - System.out - .println("Warning when retrieving " + ids.size() + " ids" - + ids.toString() + "\n" + fr.getWarningMessage()); - } - else if (fr.getSeqs().size() != ids.size()) + alignment = fetchSequences(ids, alignment); + } catch (Throwable r) + { + inProgress = false; + String msg = "Aborting ID retrieval after " + v + + " chunks. Unexpected problem (" + r.getLocalizedMessage() + + ")"; + System.err.println(msg); + r.printStackTrace(); + break; + } + } + + if (alignment == null) + { + return null; + } + + /* + * fetch and transfer genomic sequence features, + * fetch protein product and add as cross-reference + */ + for (int i = 0, n = allIds.size(); i < n; i++) + { + addFeaturesAndProduct(allIds.get(i), alignment); + } + + List seqs = alignment.getSequences(); + for (int i = 0, n = seqs.size(); i < n; i++) + { + getCrossReferences(seqs.get(i)); + } + + return alignment; + } + + /** + * Fetches Ensembl features using the /overlap REST endpoint, and adds them to + * the sequence in the alignment. Also fetches the protein product, maps it + * from the CDS features of the sequence, and saves it as a cross-reference of + * the dna sequence. + * + * @param accId + * @param alignment + */ + protected void addFeaturesAndProduct(String accId, AlignmentI alignment) + { + if (alignment == null) + { + return; + } + + try + { + /* + * get 'dummy' genomic sequence with gene, transcript, + * exon, cds and variation features + */ + SequenceI genomicSequence = null; + EnsemblFeatures gffFetcher = new EnsemblFeatures(getDomain()); + EnsemblFeatureType[] features = getFeaturesToFetch(); + + Platform.timeCheck("ESP.getsequencerec1", Platform.TIME_MARK); + + + AlignmentI geneFeatures = gffFetcher.getSequenceRecords(accId, + features); + if (geneFeatures != null && geneFeatures.getHeight() > 0) + { + genomicSequence = geneFeatures.getSequenceAt(0); + } + + Platform.timeCheck("ESP.getsequencerec2", Platform.TIME_MARK); + + if (genomicSequence != null) + { + /* + * transfer features to the query sequence + */ + SequenceI querySeq = alignment.findName(accId, true); + if (transferFeatures(accId, genomicSequence, querySeq)) { - System.out.println("Only retrieved " + fr.getSeqs().size() - + " sequences for " + ids.size() + " query strings."); + + /* + * fetch and map protein product, and add it as a cross-reference + * of the retrieved sequence + */ + Platform.timeCheck("ESP.transferFeatures", Platform.TIME_MARK); + addProteinProduct(querySeq); } - if (fr.getSeqs().size() > 0) + } + } catch (IOException e) + { + System.err.println( + "Error transferring Ensembl features: " + e.getMessage()); + } + Platform.timeCheck("ESP.addfeat done", Platform.TIME_MARK); + } + + /** + * Returns those sequence feature types to fetch from Ensembl. We may want + * features either because they are of interest to the user, or as means to + * identify the locations of the sequence on the genomic sequence (CDS + * features identify CDS, exon features identify cDNA etc). + * + * @return + */ + protected abstract EnsemblFeatureType[] getFeaturesToFetch(); + + /** + * Fetches and maps the protein product, and adds it as a cross-reference of + * the retrieved sequence + */ + protected void addProteinProduct(SequenceI querySeq) + { + String accId = querySeq.getName(); + try + { + System.out.println("Adding protein product for " + accId); + AlignmentI protein = new EnsemblProtein(getDomain()) + .getSequenceRecords(accId); + if (protein == null || protein.getHeight() == 0) + { + System.out.println("No protein product found for " + accId); + return; + } + SequenceI proteinSeq = protein.getSequenceAt(0); + + /* + * need dataset sequences (to be the subject of mappings) + */ + proteinSeq.createDatasetSequence(); + querySeq.createDatasetSequence(); + + MapList mapList = AlignmentUtils.mapCdsToProtein(querySeq, + proteinSeq); + if (mapList != null) + { + // clunky: ensure Uniprot xref if we have one is on mapped sequence + SequenceI ds = proteinSeq.getDatasetSequence(); + // TODO: Verify ensp primary ref is on proteinSeq.getDatasetSequence() + Mapping map = new Mapping(ds, mapList); + DBRefEntry dbr = new DBRefEntry(getDbSource(), + getEnsemblDataVersion(), proteinSeq.getName(), map); + querySeq.getDatasetSequence().addDBRef(dbr); + List uprots = DBRefUtils.selectRefs(ds.getDBRefs(), + new String[] + { DBRefSource.UNIPROT }); + List upxrefs = DBRefUtils.selectRefs(querySeq.getDBRefs(), + new String[] + { DBRefSource.UNIPROT }); + if (uprots != null) { - AlignmentI seqal = new Alignment( - fr.getSeqsAsArray()); - for (SequenceI sq:seqal.getSequences()) + for (DBRefEntry up : uprots) { - if (ids.contains((sq.getName()))) + // locate local uniprot ref and map + List upx = DBRefUtils.searchRefs(upxrefs, + up.getAccessionId()); + DBRefEntry upxref; + if (upx.size() != 0) { - DBRefUtils.parseToDbRef(sq, "ENSEMBL", "0", sq.getName()); + upxref = upx.get(0); + + if (upx.size() > 1) + { + Cache.log.warn( + "Implementation issue - multiple uniprot acc on product sequence."); + } } - } - if (rtn == null) - { - rtn = seqal; - } - else - { - rtn.append(seqal); + else + { + upxref = new DBRefEntry(DBRefSource.UNIPROT, + getEnsemblDataVersion(), up.getAccessionId()); + } + + Mapping newMap = new Mapping(ds, mapList); + upxref.setVersion(getEnsemblDataVersion()); + upxref.setMap(newMap); + if (upx.size() == 0) + { + // add the new uniprot ref + querySeq.getDatasetSequence().addDBRef(upxref); + } + } } - } catch (Throwable r) + + /* + * copy exon features to protein, compute peptide variants from dna + * variants and add as features on the protein sequence ta-da + */ + AlignmentUtils.computeProteinFeatures(querySeq, proteinSeq, + mapList); + } + } catch (Exception e) + { + System.err + .println(String.format("Error retrieving protein for %s: %s", + accId, e.getMessage())); + } + } + + /** + * Get database xrefs from Ensembl, and attach them to the sequence + * + * @param seq + */ + protected void getCrossReferences(SequenceI seq) + { + + Platform.timeCheck("ESP. getdataseq ", Platform.TIME_MARK); + + + while (seq.getDatasetSequence() != null) + { + seq = seq.getDatasetSequence(); + } + + Platform.timeCheck("ESP. getxref ", Platform.TIME_MARK); + + EnsemblXref xrefFetcher = new EnsemblXref(getDomain(), getDbSource(), + getEnsemblDataVersion()); + List xrefs = xrefFetcher.getCrossReferences(seq.getName()); + + for (int i = 0, n = xrefs.size(); i < n; i++) + { +// Platform.timeCheck("ESP. getxref + " + (i) + "/" + n, Platform.TIME_MARK); + // BH 2019.01.25 this next method was taking 174 ms PER addition for a 266-reference example. + // DBRefUtils.ensurePrimaries(seq) + // was at the end of seq.addDBRef, so executed after ever addition! + // This method was moved to seq.getPrimaryDBRefs() + seq.addDBRef(xrefs.get(i)); + } + +// System.out.println("primaries are " + seq.getPrimaryDBRefs().toString()); + /* + * and add a reference to itself + */ + +// Platform.timeCheck("ESP. getxref self ", Platform.TIME_MARK); + + DBRefEntry self = new DBRefEntry(getDbSource(), getEnsemblDataVersion(), + seq.getName()); + +// Platform.timeCheck("ESP. getxref self add ", Platform.TIME_MARK); + + seq.addDBRef(self); + + Platform.timeCheck("ESP. seqprox done ", Platform.TIME_MARK); + + } + + /** + * Fetches sequences for the list of accession ids and adds them to the + * alignment. Returns the extended (or created) alignment. + * + * @param ids + * @param alignment + * @return + * @throws JalviewException + * @throws IOException + */ + protected AlignmentI fetchSequences(List ids, + AlignmentI alignment) throws JalviewException, IOException + { + if (!isEnsemblAvailable()) + { + inProgress = false; + throw new JalviewException("ENSEMBL Rest API not available."); + } + Platform.timeCheck("EnsemblSeqProx.fetchSeq ", Platform.TIME_MARK); + + List seqs = parseSequenceJson(ids); + if (seqs == null) + { + return alignment; + } + + if (seqs.isEmpty()) + { + throw new IOException("No data returned for " + ids); + } + + if (seqs.size() != ids.size()) + { + System.out.println(String.format( + "Only retrieved %d sequences for %d query strings", + seqs.size(), ids.size())); + } + + if (!seqs.isEmpty()) + { + AlignmentI seqal = new Alignment( + seqs.toArray(new SequenceI[seqs.size()])); + for (SequenceI seq : seqs) { - inProgress = false; - if (rtn != null) + if (seq.getDescription() == null) { - System.err.println("Aborting ID retrieval after " + v - + " chunks."); - r.printStackTrace(); + seq.setDescription(getDbName()); } - else + String name = seq.getName(); + if (ids.contains(name) + || ids.contains(name.replace("ENSP", "ENST"))) { - - throw new JalviewException("Aborting ID retrieval after " + v - + " chunks. Unexpected problem (" - + r.getLocalizedMessage() + ")", r); + // TODO JAL-3077 use true accession version in dbref + DBRefEntry dbref = DBRefUtils.parseToDbRef(seq, getDbSource(), + getEnsemblDataVersion(), name); + seq.addDBRef(dbref); } - + } + if (alignment == null) + { + alignment = seqal; + } + else + { + alignment.append(seqal); } } - inProgress = false; - return rtn; + return alignment; } /** + * Parses a JSON response for a single sequence ID query * - * @return the configured sequence return type for this source + * @param br + * @return a single jalview.datamodel.Sequence + * @see http://rest.ensembl.org/documentation/info/sequence_id */ - protected abstract EnsemblSeqType getSourceEnsemblType(); - - @Override - public boolean queryInProgress() + @SuppressWarnings("unchecked") + protected List parseSequenceJson(List ids) { - return inProgress; + List result = new ArrayList<>(); + try + { + /* + * for now, assumes only one sequence returned; refactor if needed + * in future to handle a JSONArray with more than one + */ + + Platform.timeCheck("ENS seqproxy", Platform.TIME_MARK); + Map val = (Map) getJSON(null, ids, -1, MODE_MAP, null); + if (val == null) + { + return null; + } + Object s = val.get("desc"); + String desc = s == null ? null : s.toString(); + s = val.get("id"); + String id = s == null ? null : s.toString(); + s = val.get("seq"); + String seq = s == null ? null : s.toString(); + Sequence sequence = new Sequence(id, seq); + if (desc != null) + { + sequence.setDescription(desc); + } + // todo JAL-3077 make a DBRefEntry with true accession version + // s = val.get("version"); + // String version = s == null ? "0" : s.toString(); + // DBRefEntry dbref = new DBRefEntry(getDbSource(), version, id); + // sequence.addDBRef(dbref); + result.add(sequence); + } catch (ParseException | IOException e) + { + System.err.println("Error processing JSON response: " + e.toString()); + // ignore + } + Platform.timeCheck("ENS seqproxy2", Platform.TIME_MARK); + return result; } + /** + * Returns the URL for the REST call + * + * @return + * @throws MalformedURLException + */ @Override - public StringBuffer getRawRecords() + protected URL getUrl(List ids) throws MalformedURLException { - return null; + /* + * a single id is included in the URL path + * multiple ids go in the POST body instead + */ + StringBuffer urlstring = new StringBuffer(128); + urlstring.append(getDomain() + "/sequence/id"); + 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=application/json")); + urlstring.append(("&content-type=application/json")); + + String objectType = getObjectType(); + if (objectType != null) + { + urlstring.append("&").append(OBJECT_TYPE).append("=") + .append(objectType); + } + + URL url = new URL(urlstring.toString()); + return url; } - @Override - public int getTier() + /** + * Override this method to specify object_type request parameter + * + * @return + */ + protected String getObjectType() { - return 0; + return null; } /** @@ -184,8 +578,417 @@ public abstract class EnsemblSeqProxy extends DbSourceProxyImpl } @Override - public boolean isDnaCoding() + protected boolean useGetRequest() + { + return false; + } + + /** + * + * @return the configured sequence return type for this source + */ + protected abstract EnsemblSeqType getSourceEnsemblType(); + + /** + * Returns a list of [start, end] genomic ranges corresponding to the sequence + * being retrieved. + * + * The correspondence between the frames of reference is made by locating + * those features on the genomic sequence which identify the retrieved + * sequence. Specifically + *
    + *
  • genomic sequence is identified by "transcript" features with + * ID=transcript:transcriptId
    • + *
  • cdna sequence is identified by "exon" features with + * Parent=transcript:transcriptId
    • + *
  • cds sequence is identified by "CDS" features with + * Parent=transcript:transcriptId
    • + *
+ * + * The returned ranges are sorted to run forwards (for positive strand) or + * backwards (for negative strand). Aborts and returns null if both positive + * and negative strand are found (this should not normally happen). + * + * @param sourceSequence + * @param accId + * @param start + * the start position of the sequence we are mapping to + * @return + */ + protected MapList getGenomicRangesFromFeatures(SequenceI sourceSequence, + String accId, int start) + { + List sfs = getIdentifyingFeatures(sourceSequence, + accId); + if (sfs.isEmpty()) + { + return null; + } + + /* + * generously initial size for number of cds regions + * (worst case titin Q8WZ42 has c. 313 exons) + */ + List regions = new ArrayList<>(100); + int mappedLength = 0; + int direction = 1; // forward + boolean directionSet = false; + + for (SequenceFeature sf : sfs) + { + 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; + } + direction = strand; + directionSet = true; + + /* + * add to CDS ranges, semi-sorted forwards/backwards + */ + if (strand < 0) + { + regions.add(0, new int[] { sf.getEnd(), sf.getBegin() }); + } + else + { + regions.add(new int[] { sf.getBegin(), sf.getEnd() }); + } + mappedLength += Math.abs(sf.getEnd() - sf.getBegin() + 1); + } + + 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, direction == 1 ? IntRangeComparator.ASCENDING + : IntRangeComparator.DESCENDING); + + List to = Arrays + .asList(new int[] + { start, start + mappedLength - 1 }); + + return new MapList(regions, to, 1, 1); + } + + /** + * Answers a list of sequence features that mark 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. For a gene sequence, this is trivially + * just the 'gene' feature with matching gene id. + * + * @param seq + * @param accId + * @return + */ + protected abstract List getIdentifyingFeatures( + SequenceI seq, String accId); + + int bhtest = 0; + + /** + * 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 mapping + * mapping from the sequence feature's coordinates to the target + * sequence + * @param forwardStrand + */ + protected void transferFeature(SequenceFeature sf, + SequenceI targetSequence, MapList mapping, boolean forwardStrand) + { + int start = sf.getBegin(); + int end = sf.getEnd(); + int[] mappedRange = mapping.locateInTo(start, end); + + if (mappedRange != null) + { +// Platform.timeCheck(null, Platform.TIME_SET); + String group = sf.getFeatureGroup(); + if (".".equals(group)) + { + group = getDbSource(); + } + int newBegin = Math.min(mappedRange[0], mappedRange[1]); + int newEnd = Math.max(mappedRange[0], mappedRange[1]); +// Platform.timeCheck(null, Platform.TIME_MARK); + bhtest++; + // 280 ms/1000 here: + SequenceFeature copy = new SequenceFeature(sf, newBegin, newEnd, group, sf.getScore()); + // 0.175 ms here: + targetSequence.addSequenceFeature(copy); + + /* + * for sequence_variant on reverse strand, have to convert the allele + * values to their complements + */ + if (!forwardStrand && SequenceOntologyFactory.getInstance() + .isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT)) + { + reverseComplementAlleles(copy); + } + } + } + + /** + * Change the 'alleles' value of a feature by converting to complementary + * bases, and also update the feature description to match + * + * @param sf + */ + static void reverseComplementAlleles(SequenceFeature sf) { + final String alleles = (String) sf.getValue(Gff3Helper.ALLELES); + if (alleles == null) + { + return; + } + StringBuilder complement = new StringBuilder(alleles.length()); + for (String allele : alleles.split(",")) + { + reverseComplementAllele(complement, allele); + } + String comp = complement.toString(); + sf.setValue(Gff3Helper.ALLELES, comp); + sf.setDescription(comp); + + /* + * replace value of "alleles=" in sf.ATTRIBUTES as well + * so 'output as GFF' shows reverse complement alleles + */ + String atts = sf.getAttributes(); + if (atts != null) + { + atts = atts.replace(Gff3Helper.ALLELES + "=" + alleles, + Gff3Helper.ALLELES + "=" + comp); + sf.setAttributes(atts); + } + } + + /** + * Makes the 'reverse complement' of the given allele and appends it to the + * buffer, after a comma separator if not the first + * + * @param complement + * @param allele + */ + static void reverseComplementAllele(StringBuilder complement, + String allele) + { + if (complement.length() > 0) + { + complement.append(","); + } + + /* + * some 'alleles' are actually descriptive terms + * e.g. HGMD_MUTATION, PhenCode_variation + * - we don't want to 'reverse complement' these + */ + if (!Comparison.isNucleotideSequence(allele, true)) + { + complement.append(allele); + } + else + { + for (int i = allele.length() - 1; i >= 0; i--) + { + complement.append(Dna.getComplement(allele.charAt(i))); + } + } + } + + /** + * Transfers features from sourceSequence to targetSequence + * + * @param accessionId + * @param sourceSequence + * @param targetSequence + * @return true if any features were transferred, else false + */ + protected boolean transferFeatures(String accessionId, + SequenceI sourceSequence, SequenceI targetSequence) + { + if (sourceSequence == null || targetSequence == null) + { + return false; + } + +// long start = System.currentTimeMillis(); + List sfs = sourceSequence.getFeatures() + .getPositionalFeatures(); + MapList mapping = getGenomicRangesFromFeatures(sourceSequence, + accessionId, targetSequence.getStart()); + if (mapping == null) + { + return false; + } + + + Platform.timeCheck("ESP. xfer " + sfs.size(), Platform.TIME_MARK); + + + boolean result = transferFeatures(sfs, targetSequence, mapping, + accessionId); +// System.out.println("transferFeatures (" + (sfs.size()) + " --> " +// + targetSequence.getFeatures().getFeatureCount(true) + ") 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 sfs + * @param targetSequence + * @param mapping + * @param parentId + * @return + */ + protected boolean transferFeatures(List sfs, + SequenceI targetSequence, MapList mapping, String parentId) + { + final boolean forwardStrand = mapping.isFromForwardStrand(); + + /* + * sort features by start position (which corresponds to end + * position descending if reverse strand) so as to add them in + * 'forwards' order to the target sequence + */ + SequenceFeatures.sortFeatures(sfs, forwardStrand); + + boolean transferred = false; + + for (int i = 0, n = sfs.size(); i < n; i++) + { + +// if ((i%1000) == 0) { +//// Platform.timeCheck("Feature " + bhtest, Platform.TIME_GET); +// Platform.timeCheck("ESP. xferFeature + " + (i) + "/" + n, Platform.TIME_MARK); +// } + + SequenceFeature sf = sfs.get(i); + if (retainFeature(sf, parentId)) + { + transferFeature(sf, targetSequence, mapping, forwardStrand); + transferred = true; + } + } + + return transferred; + } + + /** + * 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); + if (parent != null + && !parent.equalsIgnoreCase(identifier)) + { + // this genomic feature belongs to a different transcript + return false; + } return true; } + + /** + * Answers a short description of the sequence fetcher + */ + @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 term (or a sub-type of it), and the given + * identifier as parent + * + * @param sequence + * @param term + * @param parentId + * @return + */ + protected List findFeatures(SequenceI sequence, + String term, String parentId) + { + List result = new ArrayList<>(); + + List sfs = sequence.getFeatures() + .getFeaturesByOntology(term); + for (SequenceFeature sf : sfs) + { + String parent = (String) sf.getValue(PARENT); + if (parent != null && parent.equalsIgnoreCase(parentId)) + { + result.add(sf); + } + } + + 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 + * because NMD_transcript_variant behaves like 'transcript' in Ensembl + * although strictly speaking it is not (it is a sub-type of + * sequence_variant). + *

+ * (This test was needed when fetching transcript features as GFF. As we are + * now fetching as JSON, all features have type 'transcript' so the check for + * NMD_transcript_variant is redundant. Left in for any future case arising.) + * + * @param featureType + * @return + */ + public static boolean isTranscript(String featureType) + { + return SequenceOntologyI.NMD_TRANSCRIPT_VARIANT.equals(featureType) + || SequenceOntologyFactory.getInstance().isA(featureType, + SequenceOntologyI.TRANSCRIPT); + } }