X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fanalysis%2FAlignmentUtils.java;h=28f23b240812a81ddb989915d8c0ab54b097cc49;hb=cb8e52fbbc5f725e3f7f48c672cdddb0690bd978;hp=2b9b9f97c097afca3afffece8d8a1587e433a09d;hpb=be762d8d9c71a7aa3121e845c45911c7192b7827;p=jalview.git diff --git a/src/jalview/analysis/AlignmentUtils.java b/src/jalview/analysis/AlignmentUtils.java index 2b9b9f9..28f23b24 100644 --- a/src/jalview/analysis/AlignmentUtils.java +++ b/src/jalview/analysis/AlignmentUtils.java @@ -20,8 +20,26 @@ */ package jalview.analysis; -import static jalview.io.gff.GffConstants.CLINICAL_SIGNIFICANCE; +import java.util.Locale; +import java.util.ArrayList; +import java.util.Arrays; +import java.util.Collection; +import java.util.Collections; +import java.util.HashMap; +import java.util.HashSet; +import java.util.Iterator; +import java.util.LinkedHashMap; +import java.util.List; +import java.util.Map; +import java.util.Map.Entry; +import java.util.NoSuchElementException; +import java.util.Set; +import java.util.SortedMap; +import java.util.TreeMap; + +import jalview.bin.Console; +import jalview.commands.RemoveGapColCommand; import jalview.datamodel.AlignedCodon; import jalview.datamodel.AlignedCodonFrame; import jalview.datamodel.AlignedCodonFrame.SequenceToSequenceMapping; @@ -29,6 +47,7 @@ import jalview.datamodel.Alignment; import jalview.datamodel.AlignmentAnnotation; import jalview.datamodel.AlignmentI; import jalview.datamodel.DBRefEntry; +import jalview.datamodel.GeneLociI; import jalview.datamodel.IncompleteCodonException; import jalview.datamodel.Mapping; import jalview.datamodel.Sequence; @@ -43,25 +62,6 @@ import jalview.util.DBRefUtils; import jalview.util.IntRangeComparator; import jalview.util.MapList; import jalview.util.MappingUtils; -import jalview.util.StringUtils; - -import java.io.UnsupportedEncodingException; -import java.net.URLEncoder; -import java.util.ArrayList; -import java.util.Arrays; -import java.util.Collection; -import java.util.Collections; -import java.util.HashMap; -import java.util.HashSet; -import java.util.Iterator; -import java.util.LinkedHashMap; -import java.util.List; -import java.util.Map; -import java.util.Map.Entry; -import java.util.NoSuchElementException; -import java.util.Set; -import java.util.SortedMap; -import java.util.TreeMap; /** * grab bag of useful alignment manipulation operations Expect these to be @@ -72,12 +72,15 @@ import java.util.TreeMap; */ public class AlignmentUtils { - private static final int CODON_LENGTH = 3; private static final String SEQUENCE_VARIANT = "sequence_variant:"; - private static final String ID = "ID"; + /* + * the 'id' attribute is provided for variant features fetched from + * Ensembl using its REST service with JSON format + */ + public static final String VARIANT_ID = "id"; /** * A data model to hold the 'normal' base value at a position, and an optional @@ -105,6 +108,15 @@ public class AlignmentUtils { return variant == null ? null : variant.getFeatureGroup(); } + + /** + * toString for aid in the debugger only + */ + @Override + public String toString() + { + return base + ":" + (variant == null ? "" : variant.getDescription()); + } } /** @@ -117,7 +129,7 @@ public class AlignmentUtils */ public static AlignmentI expandContext(AlignmentI core, int flankSize) { - List sq = new ArrayList(); + List sq = new ArrayList<>(); int maxoffset = 0; for (SequenceI s : core.getSequences()) { @@ -172,9 +184,9 @@ public class AlignmentUtils // TODO use Character.toLowerCase to avoid creating String objects? char[] upstream = new String(ds .getSequence(s.getStart() - 1 - ustream_ds, s.getStart() - 1)) - .toLowerCase().toCharArray(); + .toLowerCase(Locale.ROOT).toCharArray(); char[] downstream = new String( - ds.getSequence(s_end - 1, s_end + dstream_ds)).toLowerCase() + ds.getSequence(s_end - 1, s_end + dstream_ds)).toLowerCase(Locale.ROOT) .toCharArray(); char[] coreseq = s.getSequence(); char[] nseq = new char[offset + upstream.length + downstream.length @@ -247,7 +259,7 @@ public class AlignmentUtils public static Map> getSequencesByName( AlignmentI al) { - Map> theMap = new LinkedHashMap>(); + Map> theMap = new LinkedHashMap<>(); for (SequenceI seq : al.getSequences()) { String name = seq.getName(); @@ -256,7 +268,7 @@ public class AlignmentUtils List seqs = theMap.get(name); if (seqs == null) { - seqs = new ArrayList(); + seqs = new ArrayList<>(); theMap.put(name, seqs); } seqs.add(seq); @@ -283,8 +295,8 @@ public class AlignmentUtils return false; } - Set mappedDna = new HashSet(); - Set mappedProtein = new HashSet(); + Set mappedDna = new HashSet<>(); + Set mappedProtein = new HashSet<>(); /* * First pass - map sequences where cross-references exist. This include @@ -384,7 +396,7 @@ public class AlignmentUtils * Answers true if the mappings include one between the given (dataset) * sequences. */ - public static boolean mappingExists(List mappings, + protected static boolean mappingExists(List mappings, SequenceI aaSeq, SequenceI cdnaSeq) { if (mappings != null) @@ -453,8 +465,8 @@ public class AlignmentUtils if (cdnaLength != mappedLength && cdnaLength > 2) { String lastCodon = String.valueOf(cdnaSeqChars, - cdnaLength - CODON_LENGTH, CODON_LENGTH).toUpperCase(); - for (String stop : ResidueProperties.STOP) + cdnaLength - CODON_LENGTH, CODON_LENGTH).toUpperCase(Locale.ROOT); + for (String stop : ResidueProperties.STOP_CODONS) { if (lastCodon.equals(stop)) { @@ -470,7 +482,7 @@ public class AlignmentUtils */ int startOffset = 0; if (cdnaLength != mappedLength && cdnaLength > 2 - && String.valueOf(cdnaSeqChars, 0, CODON_LENGTH).toUpperCase() + && String.valueOf(cdnaSeqChars, 0, CODON_LENGTH).toUpperCase(Locale.ROOT) .equals(ResidueProperties.START)) { startOffset += CODON_LENGTH; @@ -525,7 +537,8 @@ public class AlignmentUtils * allow * in protein to match untranslatable in dna */ final char aaRes = aaSeqChars[aaPos]; - if ((translated == null || "STOP".equals(translated)) && aaRes == '*') + if ((translated == null || ResidueProperties.STOP.equals(translated)) + && aaRes == '*') { continue; } @@ -557,7 +570,8 @@ public class AlignmentUtils if (dnaPos == cdnaSeqChars.length - CODON_LENGTH) { String codon = String.valueOf(cdnaSeqChars, dnaPos, CODON_LENGTH); - if ("STOP".equals(ResidueProperties.codonTranslate(codon))) + if (ResidueProperties.STOP + .equals(ResidueProperties.codonTranslate(codon))) { return true; } @@ -870,7 +884,7 @@ public class AlignmentUtils System.err.println("Wrong alignment type in alignProteinAsDna"); return 0; } - List unmappedProtein = new ArrayList(); + List unmappedProtein = new ArrayList<>(); Map> alignedCodons = buildCodonColumnsMap( protein, dna, unmappedProtein); return alignProteinAs(protein, alignedCodons, unmappedProtein); @@ -1081,7 +1095,7 @@ public class AlignmentUtils * {dnaSequence, {proteinSequence, codonProduct}} at that position. The * comparator keeps the codon positions ordered. */ - Map> alignedCodons = new TreeMap>( + Map> alignedCodons = new TreeMap<>( new CodonComparator()); for (SequenceI dnaSeq : dna.getSequences()) @@ -1127,9 +1141,9 @@ public class AlignmentUtils // TODO delete this ugly hack once JAL-2022 is resolved // i.e. we can model startPhase > 0 (incomplete start codon) - List sequencesChecked = new ArrayList(); + List sequencesChecked = new ArrayList<>(); AlignedCodon lastCodon = null; - Map toAdd = new HashMap(); + Map toAdd = new HashMap<>(); for (Entry> entry : alignedCodons .entrySet()) @@ -1308,7 +1322,7 @@ public class AlignmentUtils Map seqProduct = alignedCodons.get(codon); if (seqProduct == null) { - seqProduct = new HashMap(); + seqProduct = new HashMap<>(); alignedCodons.put(codon, seqProduct); } seqProduct.put(protein, codon); @@ -1445,7 +1459,7 @@ public class AlignmentUtils { continue; } - final List result = new ArrayList(); + final List result = new ArrayList<>(); for (AlignmentAnnotation dsann : datasetAnnotations) { /* @@ -1586,11 +1600,12 @@ public class AlignmentUtils return false; } String name = seq2.getName(); - final DBRefEntry[] xrefs = seq1.getDBRefs(); + final List xrefs = seq1.getDBRefs(); if (xrefs != null) { - for (DBRefEntry xref : xrefs) + for (int ix = 0, nx = xrefs.size(); ix < nx; ix++) { + DBRefEntry xref = xrefs.get(ix); String xrefName = xref.getSource() + "|" + xref.getAccessionId(); // case-insensitive test, consistent with DBRefEntry.equalRef() if (xrefName.equalsIgnoreCase(name)) @@ -1627,17 +1642,17 @@ public class AlignmentUtils throw new IllegalArgumentException( "IMPLEMENTATION ERROR: dataset.getDataset() must be null!"); } - List foundSeqs = new ArrayList(); - List cdsSeqs = new ArrayList(); + List foundSeqs = new ArrayList<>(); + List cdsSeqs = new ArrayList<>(); List mappings = dataset.getCodonFrames(); HashSet productSeqs = null; if (products != null) { - productSeqs = new HashSet(); + productSeqs = new HashSet<>(); for (SequenceI seq : products) { - productSeqs.add(seq.getDatasetSequence() == null ? seq - : seq.getDatasetSequence()); + productSeqs.add(seq.getDatasetSequence() == null ? seq : seq + .getDatasetSequence()); } } @@ -1720,32 +1735,36 @@ public class AlignmentUtils cdsSeqs.add(cdsSeq); - if (!dataset.getSequences().contains(cdsSeqDss)) - { - // check if this sequence is a newly created one - // so needs adding to the dataset - dataset.addSequence(cdsSeqDss); - } - /* - * add a mapping from CDS to the (unchanged) mapped to range + * build the mapping from CDS to protein */ List cdsRange = Collections .singletonList(new int[] - { 1, cdsSeq.getLength() }); + { cdsSeq.getStart(), + cdsSeq.getLength() + cdsSeq.getStart() - 1 }); MapList cdsToProteinMap = new MapList(cdsRange, mapList.getToRanges(), mapList.getFromRatio(), mapList.getToRatio()); - AlignedCodonFrame cdsToProteinMapping = new AlignedCodonFrame(); - cdsToProteinMapping.addMap(cdsSeqDss, proteinProduct, - cdsToProteinMap); - /* - * guard against duplicating the mapping if repeating this action - */ - if (!mappings.contains(cdsToProteinMapping)) + if (!dataset.getSequences().contains(cdsSeqDss)) { - mappings.add(cdsToProteinMapping); + /* + * if this sequence is a newly created one, add it to the dataset + * and made a CDS to protein mapping (if sequence already exists, + * CDS-to-protein mapping _is_ the transcript-to-protein mapping) + */ + dataset.addSequence(cdsSeqDss); + AlignedCodonFrame cdsToProteinMapping = new AlignedCodonFrame(); + cdsToProteinMapping.addMap(cdsSeqDss, proteinProduct, + cdsToProteinMap); + + /* + * guard against duplicating the mapping if repeating this action + */ + if (!mappings.contains(cdsToProteinMapping)) + { + mappings.add(cdsToProteinMapping); + } } propagateDBRefsToCDS(cdsSeqDss, dnaSeq.getDatasetSequence(), @@ -1754,7 +1773,7 @@ public class AlignmentUtils * add another mapping from original 'from' range to CDS */ AlignedCodonFrame dnaToCdsMapping = new AlignedCodonFrame(); - MapList dnaToCdsMap = new MapList(mapList.getFromRanges(), + final MapList dnaToCdsMap = new MapList(mapList.getFromRanges(), cdsRange, 1, 1); dnaToCdsMapping.addMap(dnaSeq.getDatasetSequence(), cdsSeqDss, dnaToCdsMap); @@ -1764,6 +1783,13 @@ public class AlignmentUtils } /* + * transfer dna chromosomal loci (if known) to the CDS + * sequence (via the mapping) + */ + final MapList cdsToDnaMap = dnaToCdsMap.getInverse(); + transferGeneLoci(dnaSeq, cdsToDnaMap, cdsSeq); + + /* * add DBRef with mapping from protein to CDS * (this enables Get Cross-References from protein alignment) * This is tricky because we can't have two DBRefs with the @@ -1780,31 +1806,35 @@ public class AlignmentUtils // need to // synthesize an xref. - for (DBRefEntry primRef : dnaDss.getPrimaryDBRefs()) + List primrefs = dnaDss.getPrimaryDBRefs(); + for (int ip = 0, np = primrefs.size(); ip < np; ip++) { - // creates a complementary cross-reference to the source sequence's - // primary reference. - - DBRefEntry cdsCrossRef = new DBRefEntry(primRef.getSource(), - primRef.getSource() + ":" + primRef.getVersion(), - primRef.getAccessionId()); - cdsCrossRef - .setMap(new Mapping(dnaDss, new MapList(dnaToCdsMap))); + DBRefEntry primRef = primrefs.get(ip); + /* + * create a cross-reference from CDS to the source sequence's + * primary reference and vice versa + */ + String source = primRef.getSource(); + String version = primRef.getVersion(); + DBRefEntry cdsCrossRef = new DBRefEntry(source, source + ":" + + version, primRef.getAccessionId()); + cdsCrossRef.setMap(new Mapping(dnaDss, new MapList(cdsToDnaMap))); cdsSeqDss.addDBRef(cdsCrossRef); + dnaSeq.addDBRef(new DBRefEntry(source, version, cdsSeq + .getName(), new Mapping(cdsSeqDss, dnaToCdsMap))); // problem here is that the cross-reference is synthesized - // cdsSeq.getName() may be like 'CDS|dnaaccession' or // 'CDS|emblcdsacc' // assuming cds version same as dna ?!? - DBRefEntry proteinToCdsRef = new DBRefEntry(primRef.getSource(), - primRef.getVersion(), cdsSeq.getName()); + DBRefEntry proteinToCdsRef = new DBRefEntry(source, version, + cdsSeq.getName()); // - proteinToCdsRef.setMap( - new Mapping(cdsSeqDss, cdsToProteinMap.getInverse())); + proteinToCdsRef.setMap(new Mapping(cdsSeqDss, cdsToProteinMap + .getInverse())); proteinProduct.addDBRef(proteinToCdsRef); } - /* * transfer any features on dna that overlap the CDS */ @@ -1814,14 +1844,46 @@ public class AlignmentUtils } } - AlignmentI cds = new Alignment( - cdsSeqs.toArray(new SequenceI[cdsSeqs.size()])); + AlignmentI cds = new Alignment(cdsSeqs.toArray(new SequenceI[cdsSeqs + .size()])); cds.setDataset(dataset); return cds; } /** + * Tries to transfer gene loci (dbref to chromosome positions) from fromSeq to + * toSeq, mediated by the given mapping between the sequences + * + * @param fromSeq + * @param targetToFrom + * Map + * @param targetSeq + */ + protected static void transferGeneLoci(SequenceI fromSeq, + MapList targetToFrom, SequenceI targetSeq) + { + if (targetSeq.getGeneLoci() != null) + { + // already have - don't override + return; + } + GeneLociI fromLoci = fromSeq.getGeneLoci(); + if (fromLoci == null) + { + return; + } + + MapList newMap = targetToFrom.traverse(fromLoci.getMapping()); + + if (newMap != null) + { + targetSeq.setGeneLoci(fromLoci.getSpeciesId(), + fromLoci.getAssemblyId(), fromLoci.getChromosomeId(), newMap); + } + } + + /** * A helper method that finds a CDS sequence in the alignment dataset that is * mapped to the given protein sequence, and either is, or has a mapping from, * the given dna sequence. @@ -1833,7 +1895,7 @@ public class AlignmentUtils * @param seqMappings * the set of mappings involving dnaSeq * @param aMapping - * an initial candidate from seqMappings + * a transcript-to-peptide mapping * @return */ static SequenceI findCdsForProtein(List mappings, @@ -1858,7 +1920,15 @@ public class AlignmentUtils if (mappedFromLength == dnaLength || mappedFromLength == dnaLength - CODON_LENGTH) { - return seqDss; + /* + * if sequence has CDS features, this is a transcript with no UTR + * - do not take this as the CDS sequence! (JAL-2789) + */ + if (seqDss.getFeatures().getFeaturesByOntology(SequenceOntologyI.CDS) + .isEmpty()) + { + return seqDss; + } } /* @@ -1883,10 +1953,12 @@ public class AlignmentUtils { /* * found a 3:1 mapping to the protein product which covers - * the whole dna sequence i.e. is from CDS; finally check it - * is from the dna start sequence + * the whole dna sequence i.e. is from CDS; finally check the CDS + * is mapped from the given dna start sequence */ SequenceI cdsSeq = map.getFromSeq(); + // todo this test is weak if seqMappings contains multiple mappings; + // we get away with it if transcript:cds relationship is 1:1 List dnaToCdsMaps = MappingUtils .findMappingsForSequence(cdsSeq, seqMappings); if (!dnaToCdsMaps.isEmpty()) @@ -1916,6 +1988,19 @@ public class AlignmentUtils static SequenceI makeCdsSequence(SequenceI seq, Mapping mapping, AlignmentI dataset) { + /* + * construct CDS sequence name as "CDS|" with 'from id' held in the mapping + * if set (e.g. EMBL protein_id), else sequence name appended + */ + String mapFromId = mapping.getMappedFromId(); + final String seqId = "CDS|" + + (mapFromId != null ? mapFromId : seq.getName()); + + SequenceI newSeq = null; + + /* + * construct CDS sequence by splicing mapped from ranges + */ char[] seqChars = seq.getSequence(); List fromRanges = mapping.getMap().getFromRanges(); int cdsWidth = MappingUtils.getLength(fromRanges); @@ -1940,15 +2025,10 @@ public class AlignmentUtils newSeqChars[newPos++] = Dna.getComplement(seqChars[i - 1]); } } + + newSeq = new Sequence(seqId, newSeqChars, 1, newPos); } - /* - * assign 'from id' held in the mapping if set (e.g. EMBL protein_id), - * else generate a sequence name - */ - String mapFromId = mapping.getMappedFromId(); - String seqId = "CDS|" + (mapFromId != null ? mapFromId : seq.getName()); - SequenceI newSeq = new Sequence(seqId, newSeqChars, 1, newPos); if (dataset != null) { SequenceI[] matches = dataset.findSequenceMatch(newSeq.getName()); @@ -1976,9 +2056,8 @@ public class AlignmentUtils } else { - System.err.println( - "JAL-2154 regression: warning - found (and ignnored a duplicate CDS sequence):" - + mtch.toString()); + Console.error( + "JAL-2154 regression: warning - found (and ignored) a duplicate CDS sequence:" + mtch.toString()); } } } @@ -1989,28 +2068,32 @@ public class AlignmentUtils } /** - * add any DBRefEntrys to cdsSeq from contig that have a Mapping congruent to + * Adds any DBRefEntrys to cdsSeq from contig that have a Mapping congruent to * the given mapping. * * @param cdsSeq * @param contig + * @param proteinProduct * @param mapping - * @return list of DBRefEntrys added. + * @return list of DBRefEntrys added */ - public static List propagateDBRefsToCDS(SequenceI cdsSeq, + protected static List propagateDBRefsToCDS(SequenceI cdsSeq, SequenceI contig, SequenceI proteinProduct, Mapping mapping) { - // gather direct refs from contig congrent with mapping - List direct = new ArrayList(); - HashSet directSources = new HashSet(); - if (contig.getDBRefs() != null) + // gather direct refs from contig congruent with mapping + List direct = new ArrayList<>(); + HashSet directSources = new HashSet<>(); + + List refs = contig.getDBRefs(); + if (refs != null) { - for (DBRefEntry dbr : contig.getDBRefs()) + for (int ib = 0, nb = refs.size(); ib < nb; ib++) { - if (dbr.hasMap() && dbr.getMap().getMap().isTripletMap()) + DBRefEntry dbr = refs.get(ib); + MapList map; + if (dbr.hasMap() && (map = dbr.getMap().getMap()).isTripletMap()) { - MapList map = dbr.getMap().getMap(); // check if map is the CDS mapping if (mapping.getMap().equals(map)) { @@ -2020,21 +2103,22 @@ public class AlignmentUtils } } } - DBRefEntry[] onSource = DBRefUtils.selectRefs( + List onSource = DBRefUtils.selectRefs( proteinProduct.getDBRefs(), directSources.toArray(new String[0])); - List propagated = new ArrayList(); + List propagated = new ArrayList<>(); // and generate appropriate mappings - for (DBRefEntry cdsref : direct) + for (int ic = 0, nc = direct.size(); ic < nc; ic++) { + DBRefEntry cdsref = direct.get(ic); + Mapping m = cdsref.getMap(); // clone maplist and mapping MapList cdsposmap = new MapList( Arrays.asList(new int[][] { new int[] { cdsSeq.getStart(), cdsSeq.getEnd() } }), - cdsref.getMap().getMap().getToRanges(), 3, 1); - Mapping cdsmap = new Mapping(cdsref.getMap().getTo(), - cdsref.getMap().getMap()); + m.getMap().getToRanges(), 3, 1); + Mapping cdsmap = new Mapping(m.getTo(), m.getMap()); // create dbref DBRefEntry newref = new DBRefEntry(cdsref.getSource(), @@ -2081,7 +2165,7 @@ public class AlignmentUtils * subtypes in the Sequence Ontology) * @param omitting */ - public static int transferFeatures(SequenceI fromSeq, SequenceI toSeq, + protected static int transferFeatures(SequenceI fromSeq, SequenceI toSeq, MapList mapping, String select, String... omitting) { SequenceI copyTo = toSeq; @@ -2089,6 +2173,10 @@ public class AlignmentUtils { copyTo = copyTo.getDatasetSequence(); } + if (fromSeq == copyTo || fromSeq.getDatasetSequence() == copyTo) + { + return 0; // shared dataset sequence + } /* * get features, optionally restricted by an ontology term @@ -2164,7 +2252,10 @@ public class AlignmentUtils /** * Returns a mapping from dna to protein by inspecting sequence features of - * type "CDS" on the dna. + * type "CDS" on the dna. A mapping is constructed if the total CDS feature + * length is 3 times the peptide length (optionally after dropping a trailing + * stop codon). This method does not check whether the CDS nucleotide sequence + * translates to the peptide sequence. * * @param dnaSeq * @param proteinSeq @@ -2176,6 +2267,16 @@ public class AlignmentUtils List ranges = findCdsPositions(dnaSeq); int mappedDnaLength = MappingUtils.getLength(ranges); + /* + * if not a whole number of codons, truncate mapping + */ + int codonRemainder = mappedDnaLength % CODON_LENGTH; + if (codonRemainder > 0) + { + mappedDnaLength -= codonRemainder; + MappingUtils.removeEndPositions(codonRemainder, ranges); + } + int proteinLength = proteinSeq.getLength(); int proteinStart = proteinSeq.getStart(); int proteinEnd = proteinSeq.getEnd(); @@ -2190,7 +2291,7 @@ public class AlignmentUtils proteinStart++; proteinLength--; } - List proteinRange = new ArrayList(); + List proteinRange = new ArrayList<>(); /* * dna length should map to protein (or protein plus stop codon) @@ -2199,8 +2300,12 @@ public class AlignmentUtils if (codesForResidues == (proteinLength + 1)) { // assuming extra codon is for STOP and not in peptide + // todo: check trailing codon is indeed a STOP codon codesForResidues--; + mappedDnaLength -= CODON_LENGTH; + MappingUtils.removeEndPositions(CODON_LENGTH, ranges); } + if (codesForResidues == proteinLength) { proteinRange.add(new int[] { proteinStart, proteinEnd }); @@ -2211,7 +2316,7 @@ public class AlignmentUtils /** * Returns a list of CDS ranges found (as sequence positions base 1), i.e. of - * start/end positions of sequence features of type "CDS" (or a sub-type of + * [start, end] positions of sequence features of type "CDS" (or a sub-type of * CDS in the Sequence Ontology). The ranges are sorted into ascending start * position order, so this method is only valid for linear CDS in the same * sense as the protein product. @@ -2219,9 +2324,9 @@ public class AlignmentUtils * @param dnaSeq * @return */ - public static List findCdsPositions(SequenceI dnaSeq) + protected static List findCdsPositions(SequenceI dnaSeq) { - List result = new ArrayList(); + List result = new ArrayList<>(); List sfs = dnaSeq.getFeatures().getFeaturesByOntology( SequenceOntologyI.CDS); @@ -2230,17 +2335,20 @@ public class AlignmentUtils return result; } SequenceFeatures.sortFeatures(sfs, true); - int startPhase = 0; for (SequenceFeature sf : sfs) { int phase = 0; try { - phase = Integer.parseInt(sf.getPhase()); + String s = sf.getPhase(); + if (s != null) + { + phase = Integer.parseInt(s); + } } catch (NumberFormatException e) { - // ignore + // leave as zero } /* * phase > 0 on first codon means 5' incomplete - skip to the start @@ -2248,7 +2356,7 @@ public class AlignmentUtils */ int begin = sf.getBegin(); int end = sf.getEnd(); - if (result.isEmpty()) + if (result.isEmpty() && phase > 0) { begin += phase; if (begin > end) @@ -2263,16 +2371,6 @@ public class AlignmentUtils } /* - * remove 'startPhase' positions (usually 0) from the first range - * so we begin at the start of a complete codon - */ - if (!result.isEmpty()) - { - // TODO JAL-2022 correctly model start phase > 0 - result.get(0)[0] += startPhase; - } - - /* * Finally sort ranges by start position. This avoids a dependency on * keeping features in order on the sequence (if they are in order anyway, * the sort will have almost no work to do). The implicit assumption is CDS @@ -2284,344 +2382,6 @@ public class AlignmentUtils } /** - * 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 - */ - public static int computeProteinFeatures(SequenceI dnaSeq, - SequenceI peptide, MapList dnaToProtein) - { - while (dnaSeq.getDatasetSequence() != null) - { - dnaSeq = dnaSeq.getDatasetSequence(); - } - while (peptide.getDatasetSequence() != null) - { - peptide = peptide.getDatasetSequence(); - } - - transferFeatures(dnaSeq, peptide, dnaToProtein, SequenceOntologyI.EXON); - - /* - * compute protein variants from dna variants and codon mappings; - * NB - alternatively we could retrieve this using the REST service e.g. - * http://rest.ensembl.org/overlap/translation - * /ENSP00000288602?feature=transcript_variation;content-type=text/xml - * which would be a bit slower but possibly more reliable - */ - - /* - * build a map with codon variations for each potentially varying peptide - */ - 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(); - List[] codonVariants = variant.getValue(); - count += computePeptideVariants(peptide, peptidePos, codonVariants); - } - - return count; - } - - /** - * Computes non-synonymous peptide variants from codon variants and adds them - * as sequence_variant features on the protein sequence (one feature per - * allele variant). Selected attributes (variant id, clinical significance) - * are copied over to the new features. - * - * @param peptide - * the protein sequence - * @param peptidePos - * the position to compute peptide variants for - * @param codonVariants - * a list of dna variants per codon position - * @return the number of features added - */ - static int computePeptideVariants(SequenceI peptide, int peptidePos, - List[] codonVariants) - { - String residue = String.valueOf(peptide.getCharAt(peptidePos - 1)); - int count = 0; - String base1 = codonVariants[0].get(0).base; - String base2 = codonVariants[1].get(0).base; - String base3 = codonVariants[2].get(0).base; - - /* - * variants in first codon base - */ - for (DnaVariant var : codonVariants[0]) - { - if (var.variant != null) - { - String alleles = (String) var.variant.getValue("alleles"); - if (alleles != null) - { - for (String base : alleles.split(",")) - { - String codon = base + base2 + base3; - if (addPeptideVariant(peptide, peptidePos, residue, var, codon)) - { - count++; - } - } - } - } - } - - /* - * variants in second codon base - */ - for (DnaVariant var : codonVariants[1]) - { - if (var.variant != null) - { - String alleles = (String) var.variant.getValue("alleles"); - if (alleles != null) - { - for (String base : alleles.split(",")) - { - String codon = base1 + base + base3; - if (addPeptideVariant(peptide, peptidePos, residue, var, codon)) - { - count++; - } - } - } - } - } - - /* - * variants in third codon base - */ - for (DnaVariant var : codonVariants[2]) - { - if (var.variant != null) - { - String alleles = (String) var.variant.getValue("alleles"); - if (alleles != null) - { - for (String base : alleles.split(",")) - { - String codon = base1 + base2 + base; - if (addPeptideVariant(peptide, peptidePos, residue, var, codon)) - { - count++; - } - } - } - } - } - - return count; - } - - /** - * Helper method that adds a peptide variant feature, provided the given codon - * translates to a value different to the current residue (is a non-synonymous - * variant). ID and clinical_significance attributes of the dna variant (if - * present) are copied to the new feature. - * - * @param peptide - * @param peptidePos - * @param residue - * @param var - * @param codon - * @return true if a feature was added, else false - */ - static boolean addPeptideVariant(SequenceI peptide, int peptidePos, - String residue, DnaVariant var, String codon) - { - /* - * get peptide translation of codon e.g. GAT -> D - * note that variants which are not single alleles, - * e.g. multibase variants or HGMD_MUTATION etc - * are currently ignored here - */ - String trans = codon.contains("-") ? "-" - : (codon.length() > CODON_LENGTH ? null - : ResidueProperties.codonTranslate(codon)); - if (trans != null && !trans.equals(residue)) - { - String residue3Char = StringUtils - .toSentenceCase(ResidueProperties.aa2Triplet.get(residue)); - String trans3Char = StringUtils - .toSentenceCase(ResidueProperties.aa2Triplet.get(trans)); - String desc = "p." + residue3Char + peptidePos + trans3Char; - SequenceFeature sf = new SequenceFeature( - SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos, - peptidePos, var.getSource()); - StringBuilder attributes = new StringBuilder(32); - String id = (String) var.variant.getValue(ID); - if (id != null) - { - if (id.startsWith(SEQUENCE_VARIANT)) - { - id = id.substring(SEQUENCE_VARIANT.length()); - } - sf.setValue(ID, id); - attributes.append(ID).append("=").append(id); - // TODO handle other species variants JAL-2064 - StringBuilder link = new StringBuilder(32); - try - { - link.append(desc).append(" ").append(id).append( - "|http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=") - .append(URLEncoder.encode(id, "UTF-8")); - sf.addLink(link.toString()); - } catch (UnsupportedEncodingException e) - { - // as if - } - } - String clinSig = (String) var.variant.getValue(CLINICAL_SIGNIFICANCE); - if (clinSig != null) - { - sf.setValue(CLINICAL_SIGNIFICANCE, clinSig); - attributes.append(";").append(CLINICAL_SIGNIFICANCE).append("=") - .append(clinSig); - } - peptide.addSequenceFeature(sf); - if (attributes.length() > 0) - { - sf.setAttributes(attributes.toString()); - } - return true; - } - return false; - } - - /** - * Builds a map whose key is position in the protein sequence, and value is a - * list of the base and all variants for each corresponding codon position - * - * @param dnaSeq - * @param dnaToProtein - * @return - */ - @SuppressWarnings("unchecked") - static LinkedHashMap[]> buildDnaVariantsMap( - SequenceI dnaSeq, MapList dnaToProtein) - { - /* - * map from peptide position to all variants of the codon which codes for it - * LinkedHashMap ensures we keep the peptide features in sequence order - */ - LinkedHashMap[]> variants = new LinkedHashMap[]>(); - - List dnaFeatures = dnaSeq.getFeatures() - .getFeaturesByOntology(SequenceOntologyI.SEQUENCE_VARIANT); - if (dnaFeatures.isEmpty()) - { - 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; - } - int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol); - if (mapsTo == null) - { - // feature doesn't lie within coding region - continue; - } - int peptidePosition = mapsTo[0]; - List[] codonVariants = variants.get(peptidePosition); - if (codonVariants == null) - { - codonVariants = new ArrayList[CODON_LENGTH]; - codonVariants[0] = new ArrayList(); - codonVariants[1] = new ArrayList(); - codonVariants[2] = new ArrayList(); - variants.put(peptidePosition, codonVariants); - } - - /* - * extract dna variants to a string array - */ - String alls = (String) sf.getValue("alleles"); - if (alls == null) - { - continue; - } - String[] alleles = alls.toUpperCase().split(","); - int i = 0; - for (String allele : alleles) - { - alleles[i++] = allele.trim(); // lose any space characters "A, G" - } - - /* - * get this peptide's 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 any variant) for each codon position - */ - for (int codonPos = 0; codonPos < CODON_LENGTH; codonPos++) - { - String nucleotide = String.valueOf( - dnaSeq.getCharAt(codon[codonPos] - dnaStart)).toUpperCase(); - List codonVariant = codonVariants[codonPos]; - if (codon[codonPos] == dnaCol) - { - if (!codonVariant.isEmpty() - && codonVariant.get(0).variant == null) - { - /* - * already recorded base value, add this variant - */ - codonVariant.get(0).variant = sf; - } - else - { - /* - * add variant with base value - */ - codonVariant.add(new DnaVariant(nucleotide, sf)); - } - } - else if (codonVariant.isEmpty()) - { - /* - * record (possibly non-varying) base value - */ - codonVariant.add(new DnaVariant(nucleotide)); - } - } - } - return variants; - } - - /** * Makes an alignment with a copy of the given sequences, adding in any * non-redundant sequences which are mapped to by the cross-referenced * sequences. @@ -2641,19 +2401,25 @@ public class AlignmentUtils SequenceIdMatcher matcher = new SequenceIdMatcher(seqs); if (xrefs != null) { - for (SequenceI xref : xrefs) + // BH 2019.01.25 recoded to remove iterators + + for (int ix = 0, nx = xrefs.length; ix < nx; ix++) { - DBRefEntry[] dbrefs = xref.getDBRefs(); + SequenceI xref = xrefs[ix]; + List dbrefs = xref.getDBRefs(); if (dbrefs != null) { - for (DBRefEntry dbref : dbrefs) + for (int ir = 0, nir = dbrefs.size(); ir < nir; ir++) { - if (dbref.getMap() == null || dbref.getMap().getTo() == null - || dbref.getMap().getTo().isProtein() != isProtein) + DBRefEntry dbref = dbrefs.get(ir); + Mapping map = dbref.getMap(); + SequenceI mto; + if (map == null || (mto = map.getTo()) == null + || mto.isProtein() != isProtein) { continue; } - SequenceI mappedTo = dbref.getMap().getTo(); + SequenceI mappedTo = mto; SequenceI match = matcher.findIdMatch(mappedTo); if (match == null) { @@ -2694,7 +2460,7 @@ public class AlignmentUtils /* * fancy case - aligning via mappings between sequences */ - List unmapped = new ArrayList(); + List unmapped = new ArrayList<>(); Map> columnMap = buildMappedColumnsMap( unaligned, aligned, unmapped); int width = columnMap.size(); @@ -2754,10 +2520,10 @@ public class AlignmentUtils * true; else returns false * * @param unaligned - * - sequences to be aligned based on aligned + * - sequences to be aligned based on aligned * @param aligned - * - 'guide' alignment containing sequences derived from same dataset - * as unaligned + * - 'guide' alignment containing sequences derived from same + * dataset as unaligned * @return */ static boolean alignAsSameSequences(AlignmentI unaligned, @@ -2769,7 +2535,7 @@ public class AlignmentUtils } // map from dataset sequence to alignment sequence(s) - Map> alignedDatasets = new HashMap>(); + Map> alignedDatasets = new HashMap<>(); for (SequenceI seq : aligned.getSequences()) { SequenceI ds = seq.getDatasetSequence(); @@ -2781,15 +2547,22 @@ public class AlignmentUtils } /* - * first pass - check whether all sequences to be aligned share a dataset - * sequence with an aligned sequence + * first pass - check whether all sequences to be aligned share a + * dataset sequence with an aligned sequence; also note the leftmost + * ungapped column from which to copy */ + int leftmost = Integer.MAX_VALUE; for (SequenceI seq : unaligned.getSequences()) { - if (!alignedDatasets.containsKey(seq.getDatasetSequence())) + final SequenceI ds = seq.getDatasetSequence(); + if (!alignedDatasets.containsKey(ds)) { return false; } + SequenceI alignedSeq = alignedDatasets.get(ds) + .get(0); + int startCol = alignedSeq.findIndex(seq.getStart()); // 1.. + leftmost = Math.min(leftmost, startCol); } /* @@ -2797,13 +2570,32 @@ public class AlignmentUtils * heuristic rule: pair off sequences in order for the case where * more than one shares the same dataset sequence */ + final char gapCharacter = aligned.getGapCharacter(); for (SequenceI seq : unaligned.getSequences()) { List alignedSequences = alignedDatasets .get(seq.getDatasetSequence()); - // TODO: getSequenceAsString() will be deprecated in the future - // TODO: need to leave to SequenceI implementor to update gaps - seq.setSequence(alignedSequences.get(0).getSequenceAsString()); + if (alignedSequences.isEmpty()) + { + /* + * defensive check - shouldn't happen! (JAL-3536) + */ + continue; + } + SequenceI alignedSeq = alignedSequences.get(0); + + /* + * gap fill for leading (5') UTR if any + */ + // TODO this copies intron columns - wrong! + int startCol = alignedSeq.findIndex(seq.getStart()); // 1.. + int endCol = alignedSeq.findIndex(seq.getEnd()); + char[] seqchars = new char[endCol - leftmost + 1]; + Arrays.fill(seqchars, gapCharacter); + char[] toCopy = alignedSeq.getSequence(startCol - 1, endCol); + System.arraycopy(toCopy, 0, seqchars, startCol - leftmost, + toCopy.length); + seq.setSequence(String.valueOf(seqchars)); if (alignedSequences.size() > 0) { // pop off aligned sequences (except the last one) @@ -2811,6 +2603,12 @@ public class AlignmentUtils } } + /* + * finally remove gapped columns (e.g. introns) + */ + new RemoveGapColCommand("", unaligned.getSequencesArray(), 0, + unaligned.getWidth() - 1, unaligned); + return true; } @@ -2832,7 +2630,7 @@ public class AlignmentUtils * {unalignedSequence, characterPerSequence} at that position. * TreeMap keeps the entries in ascending column order. */ - SortedMap> map = new TreeMap>(); + SortedMap> map = new TreeMap<>(); /* * record any sequences that have no mapping so can't be realigned @@ -2937,7 +2735,7 @@ public class AlignmentUtils Map seqsMap = map.get(fromCol); if (seqsMap == null) { - seqsMap = new HashMap(); + seqsMap = new HashMap<>(); map.put(fromCol, seqsMap); } seqsMap.put(seq, seq.getCharAt(mappedCharPos - toStart));