X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fanalysis%2FAlignmentUtils.java;h=17aab155d78b2d468971df9f39389319b648d9d3;hb=d2b08d9048af25114cff8deabbd320471119d88d;hp=92753b97463c1ffced2f5f90a584f78c48dca2f4;hpb=13e9dc5c4c6b9b343c5bc2bcef49d54a296f03f5;p=jalview.git diff --git a/src/jalview/analysis/AlignmentUtils.java b/src/jalview/analysis/AlignmentUtils.java index 92753b9..17aab15 100644 --- a/src/jalview/analysis/AlignmentUtils.java +++ b/src/jalview/analysis/AlignmentUtils.java @@ -22,8 +22,10 @@ package jalview.analysis; import static jalview.io.gff.GffConstants.CLINICAL_SIGNIFICANCE; +import jalview.api.DBRefEntryI; import jalview.datamodel.AlignedCodon; import jalview.datamodel.AlignedCodonFrame; +import jalview.datamodel.AlignedCodonFrame.SequenceToSequenceMapping; import jalview.datamodel.Alignment; import jalview.datamodel.AlignmentAnnotation; import jalview.datamodel.AlignmentI; @@ -38,6 +40,7 @@ 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.MapList; import jalview.util.MappingUtils; import jalview.util.StringUtils; @@ -849,6 +852,11 @@ public class AlignmentUtils */ public static int alignProteinAsDna(AlignmentI protein, AlignmentI dna) { + if (protein.isNucleotide() || !dna.isNucleotide()) + { + System.err.println("Wrong alignment type in alignProteinAsDna"); + return 0; + } List unmappedProtein = new ArrayList(); Map> alignedCodons = buildCodonColumnsMap( protein, dna, unmappedProtein); @@ -856,6 +864,162 @@ public class AlignmentUtils } /** + * Realigns the given dna to match the alignment of the protein, using codon + * mappings to translate aligned peptide positions to codons. + * + * @param dna + * the alignment whose sequences are realigned by this method + * @param protein + * the protein alignment whose alignment we are 'copying' + * @return the number of sequences that were realigned + */ + public static int alignCdsAsProtein(AlignmentI dna, AlignmentI protein) + { + if (protein.isNucleotide() || !dna.isNucleotide()) + { + System.err.println("Wrong alignment type in alignProteinAsDna"); + return 0; + } + // todo: implement this + List mappings = protein.getCodonFrames(); + int alignedCount = 0; + for (SequenceI dnaSeq : dna.getSequences()) + { + if (alignCdsSequenceAsProtein(dnaSeq, protein, mappings, + dna.getGapCharacter())) + { + alignedCount++; + } + } + return alignedCount; + } + + /** + * Helper method to align (if possible) the dna sequence to match the + * alignment of a mapped protein sequence. This is currently limited to + * handling coding sequence only. + * + * @param cdsSeq + * @param protein + * @param mappings + * @param gapChar + * @return + */ + static boolean alignCdsSequenceAsProtein(SequenceI cdsSeq, + AlignmentI protein, List mappings, char gapChar) + { + SequenceI cdsDss = cdsSeq.getDatasetSequence(); + if (cdsDss == null) + { + System.err + .println("alignCdsSequenceAsProtein needs aligned sequence!"); + return false; + } + + List dnaMappings = MappingUtils + .findMappingsForSequence(cdsSeq, mappings); + for (AlignedCodonFrame mapping : dnaMappings) + { + SequenceI peptide = mapping.findAlignedSequence(cdsSeq, protein); + int peptideLength = peptide.getLength(); + if (peptide != null) + { + Mapping map = mapping.getMappingBetween(cdsSeq, peptide); + if (map != null) + { + MapList mapList = map.getMap(); + if (map.getTo() == peptide.getDatasetSequence()) + { + mapList = mapList.getInverse(); + } + int cdsLength = cdsDss.getLength(); + int mappedFromLength = MappingUtils.getLength(mapList + .getFromRanges()); + int mappedToLength = MappingUtils + .getLength(mapList.getToRanges()); + boolean addStopCodon = (cdsLength == mappedFromLength * 3 + 3) + || (peptide.getDatasetSequence().getLength() == mappedFromLength - 1); + if (cdsLength != mappedToLength && !addStopCodon) + { + System.err + .println(String + .format("Can't align cds as protein (length mismatch %d/%d): %s", + cdsLength, mappedToLength, + cdsSeq.getName())); + } + + /* + * pre-fill the aligned cds sequence with gaps + */ + char[] alignedCds = new char[peptideLength * 3 + + (addStopCodon ? 3 : 0)]; + Arrays.fill(alignedCds, gapChar); + + /* + * walk over the aligned peptide sequence and insert mapped + * codons for residues in the aligned cds sequence + */ + char[] alignedPeptide = peptide.getSequence(); + char[] nucleotides = cdsDss.getSequence(); + int copiedBases = 0; + int cdsStart = cdsDss.getStart(); + int proteinPos = peptide.getStart() - 1; + int cdsCol = 0; + for (char residue : alignedPeptide) + { + if (Comparison.isGap(residue)) + { + cdsCol += 3; + } + else + { + proteinPos++; + int[] codon = mapList.locateInTo(proteinPos, proteinPos); + if (codon == null) + { + // e.g. incomplete start codon, X in peptide + cdsCol += 3; + } + else + { + for (int j = codon[0]; j <= codon[1]; j++) + { + char mappedBase = nucleotides[j - cdsStart]; + alignedCds[cdsCol++] = mappedBase; + copiedBases++; + } + } + } + } + + /* + * append stop codon if not mapped from protein, + * closing it up to the end of the mapped sequence + */ + if (copiedBases == nucleotides.length - 3) + { + for (int i = alignedCds.length - 1; i >= 0; i--) + { + if (!Comparison.isGap(alignedCds[i])) + { + cdsCol = i + 1; // gap just after end of sequence + break; + } + } + for (int i = nucleotides.length - 3; i < nucleotides.length; i++) + { + alignedCds[cdsCol++] = nucleotides[i]; + } + } + cdsSeq.setSequence(new String(alignedCds)); + return true; + } + } + } + return false; + } + + /** * Builds a map whose key is an aligned codon position (3 alignment column * numbers base 0), and whose value is a map from protein sequence to each * protein's peptide residue for that codon. The map generates an ordering of @@ -1332,15 +1496,19 @@ public class AlignmentUtils Collection types, List forSequences, boolean anyType, boolean doShow) { - for (AlignmentAnnotation aa : al.getAlignmentAnnotation()) + AlignmentAnnotation[] anns = al.getAlignmentAnnotation(); + if (anns != null) { - if (anyType || types.contains(aa.label)) + for (AlignmentAnnotation aa : anns) { - if ((aa.sequenceRef != null) - && (forSequences == null || forSequences - .contains(aa.sequenceRef))) + if (anyType || types.contains(aa.label)) { - aa.visible = doShow; + if ((aa.sequenceRef != null) + && (forSequences == null || forSequences + .contains(aa.sequenceRef))) + { + aa.visible = doShow; + } } } } @@ -1399,75 +1567,272 @@ public class AlignmentUtils * added to the alignment dataset. * * @param dna - * aligned dna sequences - * @param mappings - * from dna to protein - * @param al + * aligned nucleotide (dna or cds) sequences + * @param dataset + * the alignment dataset the sequences belong to + * @param products + * (optional) to restrict results to CDS that map to specified + * protein products * @return an alignment whose sequences are the cds-only parts of the dna * sequences (or null if no mappings are found) */ public static AlignmentI makeCdsAlignment(SequenceI[] dna, - List mappings, AlignmentI al) + AlignmentI dataset, SequenceI[] products) { + if (dataset == null || dataset.getDataset() != null) + { + throw new IllegalArgumentException( + "IMPLEMENTATION ERROR: dataset.getDataset() must be null!"); + } + List foundSeqs = new ArrayList(); List cdsSeqs = new ArrayList(); - - for (SequenceI seq : dna) + List mappings = dataset.getCodonFrames(); + HashSet productSeqs = null; + if (products != null) { - AlignedCodonFrame cdsMappings = new AlignedCodonFrame(); + productSeqs = new HashSet(); + for (SequenceI seq : products) + { + productSeqs.add(seq.getDatasetSequence() == null ? seq : seq + .getDatasetSequence()); + } + } + + /* + * Construct CDS sequences from mappings on the alignment dataset. + * The logic is: + * - find the protein product(s) mapped to from each dna sequence + * - if the mapping covers the whole dna sequence (give or take start/stop + * codon), take the dna as the CDS sequence + * - else search dataset mappings for a suitable dna sequence, i.e. one + * whose whole sequence is mapped to the protein + * - if no sequence found, construct one from the dna sequence and mapping + * (and add it to dataset so it is found if this is repeated) + */ + for (SequenceI dnaSeq : dna) + { + SequenceI dnaDss = dnaSeq.getDatasetSequence() == null ? dnaSeq + : dnaSeq.getDatasetSequence(); + List seqMappings = MappingUtils - .findMappingsForSequence(seq, mappings); - List alignmentMappings = al.getCodonFrames(); + .findMappingsForSequence(dnaSeq, mappings); for (AlignedCodonFrame mapping : seqMappings) { - for (Mapping aMapping : mapping.getMappingsFromSequence(seq)) + List mappingsFromSequence = mapping + .getMappingsFromSequence(dnaSeq); + + for (Mapping aMapping : mappingsFromSequence) { - SequenceI cdsSeq = makeCdsSequence(seq.getDatasetSequence(), - aMapping); + MapList mapList = aMapping.getMap(); + if (mapList.getFromRatio() == 1) + { + /* + * not a dna-to-protein mapping (likely dna-to-cds) + */ + continue; + } + + /* + * skip if mapping is not to one of the target set of proteins + */ + SequenceI proteinProduct = aMapping.getTo(); + if (productSeqs != null && !productSeqs.contains(proteinProduct)) + { + continue; + } + + /* + * try to locate the CDS from the dataset mappings; + * guard against duplicate results (for the case that protein has + * dbrefs to both dna and cds sequences) + */ + SequenceI cdsSeq = findCdsForProtein(mappings, dnaSeq, + seqMappings, aMapping); + if (cdsSeq != null) + { + if (!foundSeqs.contains(cdsSeq)) + { + foundSeqs.add(cdsSeq); + SequenceI derivedSequence = cdsSeq.deriveSequence(); + cdsSeqs.add(derivedSequence); + if (!dataset.getSequences().contains(cdsSeq)) + { + dataset.addSequence(cdsSeq); + } + } + continue; + } + + /* + * didn't find mapped CDS sequence - construct it and add + * its dataset sequence to the dataset + */ + cdsSeq = makeCdsSequence(dnaSeq.getDatasetSequence(), aMapping); + SequenceI cdsSeqDss = cdsSeq.createDatasetSequence(); cdsSeqs.add(cdsSeq); - + if (!dataset.getSequences().contains(cdsSeqDss)) + { + dataset.addSequence(cdsSeqDss); + } + /* * add a mapping from CDS to the (unchanged) mapped to range */ List cdsRange = Collections.singletonList(new int[] { 1, cdsSeq.getLength() }); - MapList map = new MapList(cdsRange, aMapping.getMap() - .getToRanges(), aMapping.getMap().getFromRatio(), - aMapping.getMap().getToRatio()); - cdsMappings.addMap(cdsSeq, aMapping.getTo(), map); + MapList cdsToProteinMap = new MapList(cdsRange, mapList.getToRanges(), + mapList.getFromRatio(), mapList.getToRatio()); + AlignedCodonFrame cdsToProteinMapping = new AlignedCodonFrame(); + cdsToProteinMapping.addMap(cdsSeq, proteinProduct, cdsToProteinMap); + + /* + * guard against duplicating the mapping if repeating this action + */ + if (!mappings.contains(cdsToProteinMapping)) + { + mappings.add(cdsToProteinMapping); + } + + /* + * copy protein's dbrefs to CDS sequence + * this enables Get Cross-References from CDS alignment + */ + DBRefEntry[] proteinRefs = DBRefUtils.selectDbRefs(false, + proteinProduct.getDBRefs()); + if (proteinRefs != null) + { + for (DBRefEntry ref : proteinRefs) + { + DBRefEntry cdsToProteinRef = new DBRefEntry(ref); + cdsToProteinRef.setMap(new Mapping(proteinProduct, + cdsToProteinMap)); + cdsSeqDss.addDBRef(cdsToProteinRef); + } + } /* * add another mapping from original 'from' range to CDS */ - map = new MapList(aMapping.getMap().getFromRanges(), cdsRange, 1, + AlignedCodonFrame dnaToCdsMapping = new AlignedCodonFrame(); + MapList dnaToCdsMap = new MapList(mapList.getFromRanges(), + cdsRange, 1, 1); - cdsMappings.addMap(seq.getDatasetSequence(), cdsSeq, map); + dnaToCdsMapping.addMap(dnaSeq.getDatasetSequence(), cdsSeq, + dnaToCdsMap); + if (!mappings.contains(dnaToCdsMapping)) + { + mappings.add(dnaToCdsMapping); + } - alignmentMappings.add(cdsMappings); + /* + * 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 + * same source and accession, so need a different accession for + * the CDS from the dna sequence + */ + DBRefEntryI dnaRef = dnaDss.getSourceDBRef(); + if (dnaRef != null) + { + // assuming cds version same as dna ?!? + DBRefEntry proteinToCdsRef = new DBRefEntry(dnaRef.getSource(), + dnaRef.getVersion(), cdsSeq.getName()); + proteinToCdsRef.setMap(new Mapping(cdsSeqDss, cdsToProteinMap + .getInverse())); + proteinProduct.addDBRef(proteinToCdsRef); + } /* * transfer any features on dna that overlap the CDS */ - transferFeatures(seq, cdsSeq, map, null, SequenceOntologyI.CDS); + transferFeatures(dnaSeq, cdsSeq, cdsToProteinMap, null, + SequenceOntologyI.CDS); } } } + AlignmentI cds = new Alignment(cdsSeqs.toArray(new SequenceI[cdsSeqs + .size()])); + cds.setDataset(dataset); + + return cds; + } + + /** + * 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. + * + * @param mappings + * set of all mappings on the dataset + * @param dnaSeq + * a dna (or cds) sequence we are searching from + * @param seqMappings + * the set of mappings involving dnaSeq + * @param aMapping + * an initial candidate from seqMappings + * @return + */ + static SequenceI findCdsForProtein(List mappings, + SequenceI dnaSeq, List seqMappings, + Mapping aMapping) + { /* - * add CDS seqs to shared dataset + * TODO a better dna-cds-protein mapping data representation to allow easy + * navigation; until then this clunky looping around lists of mappings */ - Alignment dataset = al.getDataset(); - for (SequenceI seq : cdsSeqs) + SequenceI seqDss = dnaSeq.getDatasetSequence() == null ? dnaSeq + : dnaSeq.getDatasetSequence(); + SequenceI proteinProduct = aMapping.getTo(); + + /* + * is this mapping from the whole dna sequence (i.e. CDS)? + * allowing for possible stop codon on dna but not peptide + */ + int mappedFromLength = MappingUtils.getLength(aMapping.getMap() + .getFromRanges()); + int dnaLength = seqDss.getLength(); + if (mappedFromLength == dnaLength || mappedFromLength == dnaLength - 3) { - if (!dataset.getSequences().contains(seq.getDatasetSequence())) + return seqDss; + } + + /* + * looks like we found the dna-to-protein mapping; search for the + * corresponding cds-to-protein mapping + */ + List mappingsToPeptide = MappingUtils + .findMappingsForSequence(proteinProduct, mappings); + for (AlignedCodonFrame acf : mappingsToPeptide) + { + for (SequenceToSequenceMapping map : acf.getMappings()) { - dataset.addSequence(seq.getDatasetSequence()); + Mapping mapping = map.getMapping(); + if (mapping != aMapping && mapping.getMap().getFromRatio() == 3 + && proteinProduct == mapping.getTo() + && seqDss != map.getFromSeq()) + { + mappedFromLength = MappingUtils.getLength(mapping.getMap() + .getFromRanges()); + if (mappedFromLength == map.getFromSeq().getLength()) + { + /* + * 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 + */ + SequenceI cdsSeq = map.getFromSeq(); + List dnaToCdsMaps = MappingUtils + .findMappingsForSequence(cdsSeq, seqMappings); + if (!dnaToCdsMaps.isEmpty()) + { + return cdsSeq; + } + } + } } } - AlignmentI cds = new Alignment(cdsSeqs.toArray(new SequenceI[cdsSeqs - .size()])); - cds.setDataset(dataset); - - return cds; + return null; } /** @@ -1477,7 +1842,7 @@ public class AlignmentUtils * * @param seq * @param mapping - * @return + * @return CDS sequence (as a dataset sequence) */ static SequenceI makeCdsSequence(SequenceI seq, Mapping mapping) { @@ -1507,9 +1872,15 @@ public class AlignmentUtils } } - SequenceI newSeq = new Sequence(seq.getName() + "|" - + mapping.getTo().getName(), newSeqChars, 1, newPos); - newSeq.createDatasetSequence(); + /* + * 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); + // newSeq.setDescription(mapFromId); + return newSeq; } @@ -1795,17 +2166,20 @@ public class AlignmentUtils * sort to get sequence features in start position order * - would be better to store in Sequence as a TreeSet or NCList? */ - Arrays.sort(peptide.getSequenceFeatures(), - new Comparator() - { - @Override - public int compare(SequenceFeature o1, SequenceFeature o2) + if (peptide.getSequenceFeatures() != null) + { + Arrays.sort(peptide.getSequenceFeatures(), + new Comparator() { - int c = Integer.compare(o1.getBegin(), o2.getBegin()); - return c == 0 ? Integer.compare(o1.getEnd(), o2.getEnd()) - : c; - } - }); + @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; } @@ -1936,7 +2310,7 @@ public class AlignmentUtils // set score to 0f so 'graduated colour' option is offered! JAL-2060 SequenceFeature sf = new SequenceFeature( SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos, - peptidePos, 0f, null); + peptidePos, 0f, "Jalview"); StringBuilder attributes = new StringBuilder(32); String id = (String) var.variant.getValue(ID); if (id != null) @@ -2107,12 +2481,15 @@ public class AlignmentUtils * * @param seqs * @param xrefs + * @param dataset + * the alignment dataset shared by the new copy * @return */ public static AlignmentI makeCopyAlignment(SequenceI[] seqs, - SequenceI[] xrefs) + SequenceI[] xrefs, AlignmentI dataset) { AlignmentI copy = new Alignment(new Alignment(seqs)); + copy.setDataset(dataset); SequenceIdMatcher matcher = new SequenceIdMatcher(seqs); if (xrefs != null) @@ -2158,6 +2535,17 @@ public class AlignmentUtils */ public static int alignAs(AlignmentI unaligned, AlignmentI aligned) { + /* + * easy case - aligning a copy of aligned sequences + */ + if (alignAsSameSequences(unaligned, aligned)) + { + return unaligned.getHeight(); + } + + /* + * fancy case - aligning via mappings between sequences + */ List unmapped = new ArrayList(); Map> columnMap = buildMappedColumnsMap( unaligned, aligned, unmapped); @@ -2210,6 +2598,54 @@ public class AlignmentUtils } /** + * If unaligned and aligned sequences share the same dataset sequences, then + * simply copies the aligned sequences to the unaligned sequences and returns + * true; else returns false + * + * @param unaligned + * @param aligned + * @return + */ + static boolean alignAsSameSequences(AlignmentI unaligned, + AlignmentI aligned) + { + if (aligned.getDataset() == null || unaligned.getDataset() == null) + { + return false; // should only pass alignments with datasets here + } + + Map alignedDatasets = new HashMap(); + for (SequenceI seq : aligned.getSequences()) + { + alignedDatasets.put(seq.getDatasetSequence(), seq); + } + + /* + * first pass - check whether all sequences to be aligned share a dataset + * sequence with an aligned sequence + */ + for (SequenceI seq : unaligned.getSequences()) + { + if (!alignedDatasets.containsKey(seq.getDatasetSequence())) + { + return false; + } + } + + /* + * second pass - copy aligned sequences + */ + for (SequenceI seq : unaligned.getSequences()) + { + SequenceI alignedSequence = alignedDatasets.get(seq + .getDatasetSequence()); + seq.setSequence(alignedSequence.getSequenceAsString()); + } + + return true; + } + + /** * Returns a map whose key is alignment column number (base 1), and whose * values are a map of sequence characters in that column. * @@ -2223,13 +2659,13 @@ public class AlignmentUtils { /* * Map will hold, for each aligned column position, a map of - * {unalignedSequence, sequenceCharacter} at that position. + * {unalignedSequence, characterPerSequence} at that position. * TreeMap keeps the entries in ascending column order. */ Map> map = new TreeMap>(); /* - * r any sequences that have no mapping so can't be realigned + * record any sequences that have no mapping so can't be realigned */ unmapped.addAll(unaligned.getSequences()); @@ -2278,6 +2714,15 @@ public class AlignmentUtils return false; } + /* + * invert mapping if it is from unaligned to aligned sequence + */ + if (seqMap.getTo() == fromSeq.getDatasetSequence()) + { + seqMap = new Mapping(seq.getDatasetSequence(), seqMap.getMap() + .getInverse()); + } + char[] fromChars = fromSeq.getSequence(); int toStart = seq.getStart(); char[] toChars = seq.getSequence(); @@ -2311,7 +2756,8 @@ public class AlignmentUtils * of the next character of the mapped-to sequence; stop when all * the characters of the range have been counted */ - while (mappedCharPos <= range[1]) + while (mappedCharPos <= range[1] && fromCol <= fromChars.length + && fromCol >= 0) { if (!Comparison.isGap(fromChars[fromCol - 1])) {