X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fext%2Fensembl%2FEnsemblSeqProxy.java;h=f96f1d5a4f36ad9c42349782b9031477365678c6;hb=f59dd9efbb3dfc313ab0b0507832e21cd0076fe1;hp=77263ffae3dcbda9f10445400b7faab3d362c128;hpb=e24933a537e0f640c75d4685c468615872bc77fc;p=jalview.git diff --git a/src/jalview/ext/ensembl/EnsemblSeqProxy.java b/src/jalview/ext/ensembl/EnsemblSeqProxy.java index 77263ff..f96f1d5 100644 --- a/src/jalview/ext/ensembl/EnsemblSeqProxy.java +++ b/src/jalview/ext/ensembl/EnsemblSeqProxy.java @@ -1,53 +1,71 @@ +/* + * 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.io.FastaFile; -import jalview.io.FileParse; +import jalview.io.gff.Gff3Helper; import jalview.io.gff.SequenceOntologyFactory; import jalview.io.gff.SequenceOntologyI; -import jalview.schemes.ResidueProperties; +import jalview.util.Comparison; import jalview.util.DBRefUtils; +import jalview.util.IntRangeComparator; import jalview.util.MapList; -import jalview.util.MappingUtils; -import jalview.util.StringUtils; +import java.io.BufferedReader; 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.Comparator; -import java.util.LinkedHashMap; import java.util.List; -import java.util.Map.Entry; + +import org.json.simple.JSONObject; +import org.json.simple.parser.JSONParser; +import org.json.simple.parser.ParseException; /** * Base class for Ensembl sequence fetchers * + * @see http://rest.ensembl.org/documentation/info/sequence_id * @author gmcarstairs */ public abstract class EnsemblSeqProxy extends EnsemblRestClient { - private static final List CROSS_REFERENCES = Arrays - .asList(new String[] { "CCDS", "Uniprot/SWISSPROT" }); - - protected static final String CONSEQUENCE_TYPE = "consequence_type"; - - protected static final String PARENT = "Parent"; - - protected static final String ID = "ID"; - protected static final String NAME = "Name"; + protected static final String DESCRIPTION = "description"; + /* * enum for 'type' parameter to the /sequence REST service */ @@ -59,7 +77,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient GENOMIC("genomic"), /** - * type=cdna to fetch dna including UTRs + * type=cdna to fetch coding dna including UTRs */ CDNA("cdna"), @@ -92,30 +110,19 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient } /** - * A comparator to sort ranges into ascending start position order + * Default constructor (to use rest.ensembl.org) */ - private class RangeSorter implements Comparator + public EnsemblSeqProxy() { - boolean forwards; - - RangeSorter(boolean forward) - { - forwards = forward; - } - - @Override - public int compare(int[] o1, int[] o2) - { - return (forwards ? 1 : -1) * Integer.compare(o1[0], o2[0]); - } - + super(); } /** - * Constructor + * Constructor given the target domain to fetch data from */ - public EnsemblSeqProxy() + public EnsemblSeqProxy(String d) { + super(d); } /** @@ -129,8 +136,8 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient // 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())); + List allIds = Arrays + .asList(query.split(getAccessionSeparator())); AlignmentI alignment = null; inProgress = true; @@ -153,6 +160,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient + " chunks. Unexpected problem (" + r.getLocalizedMessage() + ")"; System.err.println(msg); + r.printStackTrace(); break; } } @@ -198,14 +206,15 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient try { /* - * get 'dummy' genomic sequence with exon, cds and variation features + * get 'dummy' genomic sequence with gene, transcript, + * exon, cds and variation features */ SequenceI genomicSequence = null; - EnsemblFeatures gffFetcher = new EnsemblFeatures(); + EnsemblFeatures gffFetcher = new EnsemblFeatures(getDomain()); EnsemblFeatureType[] features = getFeaturesToFetch(); AlignmentI geneFeatures = gffFetcher.getSequenceRecords(accId, features); - if (geneFeatures.getHeight() > 0) + if (geneFeatures != null && geneFeatures.getHeight() > 0) { genomicSequence = geneFeatures.getSequenceAt(0); } @@ -214,7 +223,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient /* * transfer features to the query sequence */ - SequenceI querySeq = alignment.findName(accId); + SequenceI querySeq = alignment.findName(accId, true); if (transferFeatures(accId, genomicSequence, querySeq)) { @@ -227,8 +236,8 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient } } catch (IOException e) { - System.err.println("Error transferring Ensembl features: " - + e.getMessage()); + System.err.println( + "Error transferring Ensembl features: " + e.getMessage()); } } @@ -251,10 +260,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient String accId = querySeq.getName(); try { - AlignmentI protein = new EnsemblProtein().getSequenceRecords(accId); + AlignmentI protein = new EnsemblProtein(getDomain()) + .getSequenceRecords(accId); if (protein == null || protein.getHeight() == 0) { - System.out.println("Failed to retrieve protein for " + accId); + System.out.println("No protein product found for " + accId); return; } SequenceI proteinSeq = protein.getSequenceAt(0); @@ -265,22 +275,65 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient proteinSeq.createDatasetSequence(); querySeq.createDatasetSequence(); - MapList mapList = mapCdsToProtein(querySeq, proteinSeq); + 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(); - ds.setSourceDBRef(proteinSeq.getSourceDBRef()); + // TODO: Verify ensp primary ref is on proteinSeq.getDatasetSequence() Mapping map = new Mapping(ds, mapList); - DBRefEntry dbr = new DBRefEntry(getDbSource(), getDbVersion(), - accId, map); + DBRefEntry dbr = new DBRefEntry(getDbSource(), + getEnsemblDataVersion(), proteinSeq.getName(), map); querySeq.getDatasetSequence().addDBRef(dbr); - + DBRefEntry[] uprots = DBRefUtils.selectRefs(ds.getDBRefs(), + new String[] + { DBRefSource.UNIPROT }); + DBRefEntry[] upxrefs = DBRefUtils.selectRefs(querySeq.getDBRefs(), + new String[] + { DBRefSource.UNIPROT }); + if (uprots != null) + { + for (DBRefEntry up : uprots) + { + // locate local uniprot ref and map + List upx = DBRefUtils.searchRefs(upxrefs, + up.getAccessionId()); + DBRefEntry upxref; + if (upx.size() != 0) + { + upxref = upx.get(0); + + if (upx.size() > 1) + { + Cache.log.warn( + "Implementation issue - multiple uniprot acc on product sequence."); + } + } + 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); + } + + } + } + /* - * compute peptide variants from dna variants and add as - * sequence features on the protein sequence ta-da + * copy exon features to protein, compute peptide variants from dna + * variants and add as features on the protein sequence ta-da */ - computeProteinFeatures(querySeq, proteinSeq, mapList); + AlignmentUtils.computeProteinFeatures(querySeq, proteinSeq, + mapList); } } catch (Exception e) { @@ -302,131 +355,20 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient seq = seq.getDatasetSequence(); } - EnsemblXref xrefFetcher = new EnsemblXref(); - List xrefs = xrefFetcher.getCrossReferences(seq.getName(), - getCrossReferenceDatabases()); + EnsemblXref xrefFetcher = new EnsemblXref(getDomain(), getDbSource(), + getEnsemblDataVersion()); + List xrefs = xrefFetcher.getCrossReferences(seq.getName()); for (DBRefEntry xref : xrefs) { seq.addDBRef(xref); - /* - * Save any Uniprot xref to be the reference for SIFTS mapping - */ - if (DBRefSource.UNIPROT.equals(xref.getSource())) - { - seq.setSourceDBRef(xref); - } } - } - - /** - * Returns a list of database names to be used when fetching cross-references. - * - * @return - */ - protected List getCrossReferenceDatabases() - { - return CROSS_REFERENCES; - } - - /** - * Returns a mapping from dna to protein by inspecting sequence features of - * type "CDS" on the dna. - * - * @param dnaSeq - * @param proteinSeq - * @return - */ - protected MapList mapCdsToProtein(SequenceI dnaSeq, SequenceI proteinSeq) - { - List ranges = new ArrayList(50); - - int mappedDnaLength = getCdsRanges(dnaSeq, ranges); - - int proteinLength = proteinSeq.getLength(); - int proteinStart = 1; - - /* - * incomplete start codon may mean X at start of peptide - * we ignore both for mapping purposes - */ - if (proteinSeq.getCharAt(0) == 'X') - { - proteinStart = 2; - proteinLength--; - } - List proteinRange = new ArrayList(); /* - * dna length should map to protein (or protein plus stop codon) + * and add a reference to itself */ - int codesForResidues = mappedDnaLength / 3; - if (codesForResidues == (proteinLength + 1)) - { - MappingUtils.unmapStopCodon(ranges, mappedDnaLength); - codesForResidues--; - } - if (codesForResidues == proteinLength) - { - proteinRange.add(new int[] { proteinStart, proteinLength }); - return new MapList(ranges, proteinRange, 3, 1); - } - return null; - } - - /** - * Adds CDS ranges to the ranges list, and returns the total length mapped - * from. - * - * No need to worry about reverse strand dna, here since the retrieved - * sequence is as transcribed (reverse complement for reverse strand), i.e in - * the same sense as the peptide. - * - * @param dnaSeq - * @param ranges - * @return - */ - protected int getCdsRanges(SequenceI dnaSeq, List ranges) - { - SequenceFeature[] sfs = dnaSeq.getSequenceFeatures(); - if (sfs == null) - { - return 0; - } - SequenceOntologyI so = SequenceOntologyFactory.getInstance(); - int mappedDnaLength = 0; - for (SequenceFeature sf : sfs) - { - /* - * process a CDS feature (or a sub-type of CDS) - */ - if (so.isA(sf.getType(), SequenceOntologyI.CDS)) - { - int phase = 0; - try { - phase = Integer.parseInt(sf.getPhase()); - } catch (NumberFormatException e) - { - // ignore - } - /* - * phase > 0 on first codon means 5' incomplete - skip to the start - * of the next codon; example ENST00000496384 - */ - int begin = sf.getBegin(); - int end = sf.getEnd(); - if (ranges.isEmpty()) - { - begin += phase; - if (begin > end) - { - continue; // shouldn't happen? - } - } - ranges.add(new int[] { begin, end }); - mappedDnaLength += Math.abs(end - begin) + 1; - } - } - return mappedDnaLength; + DBRefEntry self = new DBRefEntry(getDbSource(), getEnsemblDataVersion(), + seq.getName()); + seq.addDBRef(self); } /** @@ -439,52 +381,52 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * @throws JalviewException * @throws IOException */ - protected AlignmentI fetchSequences(List ids, AlignmentI alignment) - throws JalviewException, IOException + protected AlignmentI fetchSequences(List ids, + AlignmentI alignment) throws JalviewException, IOException { if (!isEnsemblAvailable()) { inProgress = false; throw new JalviewException("ENSEMBL Rest API not available."); } - FileParse fp = getSequenceReader(ids); - FastaFile fr = new FastaFile(fp); - if (fr.hasWarningMessage()) + BufferedReader br = getSequenceReader(ids); + if (br == null) { - System.out.println(String.format( - "Warning when retrieving %d ids %s\n%s", ids.size(), - ids.toString(), fr.getWarningMessage())); + return alignment; } - else if (fr.getSeqs().size() != ids.size()) + + List seqs = parseSequenceJson(br); + + if (seqs.isEmpty()) { - System.out.println(String.format( - "Only retrieved %d sequences for %d query strings", fr - .getSeqs().size(), ids.size())); + throw new IOException("No data returned for " + ids); } - if (fr.getSeqs().size() == 1 && fr.getSeqs().get(0).getLength() == 0) + if (seqs.size() != ids.size()) { - /* - * POST request has returned an empty FASTA file e.g. for invalid id - */ - throw new IOException("No data returned for " + ids); + System.out.println(String.format( + "Only retrieved %d sequences for %d query strings", + seqs.size(), ids.size())); } - if (fr.getSeqs().size() > 0) + if (!seqs.isEmpty()) { AlignmentI seqal = new Alignment( - fr.getSeqsAsArray()); - for (SequenceI sq:seqal.getSequences()) + seqs.toArray(new SequenceI[seqs.size()])); + for (SequenceI seq : seqs) { - if (sq.getDescription() == null) + if (seq.getDescription() == null) { - sq.setDescription(getDbName()); + seq.setDescription(getDbName()); } - String name = sq.getName(); + String name = seq.getName(); if (ids.contains(name) || ids.contains(name.replace("ENSP", "ENST"))) { - DBRefUtils.parseToDbRef(sq, DBRefSource.ENSEMBL, "0", name); + // TODO JAL-3077 use true accession version in dbref + DBRefEntry dbref = DBRefUtils.parseToDbRef(seq, getDbSource(), + getEnsemblDataVersion(), name); + seq.addDBRef(dbref); } } if (alignment == null) @@ -500,6 +442,49 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient } /** + * Parses a JSON response into a list of sequences + * + * @param br + * @return + * @see http://rest.ensembl.org/documentation/info/sequence_id + */ + protected List parseSequenceJson(BufferedReader br) + { + JSONParser jp = new JSONParser(); + 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 + */ + final JSONObject val = (JSONObject) jp.parse(br); + 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 + } + return result; + } + + /** * Returns the URL for the REST call * * @return @@ -513,20 +498,38 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * multiple ids go in the POST body instead */ StringBuffer urlstring = new StringBuffer(128); - urlstring.append(SEQUENCE_ID_URL); + 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=text/x-fasta")); + 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 this method to specify object_type request parameter + * + * @return + */ + protected String getObjectType() + { + return null; + } + + /** * A sequence/id POST request currently allows up to 50 queries * * @see http://rest.ensembl.org/documentation/info/sequence_id_post @@ -543,18 +546,6 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient return false; } - @Override - protected String getRequestMimeType(boolean multipleIds) - { - return multipleIds ? "application/json" : "text/x-fasta"; - } - - @Override - protected String getResponseMimeType() - { - return "text/x-fasta"; - } - /** * * @return the configured sequence return type for this source @@ -590,8 +581,9 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient protected MapList getGenomicRangesFromFeatures(SequenceI sourceSequence, String accId, int start) { - SequenceFeature[] sfs = sourceSequence.getSequenceFeatures(); - if (sfs == null) + List sfs = sourceSequence.getFeatures() + .getPositionalFeatures(); + if (sfs.isEmpty()) { return null; } @@ -600,11 +592,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * generously initial size for number of cds regions * (worst case titin Q8WZ42 has c. 313 exons) */ - List regions = new ArrayList(100); + List regions = new ArrayList<>(100); int mappedLength = 0; int direction = 1; // forward boolean directionSet = false; - + for (SequenceFeature sf : sfs) { /* @@ -619,22 +611,22 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient 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 - { + 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); @@ -649,7 +641,7 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient } } } - + if (regions.isEmpty()) { System.out.println("Failed to identify target sequence for " + accId @@ -661,11 +653,13 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * a final sort is needed since Ensembl returns CDS sorted within source * (havana / ensembl_havana) */ - Collections.sort(regions, new RangeSorter(direction == 1)); - - List to = Arrays.asList(new int[] { start, - start + mappedLength - 1 }); - + 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); } @@ -692,6 +686,20 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient String accId); /** + * 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); + + /** * 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. @@ -701,36 +709,105 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * @param mapping * mapping from the sequence feature's coordinates to the target * sequence + * @param forwardStrand */ protected void transferFeature(SequenceFeature sf, - SequenceI targetSequence, MapList mapping) + SequenceI targetSequence, MapList mapping, boolean forwardStrand) { int start = sf.getBegin(); int end = sf.getEnd(); int[] mappedRange = mapping.locateInTo(start, end); - + if (mappedRange != null) { - SequenceFeature copy = new SequenceFeature(sf); - copy.setBegin(Math.min(mappedRange[0], mappedRange[1])); - copy.setEnd(Math.max(mappedRange[0], mappedRange[1])); + 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]); + SequenceFeature copy = new SequenceFeature(sf, newBegin, newEnd, + group, sf.getScore()); targetSequence.addSequenceFeature(copy); /* - * for sequence_variant, make an additional feature with consequence + * for sequence_variant on reverse strand, have to convert the allele + * values to their complements */ - // if (SequenceOntologyFactory.getInstance().isA(sf.getType(), - // SequenceOntologyI.SEQUENCE_VARIANT)) - // { - // String consequence = (String) sf.getValue(CONSEQUENCE_TYPE); - // if (consequence != null) - // { - // SequenceFeature sf2 = new SequenceFeature("consequence", - // consequence, copy.getBegin(), copy.getEnd(), 0f, - // null); - // targetSequence.addSequenceFeature(sf2); - // } - // } + 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))); + } } } @@ -750,10 +827,11 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient return false; } - // long start = System.currentTimeMillis(); - SequenceFeature[] sfs = sourceSequence.getSequenceFeatures(); - MapList mapping = getGenomicRangesFromFeatures(sourceSequence, accessionId, - targetSequence.getStart()); +// long start = System.currentTimeMillis(); + List sfs = sourceSequence.getFeatures() + .getPositionalFeatures(); + MapList mapping = getGenomicRangesFromFeatures(sourceSequence, + accessionId, targetSequence.getStart()); if (mapping == null) { return false; @@ -761,10 +839,10 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient boolean result = transferFeatures(sfs, targetSequence, mapping, accessionId); - // System.out.println("transferFeatures (" + (sfs.length) + " --> " - // + targetSequence.getSequenceFeatures().length + ") to " - // + targetSequence.getName() - // + " took " + (System.currentTimeMillis() - start) + "ms"); +// System.out.println("transferFeatures (" + (sfs.size()) + " --> " +// + targetSequence.getFeatures().getFeatureCount(true) + ") to " +// + targetSequence.getName() + " took " +// + (System.currentTimeMillis() - start) + "ms"); return result; } @@ -773,37 +851,30 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient * converted using the mapping. Features which do not overlap are ignored. * Features whose parent is not the specified identifier are also ignored. * - * @param features + * @param sfs * @param targetSequence * @param mapping * @param parentId * @return */ - protected boolean transferFeatures(SequenceFeature[] features, + protected boolean transferFeatures(List sfs, SequenceI targetSequence, MapList mapping, String parentId) { final boolean forwardStrand = mapping.isFromForwardStrand(); /* - * sort features by start position (descending if reverse strand) - * before transferring (in forwards order) to the target sequence + * 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 */ - Arrays.sort(features, new Comparator() - { - @Override - public int compare(SequenceFeature o1, SequenceFeature o2) - { - int c = Integer.compare(o1.getBegin(), o2.getBegin()); - return forwardStrand ? c : -c; - } - }); + SequenceFeatures.sortFeatures(sfs, forwardStrand); boolean transferred = false; - for (SequenceFeature sf : features) + for (SequenceFeature sf : sfs) { if (retainFeature(sf, parentId)) { - transferFeature(sf, targetSequence, mapping); + transferFeature(sf, targetSequence, mapping, forwardStrand); transferred = true; } } @@ -835,7 +906,8 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient { String parent = (String) sf.getValue(PARENT); // using contains to allow for prefix "gene:", "transcript:" etc - if (parent != null && !parent.contains(identifier)) + if (parent != null + && !parent.toUpperCase().contains(identifier.toUpperCase())) { // this genomic feature belongs to a different transcript return false; @@ -852,267 +924,30 @@ public abstract class EnsemblSeqProxy extends EnsemblRestClient /** * Returns a (possibly empty) list of features on the sequence which have the - * specified sequence ontology type (or a sub-type of it), and the given + * specified sequence ontology term (or a sub-type of it), and the given * identifier as parent * * @param sequence - * @param type + * @param term * @param parentId * @return */ protected List findFeatures(SequenceI sequence, - String type, String parentId) - { - List result = new ArrayList(); - - SequenceFeature[] sfs = sequence.getSequenceFeatures(); - if (sfs != null) { - SequenceOntologyI so = SequenceOntologyFactory.getInstance(); - for (SequenceFeature sf :sfs) { - if (so.isA(sf.getType(), type)) - { - String parent = (String) sf.getValue(PARENT); - if (parent.equals(parentId)) - { - result.add(sf); - } - } - } - } - return result; - } - - /** - * Maps exon features from dna to protein, and computes variants in peptide - * product generated by variants in dna, and adds them as sequence_variant - * features on the protein sequence. Returns the number of variant features - * added. - * - * @param dnaSeq - * @param peptide - * @param dnaToProtein - */ - static int computeProteinFeatures(SequenceI dnaSeq, - SequenceI peptide, MapList dnaToProtein) + String term, String parentId) { - while (dnaSeq.getDatasetSequence() != null) - { - dnaSeq = dnaSeq.getDatasetSequence(); - } - while (peptide.getDatasetSequence() != null) - { - peptide = peptide.getDatasetSequence(); - } - - AlignmentUtils.transferFeatures(dnaSeq, peptide, dnaToProtein, - SequenceOntologyI.EXON); + List result = new ArrayList<>(); - LinkedHashMap variants = buildDnaVariantsMap( - dnaSeq, dnaToProtein); - - /* - * scan codon variations, compute peptide variants and add to peptide sequence - */ - int count = 0; - for (Entry variant : variants.entrySet()) - { - int peptidePos = variant.getKey(); - String[][] codonVariants = variant.getValue(); - String residue = String.valueOf(peptide.getCharAt(peptidePos - 1)); // 0-based - List peptideVariants = computePeptideVariants(codonVariants, - residue); - if (!peptideVariants.isEmpty()) - { - String desc = StringUtils.listToDelimitedString(peptideVariants, - ", "); - SequenceFeature sf = new SequenceFeature( - SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos, - peptidePos, 0f, null); - peptide.addSequenceFeature(sf); - count++; - } - } - - /* - * ugly sort to get sequence features in start position order - * - would be better to store in Sequence as a TreeSet instead? - */ - Arrays.sort(peptide.getSequenceFeatures(), - new Comparator() - { - @Override - public int compare(SequenceFeature o1, SequenceFeature o2) - { - int c = Integer.compare(o1.getBegin(), o2.getBegin()); - return c == 0 ? Integer.compare(o1.getEnd(), o2.getEnd()) - : c; - } - }); - return count; - } - - /** - * Builds a map whose key is position in the protein sequence, and value is an - * array of all variants for the coding codon positions - * - * @param dnaSeq - * @param dnaToProtein - * @return - */ - static LinkedHashMap buildDnaVariantsMap( - SequenceI dnaSeq, MapList dnaToProtein) - { - /* - * map from peptide position to all variant features of the codon for it - * LinkedHashMap ensures we add the peptide features in sequence order - */ - LinkedHashMap variants = new LinkedHashMap(); - SequenceOntologyI so = SequenceOntologyFactory.getInstance(); - - SequenceFeature[] dnaFeatures = dnaSeq.getSequenceFeatures(); - if (dnaFeatures == null) - { - return variants; - } - - int dnaStart = dnaSeq.getStart(); - int[] lastCodon = null; - int lastPeptidePostion = 0; - - /* - * build a map of codon variations for peptides - */ - for (SequenceFeature sf : dnaFeatures) - { - int dnaCol = sf.getBegin(); - if (dnaCol != sf.getEnd()) - { - // not handling multi-locus variant features - continue; - } - if (so.isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT)) - { - int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol); - if (mapsTo == null) - { - // feature doesn't lie within coding region - continue; - } - int peptidePosition = mapsTo[0]; - String[][] codonVariants = variants.get(peptidePosition); - if (codonVariants == null) - { - codonVariants = new String[3][]; - variants.put(peptidePosition, codonVariants); - } - - /* - * extract dna variants to a string array - */ - String alls = (String) sf.getValue("alleles"); - if (alls == null) - { - continue; - } - String[] alleles = alls.split(","); - - /* - * get this peptides codon positions e.g. [3, 4, 5] or [4, 7, 10] - */ - int[] codon = peptidePosition == lastPeptidePostion ? lastCodon - : MappingUtils.flattenRanges(dnaToProtein.locateInFrom( - peptidePosition, peptidePosition)); - lastPeptidePostion = peptidePosition; - lastCodon = codon; - - /* - * save nucleotide (and this variant) for each codon position - */ - for (int codonPos = 0; codonPos < 3; codonPos++) - { - String nucleotide = String.valueOf(dnaSeq - .getCharAt(codon[codonPos] - dnaStart)); - if (codon[codonPos] == dnaCol) - { - /* - * record current dna base and its alleles - */ - String[] dnaVariants = new String[alleles.length + 1]; - dnaVariants[0] = nucleotide; - System.arraycopy(alleles, 0, dnaVariants, 1, alleles.length); - codonVariants[codonPos] = dnaVariants; - } - else if (codonVariants[codonPos] == null) - { - /* - * record current dna base only - * (at least until we find any variation and overwrite it) - */ - codonVariants[codonPos] = new String[] { nucleotide }; - } - } - } - } - return variants; - } - - /** - * Returns a sorted, non-redundant list of all peptide translations generated - * by the given dna variants, excluding the current residue value - * - * @param codonVariants - * an array of base values (acgtACGT) for codon positions 1, 2, 3 - * @param residue - * the current residue translation - * @return - */ - static List computePeptideVariants( - String[][] codonVariants, String residue) - { - List result = new ArrayList(); - for (String base1 : codonVariants[0]) + List sfs = sequence.getFeatures() + .getFeaturesByOntology(term); + for (SequenceFeature sf : sfs) { - for (String base2 : codonVariants[1]) + String parent = (String) sf.getValue(PARENT); + if (parent != null && parent.equalsIgnoreCase(parentId)) { - for (String base3 : codonVariants[2]) - { - String codon = base1 + base2 + base3; - // TODO: report frameshift/insertion/deletion - // and multiple-base variants?! - String peptide = codon.contains("-") ? "-" : ResidueProperties - .codonTranslate(codon); - if (peptide != null && !result.contains(peptide) - && !peptide.equalsIgnoreCase(residue)) - { - result.add(peptide); - } - } + result.add(sf); } } - /* - * sort alphabetically with STOP at the end - */ - Collections.sort(result, new Comparator() - { - - @Override - public int compare(String o1, String o2) - { - if ("STOP".equals(o1)) - { - return 1; - } - else if ("STOP".equals(o2)) - { - return -1; - } - else - { - return o1.compareTo(o2); - } - } - }); return result; }