X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;f=src%2Fjalview%2Fanalysis%2FAlignmentUtils.java;h=f2262fb7ef67c4c3da201fb95c285ccdcad44662;hb=c19d2a91ca05e052e3408bf5852d88eb5d0608f1;hp=6385fa75076c0ef2d32d715ae67781bcb8126f39;hpb=0b6b6af8bfba4edda36fef12a26c7526f4ee9555;p=jalview.git diff --git a/src/jalview/analysis/AlignmentUtils.java b/src/jalview/analysis/AlignmentUtils.java index 6385fa7..f2262fb 100644 --- a/src/jalview/analysis/AlignmentUtils.java +++ b/src/jalview/analysis/AlignmentUtils.java @@ -1,6 +1,6 @@ /* - * Jalview - A Sequence Alignment Editor and Viewer (Version 2.8.2) - * Copyright (C) 2014 The Jalview Authors + * Jalview - A Sequence Alignment Editor and Viewer (Version 2.9.0b2) + * Copyright (C) 2015 The Jalview Authors * * This file is part of Jalview. * @@ -20,12 +20,37 @@ */ package jalview.analysis; +import jalview.datamodel.AlignedCodon; +import jalview.datamodel.AlignedCodonFrame; +import jalview.datamodel.Alignment; import jalview.datamodel.AlignmentAnnotation; import jalview.datamodel.AlignmentI; +import jalview.datamodel.DBRefEntry; +import jalview.datamodel.DBRefSource; +import jalview.datamodel.FeatureProperties; +import jalview.datamodel.Mapping; +import jalview.datamodel.SearchResults; +import jalview.datamodel.Sequence; +import jalview.datamodel.SequenceGroup; import jalview.datamodel.SequenceI; +import jalview.schemes.ResidueProperties; +import jalview.util.DBRefUtils; +import jalview.util.MapList; +import jalview.util.MappingUtils; import java.util.ArrayList; +import java.util.Arrays; +import java.util.Collection; +import java.util.HashMap; +import java.util.HashSet; +import java.util.Iterator; +import java.util.LinkedHashMap; +import java.util.LinkedHashSet; import java.util.List; +import java.util.Map; +import java.util.Map.Entry; +import java.util.Set; +import java.util.TreeMap; /** * grab bag of useful alignment manipulation operations Expect these to be @@ -52,18 +77,22 @@ public class AlignmentUtils for (SequenceI s : core.getSequences()) { SequenceI newSeq = s.deriveSequence(); - if (newSeq.getStart() > maxoffset + final int newSeqStart = newSeq.getStart() - 1; + if (newSeqStart > maxoffset && newSeq.getDatasetSequence().getStart() < s.getStart()) { - maxoffset = newSeq.getStart(); + maxoffset = newSeqStart; } sq.add(newSeq); } if (flankSize > -1) { - maxoffset = flankSize; + maxoffset = Math.min(maxoffset, flankSize); } - // now add offset to create a new expanded alignment + + /* + * now add offset left and right to create an expanded alignment + */ for (SequenceI s : sq) { SequenceI ds = s; @@ -73,8 +102,8 @@ public class AlignmentUtils } int s_end = s.findPosition(s.getStart() + s.getLength()); // find available flanking residues for sequence - int ustream_ds = s.getStart() - ds.getStart(), dstream_ds = ds - .getEnd() - s_end; + int ustream_ds = s.getStart() - ds.getStart(); + int dstream_ds = ds.getEnd() - s_end; // build new flanked sequence @@ -90,27 +119,27 @@ public class AlignmentUtils offset = maxoffset - flankSize; ustream_ds = flankSize; } - if (flankSize < dstream_ds) + if (flankSize <= dstream_ds) { - dstream_ds = flankSize; + dstream_ds = flankSize - 1; } } + // 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(); - char[] downstream = new String(ds.getSequence(s_end - 1, s_end + 1 + char[] downstream = new String(ds.getSequence(s_end - 1, s_end + dstream_ds)).toLowerCase().toCharArray(); char[] coreseq = s.getSequence(); char[] nseq = new char[offset + upstream.length + downstream.length + coreseq.length]; char c = core.getGapCharacter(); - // TODO could lowercase the flanking regions + int p = 0; for (; p < offset; p++) { nseq[p] = c; } - // s.setSequence(new String(upstream).toLowerCase()+new String(coreseq) + - // new String(downstream).toLowerCase()); + System.arraycopy(upstream, 0, nseq, p, upstream.length); System.arraycopy(coreseq, 0, nseq, p + upstream.length, coreseq.length); @@ -128,6 +157,7 @@ public class AlignmentUtils { for (AlignmentAnnotation aa : s.getAnnotation()) { + aa.adjustForAlignment(); // JAL-1712 fix newAl.addAnnotation(aa); } } @@ -159,4 +189,1245 @@ public class AlignmentUtils } return result; } + + /** + * Returns a map of lists of sequences in the alignment, keyed by sequence + * name. For use in mapping between different alignment views of the same + * sequences. + * + * @see jalview.datamodel.AlignmentI#getSequencesByName() + */ + public static Map> getSequencesByName( + AlignmentI al) + { + Map> theMap = new LinkedHashMap>(); + for (SequenceI seq : al.getSequences()) + { + String name = seq.getName(); + if (name != null) + { + List seqs = theMap.get(name); + if (seqs == null) + { + seqs = new ArrayList(); + theMap.put(name, seqs); + } + seqs.add(seq); + } + } + return theMap; + } + + /** + * Build mapping of protein to cDNA alignment. Mappings are made between + * sequences where the cDNA translates to the protein sequence. Any new + * mappings are added to the protein alignment. Returns true if any mappings + * either already exist or were added, else false. + * + * @param proteinAlignment + * @param cdnaAlignment + * @return + */ + public static boolean mapProteinAlignmentToCdna( + final AlignmentI proteinAlignment, final AlignmentI cdnaAlignment) + { + if (proteinAlignment == null || cdnaAlignment == null) + { + return false; + } + + Set mappedDna = new HashSet(); + Set mappedProtein = new HashSet(); + + /* + * First pass - map sequences where cross-references exist. This include + * 1-to-many mappings to support, for example, variant cDNA. + */ + boolean mappingPerformed = mapProteinToCdna(proteinAlignment, + cdnaAlignment, mappedDna, mappedProtein, true); + + /* + * Second pass - map sequences where no cross-references exist. This only + * does 1-to-1 mappings and assumes corresponding sequences are in the same + * order in the alignments. + */ + mappingPerformed |= mapProteinToCdna(proteinAlignment, cdnaAlignment, + mappedDna, mappedProtein, false); + return mappingPerformed; + } + + /** + * Make mappings between compatible sequences (where the cDNA translation + * matches the protein). + * + * @param proteinAlignment + * @param cdnaAlignment + * @param mappedDna + * a set of mapped DNA sequences (to add to) + * @param mappedProtein + * a set of mapped Protein sequences (to add to) + * @param xrefsOnly + * if true, only map sequences where xrefs exist + * @return + */ + protected static boolean mapProteinToCdna( + final AlignmentI proteinAlignment, + final AlignmentI cdnaAlignment, Set mappedDna, + Set mappedProtein, boolean xrefsOnly) + { + boolean mappingExistsOrAdded = false; + List thisSeqs = proteinAlignment.getSequences(); + for (SequenceI aaSeq : thisSeqs) + { + boolean proteinMapped = false; + AlignedCodonFrame acf = new AlignedCodonFrame(); + + for (SequenceI cdnaSeq : cdnaAlignment.getSequences()) + { + /* + * Always try to map if sequences have xref to each other; this supports + * variant cDNA or alternative splicing for a protein sequence. + * + * If no xrefs, try to map progressively, assuming that alignments have + * mappable sequences in corresponding order. These are not + * many-to-many, as that would risk mixing species with similar cDNA + * sequences. + */ + if (xrefsOnly && !AlignmentUtils.haveCrossRef(aaSeq, cdnaSeq)) + { + continue; + } + + /* + * Don't map non-xrefd sequences more than once each. This heuristic + * allows us to pair up similar sequences in ordered alignments. + */ + if (!xrefsOnly + && (mappedProtein.contains(aaSeq) || mappedDna + .contains(cdnaSeq))) + { + continue; + } + if (mappingExists(proteinAlignment.getCodonFrames(), + aaSeq.getDatasetSequence(), cdnaSeq.getDatasetSequence())) + { + mappingExistsOrAdded = true; + } + else + { + MapList map = mapProteinSequenceToCdna(aaSeq, cdnaSeq); + if (map != null) + { + acf.addMap(cdnaSeq, aaSeq, map); + mappingExistsOrAdded = true; + proteinMapped = true; + mappedDna.add(cdnaSeq); + mappedProtein.add(aaSeq); + } + } + } + if (proteinMapped) + { + proteinAlignment.addCodonFrame(acf); + } + } + return mappingExistsOrAdded; + } + + /** + * Answers true if the mappings include one between the given (dataset) + * sequences. + */ + public static boolean mappingExists(Set set, + SequenceI aaSeq, SequenceI cdnaSeq) + { + if (set != null) + { + for (AlignedCodonFrame acf : set) + { + if (cdnaSeq == acf.getDnaForAaSeq(aaSeq)) + { + return true; + } + } + } + return false; + } + + /** + * Build a mapping (if possible) of a protein to a cDNA sequence. The cDNA + * must be three times the length of the protein, possibly after ignoring + * start and/or stop codons, and must translate to the protein. Returns null + * if no mapping is determined. + * + * @param proteinSeqs + * @param cdnaSeq + * @return + */ + public static MapList mapProteinSequenceToCdna(SequenceI proteinSeq, + SequenceI cdnaSeq) + { + /* + * Here we handle either dataset sequence set (desktop) or absent (applet). + * Use only the char[] form of the sequence to avoid creating possibly large + * String objects. + */ + final SequenceI proteinDataset = proteinSeq.getDatasetSequence(); + char[] aaSeqChars = proteinDataset != null ? proteinDataset + .getSequence() : proteinSeq.getSequence(); + final SequenceI cdnaDataset = cdnaSeq.getDatasetSequence(); + char[] cdnaSeqChars = cdnaDataset != null ? cdnaDataset.getSequence() + : cdnaSeq.getSequence(); + if (aaSeqChars == null || cdnaSeqChars == null) + { + return null; + } + + /* + * cdnaStart/End, proteinStartEnd are base 1 (for dataset sequence mapping) + */ + final int mappedLength = 3 * aaSeqChars.length; + int cdnaLength = cdnaSeqChars.length; + int cdnaStart = cdnaSeq.getStart(); + int cdnaEnd = cdnaSeq.getEnd(); + final int proteinStart = proteinSeq.getStart(); + final int proteinEnd = proteinSeq.getEnd(); + + /* + * If lengths don't match, try ignoring stop codon. + */ + if (cdnaLength != mappedLength && cdnaLength > 2) + { + String lastCodon = String.valueOf(cdnaSeqChars, cdnaLength - 3, 3) + .toUpperCase(); + for (String stop : ResidueProperties.STOP) + { + if (lastCodon.equals(stop)) + { + cdnaEnd -= 3; + cdnaLength -= 3; + break; + } + } + } + + /* + * If lengths still don't match, try ignoring start codon. + */ + int startOffset = 0; + if (cdnaLength != mappedLength + && cdnaLength > 2 + && String.valueOf(cdnaSeqChars, 0, 3).toUpperCase() + .equals(ResidueProperties.START)) + { + startOffset += 3; + cdnaStart += 3; + cdnaLength -= 3; + } + + if (cdnaLength != mappedLength) + { + return null; + } + if (!translatesAs(cdnaSeqChars, startOffset, aaSeqChars)) + { + return null; + } + MapList map = new MapList(new int[] { cdnaStart, cdnaEnd }, new int[] { + proteinStart, proteinEnd }, 3, 1); + return map; + } + + /** + * Test whether the given cdna sequence, starting at the given offset, + * translates to the given amino acid sequence, using the standard translation + * table. Designed to fail fast i.e. as soon as a mismatch position is found. + * + * @param cdnaSeqChars + * @param cdnaStart + * @param aaSeqChars + * @return + */ + protected static boolean translatesAs(char[] cdnaSeqChars, int cdnaStart, + char[] aaSeqChars) + { + if (cdnaSeqChars == null || aaSeqChars == null) + { + return false; + } + + int aaResidue = 0; + for (int i = cdnaStart; i < cdnaSeqChars.length - 2 + && aaResidue < aaSeqChars.length; i += 3, aaResidue++) + { + String codon = String.valueOf(cdnaSeqChars, i, 3); + final String translated = ResidueProperties.codonTranslate(codon); + /* + * allow * in protein to match untranslatable in dna + */ + final char aaRes = aaSeqChars[aaResidue]; + if ((translated == null || "STOP".equals(translated)) && aaRes == '*') + { + continue; + } + if (translated == null || !(aaRes == translated.charAt(0))) + { + // debug + // System.out.println(("Mismatch at " + i + "/" + aaResidue + ": " + // + codon + "(" + translated + ") != " + aaRes)); + return false; + } + } + // fail if we didn't match all of the aa sequence + return (aaResidue == aaSeqChars.length); + } + + /** + * Align sequence 'seq' to match the alignment of a mapped sequence. Note this + * currently assumes that we are aligning cDNA to match protein. + * + * @param seq + * the sequence to be realigned + * @param al + * the alignment whose sequence alignment is to be 'copied' + * @param gap + * character string represent a gap in the realigned sequence + * @param preserveUnmappedGaps + * @param preserveMappedGaps + * @return true if the sequence was realigned, false if it could not be + */ + public static boolean alignSequenceAs(SequenceI seq, AlignmentI al, + String gap, boolean preserveMappedGaps, + boolean preserveUnmappedGaps) + { + /* + * Get any mappings from the source alignment to the target (dataset) + * sequence. + */ + // TODO there may be one AlignedCodonFrame per dataset sequence, or one with + // all mappings. Would it help to constrain this? + List mappings = al.getCodonFrame(seq); + if (mappings == null || mappings.isEmpty()) + { + return false; + } + + /* + * Locate the aligned source sequence whose dataset sequence is mapped. We + * just take the first match here (as we can't align cDNA like more than one + * protein sequence). + */ + SequenceI alignFrom = null; + AlignedCodonFrame mapping = null; + for (AlignedCodonFrame mp : mappings) + { + alignFrom = mp.findAlignedSequence(seq.getDatasetSequence(), al); + if (alignFrom != null) + { + mapping = mp; + break; + } + } + + if (alignFrom == null) + { + return false; + } + alignSequenceAs(seq, alignFrom, mapping, gap, al.getGapCharacter(), + preserveMappedGaps, preserveUnmappedGaps); + return true; + } + + /** + * Align sequence 'alignTo' the same way as 'alignFrom', using the mapping to + * match residues and codons. Flags control whether existing gaps in unmapped + * (intron) and mapped (exon) regions are preserved or not. Gaps linking intro + * and exon are only retained if both flags are set. + * + * @param alignTo + * @param alignFrom + * @param mapping + * @param myGap + * @param sourceGap + * @param preserveUnmappedGaps + * @param preserveMappedGaps + */ + public static void alignSequenceAs(SequenceI alignTo, + SequenceI alignFrom, AlignedCodonFrame mapping, String myGap, + char sourceGap, boolean preserveMappedGaps, + boolean preserveUnmappedGaps) + { + // TODO generalise to work for Protein-Protein, dna-dna, dna-protein + final char[] thisSeq = alignTo.getSequence(); + final char[] thatAligned = alignFrom.getSequence(); + StringBuilder thisAligned = new StringBuilder(2 * thisSeq.length); + + // aligned and dataset sequence positions, all base zero + int thisSeqPos = 0; + int sourceDsPos = 0; + + int basesWritten = 0; + char myGapChar = myGap.charAt(0); + int ratio = myGap.length(); + + /* + * Traverse the aligned protein sequence. + */ + int fromOffset = alignFrom.getStart() - 1; + int toOffset = alignTo.getStart() - 1; + int sourceGapMappedLength = 0; + boolean inExon = false; + for (char sourceChar : thatAligned) + { + if (sourceChar == sourceGap) + { + sourceGapMappedLength += ratio; + continue; + } + + /* + * Found a residue. Locate its mapped codon (start) position. + */ + sourceDsPos++; + // Note mapping positions are base 1, our sequence positions base 0 + int[] mappedPos = mapping.getMappedRegion(alignTo, alignFrom, + sourceDsPos + fromOffset); + if (mappedPos == null) + { + /* + * Abort realignment if unmapped protein. Or could ignore it?? + */ + System.err.println("Can't align: no codon mapping to residue " + + sourceDsPos + "(" + sourceChar + ")"); + return; + } + + int mappedCodonStart = mappedPos[0]; // position (1...) of codon start + int mappedCodonEnd = mappedPos[mappedPos.length - 1]; // codon end pos + StringBuilder trailingCopiedGap = new StringBuilder(); + + /* + * Copy dna sequence up to and including this codon. Optionally, include + * gaps before the codon starts (in introns) and/or after the codon starts + * (in exons). + * + * Note this only works for 'linear' splicing, not reverse or interleaved. + * But then 'align dna as protein' doesn't make much sense otherwise. + */ + int intronLength = 0; + while (basesWritten + toOffset < mappedCodonEnd + && thisSeqPos < thisSeq.length) + { + final char c = thisSeq[thisSeqPos++]; + if (c != myGapChar) + { + basesWritten++; + int sourcePosition = basesWritten + toOffset; + if (sourcePosition < mappedCodonStart) + { + /* + * Found an unmapped (intron) base. First add in any preceding gaps + * (if wanted). + */ + if (preserveUnmappedGaps && trailingCopiedGap.length() > 0) + { + thisAligned.append(trailingCopiedGap.toString()); + intronLength += trailingCopiedGap.length(); + trailingCopiedGap = new StringBuilder(); + } + intronLength++; + inExon = false; + } + else + { + final boolean startOfCodon = sourcePosition == mappedCodonStart; + int gapsToAdd = calculateGapsToInsert(preserveMappedGaps, + preserveUnmappedGaps, sourceGapMappedLength, inExon, + trailingCopiedGap.length(), intronLength, startOfCodon); + for (int i = 0; i < gapsToAdd; i++) + { + thisAligned.append(myGapChar); + } + sourceGapMappedLength = 0; + inExon = true; + } + thisAligned.append(c); + trailingCopiedGap = new StringBuilder(); + } + else + { + if (inExon && preserveMappedGaps) + { + trailingCopiedGap.append(myGapChar); + } + else if (!inExon && preserveUnmappedGaps) + { + trailingCopiedGap.append(myGapChar); + } + } + } + } + + /* + * At end of protein sequence. Copy any remaining dna sequence, optionally + * including (intron) gaps. We do not copy trailing gaps in protein. + */ + while (thisSeqPos < thisSeq.length) + { + final char c = thisSeq[thisSeqPos++]; + if (c != myGapChar || preserveUnmappedGaps) + { + thisAligned.append(c); + } + } + + /* + * All done aligning, set the aligned sequence. + */ + alignTo.setSequence(new String(thisAligned)); + } + + /** + * Helper method to work out how many gaps to insert when realigning. + * + * @param preserveMappedGaps + * @param preserveUnmappedGaps + * @param sourceGapMappedLength + * @param inExon + * @param trailingCopiedGap + * @param intronLength + * @param startOfCodon + * @return + */ + protected static int calculateGapsToInsert(boolean preserveMappedGaps, + boolean preserveUnmappedGaps, int sourceGapMappedLength, + boolean inExon, int trailingGapLength, int intronLength, + final boolean startOfCodon) + { + int gapsToAdd = 0; + if (startOfCodon) + { + /* + * Reached start of codon. Ignore trailing gaps in intron unless we are + * preserving gaps in both exon and intron. Ignore them anyway if the + * protein alignment introduces a gap at least as large as the intronic + * region. + */ + if (inExon && !preserveMappedGaps) + { + trailingGapLength = 0; + } + if (!inExon && !(preserveMappedGaps && preserveUnmappedGaps)) + { + trailingGapLength = 0; + } + if (inExon) + { + gapsToAdd = Math.max(sourceGapMappedLength, trailingGapLength); + } + else + { + if (intronLength + trailingGapLength <= sourceGapMappedLength) + { + gapsToAdd = sourceGapMappedLength - intronLength; + } + else + { + gapsToAdd = Math.min(intronLength + trailingGapLength + - sourceGapMappedLength, trailingGapLength); + } + } + } + else + { + /* + * second or third base of codon; check for any gaps in dna + */ + if (!preserveMappedGaps) + { + trailingGapLength = 0; + } + gapsToAdd = Math.max(sourceGapMappedLength, trailingGapLength); + } + return gapsToAdd; + } + + /** + * Returns a list of sequences mapped from the given sequences and aligned + * (gapped) in the same way. For example, the cDNA for aligned protein, where + * a single gap in protein generates three gaps in cDNA. + * + * @param sequences + * @param gapCharacter + * @param mappings + * @return + */ + public static List getAlignedTranslation( + List sequences, char gapCharacter, + Set mappings) + { + List alignedSeqs = new ArrayList(); + + for (SequenceI seq : sequences) + { + List mapped = getAlignedTranslation(seq, gapCharacter, + mappings); + alignedSeqs.addAll(mapped); + } + return alignedSeqs; + } + + /** + * Returns sequences aligned 'like' the source sequence, as mapped by the + * given mappings. Normally we expect zero or one 'mapped' sequences, but this + * will support 1-to-many as well. + * + * @param seq + * @param gapCharacter + * @param mappings + * @return + */ + protected static List getAlignedTranslation(SequenceI seq, + char gapCharacter, Set mappings) + { + List result = new ArrayList(); + for (AlignedCodonFrame mapping : mappings) + { + if (mapping.involvesSequence(seq)) + { + SequenceI mapped = getAlignedTranslation(seq, gapCharacter, mapping); + if (mapped != null) + { + result.add(mapped); + } + } + } + return result; + } + + /** + * Returns the translation of 'seq' (as held in the mapping) with + * corresponding alignment (gaps). + * + * @param seq + * @param gapCharacter + * @param mapping + * @return + */ + protected static SequenceI getAlignedTranslation(SequenceI seq, + char gapCharacter, AlignedCodonFrame mapping) + { + String gap = String.valueOf(gapCharacter); + boolean toDna = false; + int fromRatio = 1; + SequenceI mapTo = mapping.getDnaForAaSeq(seq); + if (mapTo != null) + { + // mapping is from protein to nucleotide + toDna = true; + // should ideally get gap count ratio from mapping + gap = String.valueOf(new char[] { gapCharacter, gapCharacter, + gapCharacter }); + } + else + { + // mapping is from nucleotide to protein + mapTo = mapping.getAaForDnaSeq(seq); + fromRatio = 3; + } + StringBuilder newseq = new StringBuilder(seq.getLength() + * (toDna ? 3 : 1)); + + int residueNo = 0; // in seq, base 1 + int[] phrase = new int[fromRatio]; + int phraseOffset = 0; + int gapWidth = 0; + boolean first = true; + final Sequence alignedSeq = new Sequence("", ""); + + for (char c : seq.getSequence()) + { + if (c == gapCharacter) + { + gapWidth++; + if (gapWidth >= fromRatio) + { + newseq.append(gap); + gapWidth = 0; + } + } + else + { + phrase[phraseOffset++] = residueNo + 1; + if (phraseOffset == fromRatio) + { + /* + * Have read a whole codon (or protein residue), now translate: map + * source phrase to positions in target sequence add characters at + * these positions to newseq Note mapping positions are base 1, our + * sequence positions base 0. + */ + SearchResults sr = new SearchResults(); + for (int pos : phrase) + { + mapping.markMappedRegion(seq, pos, sr); + } + newseq.append(sr.getCharacters()); + if (first) + { + first = false; + // Hack: Copy sequence dataset, name and description from + // SearchResults.match[0].sequence + // TODO? carry over sequence names from original 'complement' + // alignment + SequenceI mappedTo = sr.getResultSequence(0); + alignedSeq.setName(mappedTo.getName()); + alignedSeq.setDescription(mappedTo.getDescription()); + alignedSeq.setDatasetSequence(mappedTo); + } + phraseOffset = 0; + } + residueNo++; + } + } + alignedSeq.setSequence(newseq.toString()); + return alignedSeq; + } + + /** + * Realigns the given protein to match the alignment of the dna, using codon + * mappings to translate aligned codon positions to protein residues. + * + * @param protein + * the alignment whose sequences are realigned by this method + * @param dna + * the dna alignment whose alignment we are 'copying' + * @return the number of sequences that were realigned + */ + public static int alignProteinAsDna(AlignmentI protein, AlignmentI dna) + { + List unmappedProtein = new ArrayList(); + unmappedProtein.addAll(protein.getSequences()); + + Set mappings = protein.getCodonFrames(); + + /* + * Map will hold, for each aligned codon position e.g. [3, 5, 6], a map of + * {dnaSequence, {proteinSequence, codonProduct}} at that position. The + * comparator keeps the codon positions ordered. + */ + Map> alignedCodons = new TreeMap>( + new CodonComparator()); + for (SequenceI dnaSeq : dna.getSequences()) + { + for (AlignedCodonFrame mapping : mappings) + { + Mapping seqMap = mapping.getMappingForSequence(dnaSeq); + SequenceI prot = mapping.findAlignedSequence( + dnaSeq.getDatasetSequence(), protein); + if (prot != null) + { + addCodonPositions(dnaSeq, prot, protein.getGapCharacter(), + seqMap, alignedCodons); + unmappedProtein.remove(prot); + } + } + } + return alignProteinAs(protein, alignedCodons, unmappedProtein); + } + + /** + * Update the aligned protein sequences to match the codon alignments given in + * the map. + * + * @param protein + * @param alignedCodons + * an ordered map of codon positions (columns), with sequence/peptide + * values present in each column + * @param unmappedProtein + * @return + */ + protected static int alignProteinAs(AlignmentI protein, + Map> alignedCodons, + List unmappedProtein) + { + /* + * Prefill aligned sequences with gaps before inserting aligned protein + * residues. + */ + int alignedWidth = alignedCodons.size(); + char[] gaps = new char[alignedWidth]; + Arrays.fill(gaps, protein.getGapCharacter()); + String allGaps = String.valueOf(gaps); + for (SequenceI seq : protein.getSequences()) + { + if (!unmappedProtein.contains(seq)) + { + seq.setSequence(allGaps); + } + } + + int column = 0; + for (AlignedCodon codon : alignedCodons.keySet()) + { + final Map columnResidues = alignedCodons + .get(codon); + for (Entry entry : columnResidues.entrySet()) + { + // place translated codon at its column position in sequence + entry.getKey().getSequence()[column] = entry.getValue().charAt(0); + } + column++; + } + return 0; + } + + /** + * Populate the map of aligned codons by traversing the given sequence + * mapping, locating the aligned positions of mapped codons, and adding those + * positions and their translation products to the map. + * + * @param dna + * the aligned sequence we are mapping from + * @param protein + * the sequence to be aligned to the codons + * @param gapChar + * the gap character in the dna sequence + * @param seqMap + * a mapping to a sequence translation + * @param alignedCodons + * the map we are building up + */ + static void addCodonPositions(SequenceI dna, SequenceI protein, + char gapChar, Mapping seqMap, + Map> alignedCodons) + { + Iterator codons = seqMap.getCodonIterator(dna, gapChar); + while (codons.hasNext()) + { + AlignedCodon codon = codons.next(); + Map seqProduct = alignedCodons.get(codon); + if (seqProduct == null) + { + seqProduct = new HashMap(); + alignedCodons.put(codon, seqProduct); + } + seqProduct.put(protein, codon.product); + } + } + + /** + * Returns true if a cDNA/Protein mapping either exists, or could be made, + * between at least one pair of sequences in the two alignments. Currently, + * the logic is: + *
    + *
  • One alignment must be nucleotide, and the other protein
    • + *
  • At least one pair of sequences must be already mapped, or mappable
    • + *
  • Mappable means the nucleotide translation matches the protein sequence
    • + *
  • The translation may ignore start and stop codons if present in the + * nucleotide
    • + *
+ * + * @param al1 + * @param al2 + * @return + */ + public static boolean isMappable(AlignmentI al1, AlignmentI al2) + { + if (al1 == null || al2 == null) + { + return false; + } + + /* + * Require one nucleotide and one protein + */ + if (al1.isNucleotide() == al2.isNucleotide()) + { + return false; + } + AlignmentI dna = al1.isNucleotide() ? al1 : al2; + AlignmentI protein = dna == al1 ? al2 : al1; + Set mappings = protein.getCodonFrames(); + for (SequenceI dnaSeq : dna.getSequences()) + { + for (SequenceI proteinSeq : protein.getSequences()) + { + if (isMappable(dnaSeq, proteinSeq, mappings)) + { + return true; + } + } + } + return false; + } + + /** + * Returns true if the dna sequence is mapped, or could be mapped, to the + * protein sequence. + * + * @param dnaSeq + * @param proteinSeq + * @param mappings + * @return + */ + protected static boolean isMappable(SequenceI dnaSeq, + SequenceI proteinSeq, Set mappings) + { + if (dnaSeq == null || proteinSeq == null) + { + return false; + } + + SequenceI dnaDs = dnaSeq.getDatasetSequence() == null ? dnaSeq : dnaSeq + .getDatasetSequence(); + SequenceI proteinDs = proteinSeq.getDatasetSequence() == null ? proteinSeq + : proteinSeq.getDatasetSequence(); + + /* + * Already mapped? + */ + for (AlignedCodonFrame mapping : mappings) + { + if (proteinDs == mapping.getAaForDnaSeq(dnaDs)) + { + return true; + } + } + + /* + * Just try to make a mapping (it is not yet stored), test whether + * successful. + */ + return mapProteinSequenceToCdna(proteinDs, dnaDs) != null; + } + + /** + * Finds any reference annotations associated with the sequences in + * sequenceScope, that are not already added to the alignment, and adds them + * to the 'candidates' map. Also populates a lookup table of annotation + * labels, keyed by calcId, for use in constructing tooltips or the like. + * + * @param sequenceScope + * the sequences to scan for reference annotations + * @param labelForCalcId + * (optional) map to populate with label for calcId + * @param candidates + * map to populate with annotations for sequence + * @param al + * the alignment to check for presence of annotations + */ + public static void findAddableReferenceAnnotations( + List sequenceScope, + Map labelForCalcId, + final Map> candidates, + AlignmentI al) + { + if (sequenceScope == null) + { + return; + } + + /* + * For each sequence in scope, make a list of any annotations on the + * underlying dataset sequence which are not already on the alignment. + * + * Add to a map of { alignmentSequence, } + */ + for (SequenceI seq : sequenceScope) + { + SequenceI dataset = seq.getDatasetSequence(); + if (dataset == null) + { + continue; + } + AlignmentAnnotation[] datasetAnnotations = dataset.getAnnotation(); + if (datasetAnnotations == null) + { + continue; + } + final List result = new ArrayList(); + for (AlignmentAnnotation dsann : datasetAnnotations) + { + /* + * Find matching annotations on the alignment. If none is found, then + * add this annotation to the list of 'addable' annotations for this + * sequence. + */ + final Iterable matchedAlignmentAnnotations = al + .findAnnotations(seq, dsann.getCalcId(), dsann.label); + if (!matchedAlignmentAnnotations.iterator().hasNext()) + { + result.add(dsann); + if (labelForCalcId != null) + { + labelForCalcId.put(dsann.getCalcId(), dsann.label); + } + } + } + /* + * Save any addable annotations for this sequence + */ + if (!result.isEmpty()) + { + candidates.put(seq, result); + } + } + } + + /** + * Adds annotations to the top of the alignment annotations, in the same order + * as their related sequences. + * + * @param annotations + * the annotations to add + * @param alignment + * the alignment to add them to + * @param selectionGroup + * current selection group (or null if none) + */ + public static void addReferenceAnnotations( + Map> annotations, + final AlignmentI alignment, final SequenceGroup selectionGroup) + { + for (SequenceI seq : annotations.keySet()) + { + for (AlignmentAnnotation ann : annotations.get(seq)) + { + AlignmentAnnotation copyAnn = new AlignmentAnnotation(ann); + int startRes = 0; + int endRes = ann.annotations.length; + if (selectionGroup != null) + { + startRes = selectionGroup.getStartRes(); + endRes = selectionGroup.getEndRes(); + } + copyAnn.restrict(startRes, endRes); + + /* + * Add to the sequence (sets copyAnn.datasetSequence), unless the + * original annotation is already on the sequence. + */ + if (!seq.hasAnnotation(ann)) + { + seq.addAlignmentAnnotation(copyAnn); + } + // adjust for gaps + copyAnn.adjustForAlignment(); + // add to the alignment and set visible + alignment.addAnnotation(copyAnn); + copyAnn.visible = true; + } + } + } + + /** + * Set visibility of alignment annotations of specified types (labels), for + * specified sequences. This supports controls like + * "Show all secondary structure", "Hide all Temp factor", etc. + * + * @al the alignment to scan for annotations + * @param types + * the types (labels) of annotations to be updated + * @param forSequences + * if not null, only annotations linked to one of these sequences are + * in scope for update; if null, acts on all sequence annotations + * @param anyType + * if this flag is true, 'types' is ignored (label not checked) + * @param doShow + * if true, set visibility on, else set off + */ + public static void showOrHideSequenceAnnotations(AlignmentI al, + Collection types, List forSequences, + boolean anyType, boolean doShow) + { + for (AlignmentAnnotation aa : al.getAlignmentAnnotation()) + { + if (anyType || types.contains(aa.label)) + { + if ((aa.sequenceRef != null) + && (forSequences == null || forSequences + .contains(aa.sequenceRef))) + { + aa.visible = doShow; + } + } + } + } + + /** + * Returns true if either sequence has a cross-reference to the other + * + * @param seq1 + * @param seq2 + * @return + */ + public static boolean haveCrossRef(SequenceI seq1, SequenceI seq2) + { + // Note: moved here from class CrossRef as the latter class has dependencies + // not availability to the applet's classpath + return hasCrossRef(seq1, seq2) || hasCrossRef(seq2, seq1); + } + + /** + * Returns true if seq1 has a cross-reference to seq2. Currently this assumes + * that sequence name is structured as Source|AccessionId. + * + * @param seq1 + * @param seq2 + * @return + */ + public static boolean hasCrossRef(SequenceI seq1, SequenceI seq2) + { + if (seq1 == null || seq2 == null) + { + return false; + } + String name = seq2.getName(); + final DBRefEntry[] xrefs = seq1.getDBRef(); + if (xrefs != null) + { + for (DBRefEntry xref : xrefs) + { + String xrefName = xref.getSource() + "|" + xref.getAccessionId(); + // case-insensitive test, consistent with DBRefEntry.equalRef() + if (xrefName.equalsIgnoreCase(name)) + { + return true; + } + } + } + return false; + } + + /** + * Constructs an alignment consisting of the mapped exon regions in the given + * nucleotide sequences, and updates mappings to match. + * + * @param dna + * aligned dna sequences + * @param mappings + * from dna to protein; these are replaced with new mappings + * @return an alignment whose sequences are the exon-only parts of the dna + * sequences (or null if no exons are found) + */ + public static AlignmentI makeExonAlignment(SequenceI[] dna, + Set mappings) + { + Set newMappings = new LinkedHashSet(); + List exonSequences = new ArrayList(); + + for (SequenceI dnaSeq : dna) + { + final SequenceI ds = dnaSeq.getDatasetSequence(); + List seqMappings = MappingUtils + .findMappingsForSequence(ds, mappings); + for (AlignedCodonFrame acf : seqMappings) + { + AlignedCodonFrame newMapping = new AlignedCodonFrame(); + final List mappedExons = makeExonSequences(ds, acf, + newMapping); + if (!mappedExons.isEmpty()) + { + exonSequences.addAll(mappedExons); + newMappings.add(newMapping); + } + } + } + AlignmentI al = new Alignment( + exonSequences.toArray(new SequenceI[exonSequences.size()])); + al.setDataset(null); + + /* + * Replace the old mappings with the new ones + */ + mappings.clear(); + mappings.addAll(newMappings); + + return al; + } + + /** + * Helper method to make exon-only sequences and populate their mappings to + * protein products + *

+ * For example, if ggCCaTTcGAg has mappings [3, 4, 6, 7, 9, 10] to protein + * then generate a sequence CCTTGA with mapping [1, 6] to the same protein + * residues + *

+ * Typically eukaryotic dna will include exons encoding for a single peptide + * sequence i.e. return a single result. Bacterial dna may have overlapping + * exon mappings coding for multiple peptides so return multiple results + * (example EMBL KF591215). + * + * @param dnaSeq + * a dna dataset sequence + * @param mapping + * containing one or more mappings of the sequence to protein + * @param newMapping + * the new mapping to populate, from the exon-only sequences to their + * mapped protein sequences + * @return + */ + protected static List makeExonSequences(SequenceI dnaSeq, + AlignedCodonFrame mapping, AlignedCodonFrame newMapping) + { + List exonSequences = new ArrayList(); + List seqMappings = mapping.getMappingsForSequence(dnaSeq); + final char[] dna = dnaSeq.getSequence(); + for (Mapping seqMapping : seqMappings) + { + StringBuilder newSequence = new StringBuilder(dnaSeq.getLength()); + + /* + * Get the codon regions as { [2, 5], [7, 12], [14, 14] etc } + */ + final List dnaExonRanges = seqMapping.getMap().getFromRanges(); + for (int[] range : dnaExonRanges) + { + for (int pos = range[0]; pos <= range[1]; pos++) + { + newSequence.append(dna[pos - 1]); + } + } + + SequenceI exon = new Sequence(dnaSeq.getName(), + newSequence.toString()); + + /* + * Locate any xrefs to CDS database on the protein product and attach to + * the CDS sequence. Also add as a sub-token of the sequence name. + */ + // default to "CDS" if we can't locate an actual gene id + String cdsAccId = FeatureProperties + .getCodingFeature(DBRefSource.EMBL); + DBRefEntry[] cdsRefs = DBRefUtils.selectRefs(seqMapping.getTo() + .getDBRef(), DBRefSource.CODINGDBS); + if (cdsRefs != null) + { + for (DBRefEntry cdsRef : cdsRefs) + { + exon.addDBRef(new DBRefEntry(cdsRef)); + cdsAccId = cdsRef.getAccessionId(); + } + } + exon.setName(exon.getName() + "|" + cdsAccId); + exon.createDatasetSequence(); + + /* + * Build new mappings - from the same protein regions, but now to + * contiguous exons + */ + List exonRange = new ArrayList(); + exonRange.add(new int[] { 1, newSequence.length() }); + MapList map = new MapList(exonRange, seqMapping.getMap() + .getToRanges(), 3, 1); + newMapping.addMap(exon.getDatasetSequence(), seqMapping.getTo(), map); + MapList cdsToDnaMap = new MapList(dnaExonRanges, exonRange, 1, 1); + newMapping.addMap(dnaSeq, exon.getDatasetSequence(), cdsToDnaMap); + + exonSequences.add(exon); + } + return exonSequences; + } }