X-Git-Url: http://source.jalview.org/gitweb/?a=blobdiff_plain;ds=sidebyside;f=src%2Fjalview%2Fanalysis%2FAlignmentUtils.java;h=db69823050fc191d5ebddb0cbd3baeba0a04e841;hb=9fe87bd08ab29b6fe53364f387d7a2e3a8d39994;hp=fe95dca15c2447de3218b2824ebb6f1c14e5c949;hpb=a6b324e3f5edac3df0b968f0037b1cc8b651598e;p=jalview.git diff --git a/src/jalview/analysis/AlignmentUtils.java b/src/jalview/analysis/AlignmentUtils.java index fe95dca..db69823 100644 --- a/src/jalview/analysis/AlignmentUtils.java +++ b/src/jalview/analysis/AlignmentUtils.java @@ -28,20 +28,27 @@ import jalview.datamodel.AlignmentI; import jalview.datamodel.DBRefEntry; import jalview.datamodel.DBRefSource; import jalview.datamodel.FeatureProperties; +import jalview.datamodel.IncompleteCodonException; import jalview.datamodel.Mapping; import jalview.datamodel.SearchResults; import jalview.datamodel.Sequence; import jalview.datamodel.SequenceFeature; import jalview.datamodel.SequenceGroup; import jalview.datamodel.SequenceI; +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; import java.util.ArrayList; import java.util.Arrays; import java.util.Collection; +import java.util.Collections; +import java.util.Comparator; import java.util.HashMap; import java.util.HashSet; import java.util.Iterator; @@ -49,6 +56,7 @@ 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.TreeMap; @@ -315,7 +323,7 @@ public class AlignmentUtils } else { - MapList map = mapProteinSequenceToCdna(aaSeq, cdnaSeq); + MapList map = mapCdnaToProtein(aaSeq, cdnaSeq); if (map != null) { acf.addMap(cdnaSeq, aaSeq, map); @@ -355,16 +363,22 @@ public class AlignmentUtils } /** - * 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. + * Builds a mapping (if possible) of a cDNA to a protein sequence. + * + * Returns null if no mapping is determined. * - * @param proteinSeqs + * @param proteinSeq + * the aligned protein sequence * @param cdnaSeq + * the aligned cdna sequence * @return */ - public static MapList mapProteinSequenceToCdna(SequenceI proteinSeq, + public static MapList mapCdnaToProtein(SequenceI proteinSeq, SequenceI cdnaSeq) { /* @@ -394,7 +408,7 @@ public class AlignmentUtils final int proteinEnd = proteinSeq.getEnd(); /* - * If lengths don't match, try ignoring stop codon. + * If lengths don't match, try ignoring stop codon (if present) */ if (cdnaLength != mappedLength && cdnaLength > 2) { @@ -425,17 +439,20 @@ public class AlignmentUtils cdnaLength -= 3; } - if (cdnaLength != mappedLength) - { - return null; - } - if (!translatesAs(cdnaSeqChars, startOffset, aaSeqChars)) + if (translatesAs(cdnaSeqChars, startOffset, aaSeqChars)) { - return null; + /* + * protein is translation of dna (+/- start/stop codons) + */ + MapList map = new MapList(new int[] { cdnaStart, cdnaEnd }, new int[] + { proteinStart, proteinEnd }, 3, 1); + return map; } - MapList map = new MapList(new int[] { cdnaStart, cdnaEnd }, new int[] { - proteinStart, proteinEnd }, 3, 1); - return map; + + /* + * translation failed - try mapping CDS annotated regions of dna + */ + return mapCdsToProtein(cdnaSeq, proteinSeq); } /** @@ -456,16 +473,18 @@ public class AlignmentUtils return false; } - int aaResidue = 0; - for (int i = cdnaStart; i < cdnaSeqChars.length - 2 - && aaResidue < aaSeqChars.length; i += 3, aaResidue++) + int aaPos = 0; + int dnaPos = cdnaStart; + for (; dnaPos < cdnaSeqChars.length - 2 + && aaPos < aaSeqChars.length; dnaPos += 3, aaPos++) { - String codon = String.valueOf(cdnaSeqChars, i, 3); + String codon = String.valueOf(cdnaSeqChars, dnaPos, 3); final String translated = ResidueProperties.codonTranslate(codon); + /* * allow * in protein to match untranslatable in dna */ - final char aaRes = aaSeqChars[aaResidue]; + final char aaRes = aaSeqChars[aaPos]; if ((translated == null || "STOP".equals(translated)) && aaRes == '*') { continue; @@ -478,8 +497,32 @@ public class AlignmentUtils return false; } } - // fail if we didn't match all of the aa sequence - return (aaResidue == aaSeqChars.length); + + /* + * check we matched all of the protein sequence + */ + if (aaPos != aaSeqChars.length) + { + return false; + } + + /* + * check we matched all of the dna except + * for optional trailing STOP codon + */ + if (dnaPos == cdnaSeqChars.length) + { + return true; + } + if (dnaPos == cdnaSeqChars.length - 3) + { + String codon = String.valueOf(cdnaSeqChars, dnaPos, 3); + if ("STOP".equals(ResidueProperties.codonTranslate(codon))) + { + return true; + } + } + return false; } /** @@ -924,6 +967,34 @@ public class AlignmentUtils public static int alignProteinAsDna(AlignmentI protein, AlignmentI dna) { List unmappedProtein = new ArrayList(); + Map> alignedCodons = buildCodonColumnsMap( + protein, dna, unmappedProtein); + return alignProteinAs(protein, alignedCodons, unmappedProtein); + } + + /** + * 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 + * the codons, and allows us to read off the peptides at each position in + * order to assemble 'aligned' protein sequences. + * + * @param protein + * the protein alignment + * @param dna + * the coding dna alignment + * @param unmappedProtein + * any unmapped proteins are added to this list + * @return + */ + protected static Map> buildCodonColumnsMap( + AlignmentI protein, AlignmentI dna, + List unmappedProtein) + { + /* + * maintain a list of any proteins with no mappings - these will be + * rendered 'as is' in the protein alignment as we can't align them + */ unmappedProtein.addAll(protein.getSequences()); List mappings = protein.getCodonFrames(); @@ -933,24 +1004,115 @@ 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()) { for (AlignedCodonFrame mapping : mappings) { - Mapping seqMap = mapping.getMappingForSequence(dnaSeq); SequenceI prot = mapping.findAlignedSequence( dnaSeq.getDatasetSequence(), protein); if (prot != null) { + Mapping seqMap = mapping.getMappingForSequence(dnaSeq); addCodonPositions(dnaSeq, prot, protein.getGapCharacter(), seqMap, alignedCodons); unmappedProtein.remove(prot); } } } - return alignProteinAs(protein, alignedCodons, unmappedProtein); + + /* + * Finally add any unmapped peptide start residues (e.g. for incomplete + * codons) as if at the codon position before the second residue + */ + int mappedSequenceCount = protein.getHeight() - unmappedProtein.size(); + addUnmappedPeptideStarts(alignedCodons, mappedSequenceCount); + + return alignedCodons; + } + + /** + * Scans for any protein mapped from position 2 (meaning unmapped start + * position e.g. an incomplete codon), and synthesizes a 'codon' for it at the + * preceding position in the alignment + * + * @param alignedCodons + * the codon-to-peptide map + * @param mappedSequenceCount + * the number of distinct sequences in the map + */ + protected static void addUnmappedPeptideStarts( + Map> alignedCodons, + int mappedSequenceCount) + { + // TODO delete this ugly hack once JAL-2022 is resolved + // i.e. we can model startPhase > 0 (incomplete start codon) + + List sequencesChecked = new ArrayList(); + AlignedCodon lastCodon = null; + Map toAdd = new HashMap(); + + for (Entry> entry : alignedCodons + .entrySet()) + { + for (Entry sequenceCodon : entry.getValue() + .entrySet()) + { + SequenceI seq = sequenceCodon.getKey(); + if (sequencesChecked.contains(seq)) + { + continue; + } + sequencesChecked.add(seq); + AlignedCodon codon = sequenceCodon.getValue(); + if (codon.peptideCol > 1) + { + System.err + .println("Problem mapping protein with >1 unmapped start positions: " + + seq.getName()); + } + else if (codon.peptideCol == 1) + { + /* + * first position (peptideCol == 0) was unmapped - add it + */ + if (lastCodon != null) + { + AlignedCodon firstPeptide = new AlignedCodon(lastCodon.pos1, + lastCodon.pos2, lastCodon.pos3, String.valueOf(seq + .getCharAt(0)), 0); + toAdd.put(seq, firstPeptide); + } + else + { + /* + * unmapped residue at start of alignment (no prior column) - + * 'insert' at nominal codon [0, 0, 0] + */ + AlignedCodon firstPeptide = new AlignedCodon(0, 0, 0, + String.valueOf(seq.getCharAt(0)), 0); + toAdd.put(seq, firstPeptide); + } + } + if (sequencesChecked.size() == mappedSequenceCount) + { + // no need to check past first mapped position in all sequences + break; + } + } + lastCodon = entry.getKey(); + } + + /* + * add any new codons safely after iterating over the map + */ + for (Entry startCodon : toAdd.entrySet()) + { + addCodonToMap(alignedCodons, startCodon.getValue(), + startCodon.getKey()); + } } /** @@ -965,7 +1127,7 @@ public class AlignmentUtils * @return */ protected static int alignProteinAs(AlignmentI protein, - Map> alignedCodons, + Map> alignedCodons, List unmappedProtein) { /* @@ -987,12 +1149,13 @@ public class AlignmentUtils int column = 0; for (AlignedCodon codon : alignedCodons.keySet()) { - final Map columnResidues = alignedCodons + final Map columnResidues = alignedCodons .get(codon); - for (Entry entry : columnResidues.entrySet()) + for (Entry entry : columnResidues.entrySet()) { // place translated codon at its column position in sequence - entry.getKey().getSequence()[column] = entry.getValue().charAt(0); + entry.getKey().getSequence()[column] = entry.getValue().product + .charAt(0); } column++; } @@ -1017,23 +1180,51 @@ public class AlignmentUtils */ static void addCodonPositions(SequenceI dna, SequenceI protein, char gapChar, Mapping seqMap, - Map> alignedCodons) + Map> alignedCodons) { Iterator codons = seqMap.getCodonIterator(dna, gapChar); + + /* + * add codon positions, and their peptide translations, to the alignment + * map, while remembering the first codon mapped + */ while (codons.hasNext()) { - AlignedCodon codon = codons.next(); - Map seqProduct = alignedCodons.get(codon); - if (seqProduct == null) + try + { + AlignedCodon codon = codons.next(); + addCodonToMap(alignedCodons, codon, protein); + } catch (IncompleteCodonException e) { - seqProduct = new HashMap(); - alignedCodons.put(codon, seqProduct); + // possible incomplete trailing codon - ignore + } catch (NoSuchElementException e) + { + // possibly peptide lacking STOP } - seqProduct.put(protein, codon.product); } } /** + * Helper method to add a codon-to-peptide entry to the aligned codons map + * + * @param alignedCodons + * @param codon + * @param protein + */ + protected static void addCodonToMap( + Map> alignedCodons, + AlignedCodon codon, SequenceI protein) + { + Map seqProduct = alignedCodons.get(codon); + if (seqProduct == null) + { + seqProduct = new HashMap(); + alignedCodons.put(codon, seqProduct); + } + seqProduct.put(protein, codon); + } + + /** * 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: @@ -1116,7 +1307,7 @@ public class AlignmentUtils * Just try to make a mapping (it is not yet stored), test whether * successful. */ - return mapProteinSequenceToCdna(proteinDs, dnaDs) != null; + return mapCdnaToProtein(proteinDs, dnaDs) != null; } /** @@ -1318,21 +1509,31 @@ public class AlignmentUtils } /** - * Constructs an alignment consisting of the mapped cds regions in the given - * nucleotide sequences, and updates mappings to match. + * Constructs an alignment consisting of the mapped (CDS) regions in the given + * nucleotide sequences, and updates mappings to match. The new sequences are + * aligned as per the original sequence, with entirely gapped columns (codon + * interrupted by intron) omitted. * * @param dna * aligned dna sequences * @param mappings * from dna to protein; these are replaced with new mappings + * @param al * @return an alignment whose sequences are the cds-only parts of the dna - * sequences (or null if no cds are found) + * sequences (or null if no mappings are found) */ public static AlignmentI makeCdsAlignment(SequenceI[] dna, - List mappings) + List mappings, AlignmentI al) { + List cdsColumns = findCdsColumns(dna); + + /* + * create CDS sequences and new mappings + * (from cdna to cds, and cds to peptide) + */ List newMappings = new ArrayList(); List cdsSequences = new ArrayList(); + char gap = al.getGapCharacter(); for (SequenceI dnaSeq : dna) { @@ -1342,8 +1543,8 @@ public class AlignmentUtils for (AlignedCodonFrame acf : seqMappings) { AlignedCodonFrame newMapping = new AlignedCodonFrame(); - final List mappedCds = makeCdsSequences(ds, acf, - newMapping); + final List mappedCds = makeCdsSequences(dnaSeq, acf, + cdsColumns, newMapping, gap); if (!mappedCds.isEmpty()) { cdsSequences.addAll(mappedCds); @@ -1351,9 +1552,21 @@ public class AlignmentUtils } } } - AlignmentI al = new Alignment( + AlignmentI newAl = new Alignment( cdsSequences.toArray(new SequenceI[cdsSequences.size()])); - al.setDataset(null); + + /* + * add new sequences to the shared dataset, set it on the new alignment + */ + List dsseqs = al.getDataset().getSequences(); + for (SequenceI seq : newAl.getSequences()) + { + if (!dsseqs.contains(seq.getDatasetSequence())) + { + dsseqs.add(seq.getDatasetSequence()); + } + } + newAl.setDataset(al.getDataset()); /* * Replace the old mappings with the new ones @@ -1361,7 +1574,128 @@ public class AlignmentUtils mappings.clear(); mappings.addAll(newMappings); - return al; + return newAl; + } + + /** + * Returns a consolidated list of column ranges where at least one sequence + * has a CDS feature. This assumes CDS features are on genomic sequence i.e. + * are for contiguous CDS ranges (no gaps). + * + * @param seqs + * @return + */ + public static List findCdsColumns(SequenceI[] seqs) + { + // TODO use refactored code from AlignViewController + // markColumnsContainingFeatures, not reinvent the wheel! + + List result = new ArrayList(); + for (SequenceI seq : seqs) + { + result.addAll(findCdsColumns(seq)); + } + + /* + * sort and compact the list into ascending, non-overlapping ranges + */ + Collections.sort(result, new Comparator() + { + @Override + public int compare(int[] o1, int[] o2) + { + return Integer.compare(o1[0], o2[0]); + } + }); + result = MapList.coalesceRanges(result); + + return result; + } + + public static List findCdsColumns(SequenceI seq) + { + List result = new ArrayList(); + SequenceOntologyI so = SequenceOntologyFactory.getInstance(); + SequenceFeature[] sfs = seq.getSequenceFeatures(); + if (sfs != null) + { + for (SequenceFeature sf : sfs) + { + if (so.isA(sf.getType(), SequenceOntologyI.CDS)) + { + int colStart = seq.findIndex(sf.getBegin()); + int colEnd = seq.findIndex(sf.getEnd()); + result.add(new int[] { colStart, colEnd }); + } + } + } + return result; + } + + /** + * Answers true if all sequences have a gap at (or do not extend to) the + * specified column position (base 1) + * + * @param seqs + * @param col + * @return + */ + public static boolean isGappedColumn(List seqs, int col) + { + if (seqs != null) + { + for (SequenceI seq : seqs) + { + if (!Comparison.isGap(seq.getCharAt(col - 1))) + { + return false; + } + } + } + return true; + } + + /** + * Returns the column ranges (base 1) of each aligned sequence that are + * involved in any mapping. This is a helper method for aligning protein + * products of aligned transcripts. + * + * @param mappedSequences + * (possibly gapped) dna sequences + * @param mappings + * @return + */ + protected static List> getMappedColumns( + List mappedSequences, List mappings) + { + List> result = new ArrayList>(); + for (SequenceI seq : mappedSequences) + { + List columns = new ArrayList(); + List seqMappings = MappingUtils + .findMappingsForSequence(seq, mappings); + for (AlignedCodonFrame mapping : seqMappings) + { + List maps = mapping.getMappingsForSequence(seq); + for (Mapping map : maps) + { + /* + * Get the codon regions as { [2, 5], [7, 12], [14, 14] etc } + * Find and add the overall aligned column range for each + */ + for (int[] cdsRange : map.getMap().getFromRanges()) + { + int startPos = cdsRange[0]; + int endPos = cdsRange[1]; + int startCol = seq.findIndex(startPos); + int endCol = seq.findIndex(endPos); + columns.add(new int[] { startCol, endCol }); + } + } + } + result.add(columns); + } + return result; } /** @@ -1378,51 +1712,59 @@ public class AlignmentUtils * (example EMBL KF591215). * * @param dnaSeq - * a dna dataset sequence + * a dna aligned sequence * @param mapping * containing one or more mappings of the sequence to protein + * @param ungappedCdsColumns * @param newMappings * the new mapping to populate, from the cds-only sequences to their * mapped protein sequences * @return */ protected static List makeCdsSequences(SequenceI dnaSeq, - AlignedCodonFrame mapping, AlignedCodonFrame newMappings) + AlignedCodonFrame mapping, List ungappedCdsColumns, + AlignedCodonFrame newMappings, char gapChar) { List cdsSequences = new ArrayList(); List seqMappings = mapping.getMappingsForSequence(dnaSeq); for (Mapping seqMapping : seqMappings) { - SequenceI cds = makeCdsSequence(dnaSeq, seqMapping); + SequenceI cds = makeCdsSequence(dnaSeq, seqMapping, + ungappedCdsColumns, gapChar); + cds.createDatasetSequence(); cdsSequences.add(cds); /* * add new mappings, from dna to cds, and from cds to peptide */ - MapList dnaToCds = addCdsMappings(dnaSeq, cds, seqMapping, - newMappings); + MapList dnaToCds = addCdsMappings(dnaSeq.getDatasetSequence(), cds, + seqMapping, newMappings); /* * transfer any features on dna that overlap the CDS */ - transferFeatures(dnaSeq, cds, dnaToCds, "CDS" /* SequenceOntology.CDS */); + transferFeatures(dnaSeq, cds, dnaToCds, null, SequenceOntologyI.CDS); } return cdsSequences; } /** - * Transfers any co-located features on 'fromSeq' to 'toSeq', adjusting the + * Transfers co-located features on 'fromSeq' to 'toSeq', adjusting the * feature start/end ranges, optionally omitting specified feature types. + * Returns the number of features copied. * * @param fromSeq * @param toSeq + * @param select + * if not null, only features of this type are copied (including + * subtypes in the Sequence Ontology) * @param mapping * the mapping from 'fromSeq' to 'toSeq' * @param omitting */ - protected static void transferFeatures(SequenceI fromSeq, - SequenceI toSeq, MapList mapping, String... omitting) + public static int transferFeatures(SequenceI fromSeq, SequenceI toSeq, + MapList mapping, String select, String... omitting) { SequenceI copyTo = toSeq; while (copyTo.getDatasetSequence() != null) @@ -1430,12 +1772,18 @@ public class AlignmentUtils copyTo = copyTo.getDatasetSequence(); } + SequenceOntologyI so = SequenceOntologyFactory.getInstance(); + int count = 0; SequenceFeature[] sfs = fromSeq.getSequenceFeatures(); if (sfs != null) { for (SequenceFeature sf : sfs) { String type = sf.getType(); + if (select != null && !so.isA(type, select)) + { + continue; + } boolean omit = false; for (String toOmit : omitting) { @@ -1453,16 +1801,48 @@ public class AlignmentUtils * locate the mapped range - null if either start or end is * not mapped (no partial overlaps are calculated) */ - int[] mappedTo = mapping.locateInTo(sf.getBegin(), sf.getEnd()); + int start = sf.getBegin(); + int end = sf.getEnd(); + int[] mappedTo = mapping.locateInTo(start, end); + /* + * if whole exon range doesn't map, try interpreting it + * as 5' or 3' exon overlapping the CDS range + */ + if (mappedTo == null) + { + mappedTo = mapping.locateInTo(end, end); + if (mappedTo != null) + { + /* + * end of exon is in CDS range - 5' overlap + * to a range from the start of the peptide + */ + mappedTo[0] = 1; + } + } + if (mappedTo == null) + { + mappedTo = mapping.locateInTo(start, start); + if (mappedTo != null) + { + /* + * start of exon is in CDS range - 3' overlap + * to a range up to the end of the peptide + */ + mappedTo[1] = toSeq.getLength(); + } + } if (mappedTo != null) { SequenceFeature copy = new SequenceFeature(sf); copy.setBegin(Math.min(mappedTo[0], mappedTo[1])); copy.setEnd(Math.max(mappedTo[0], mappedTo[1])); copyTo.addSequenceFeature(copy); + count++; } } } + return count; } /** @@ -1480,8 +1860,8 @@ public class AlignmentUtils * @return */ protected static MapList addCdsMappings(SequenceI dnaSeq, - SequenceI cdsSeq, - Mapping dnaMapping, AlignedCodonFrame newMappings) + SequenceI cdsSeq, Mapping dnaMapping, + AlignedCodonFrame newMappings) { cdsSeq.createDatasetSequence(); @@ -1490,18 +1870,18 @@ public class AlignmentUtils * the peptide ranges taken unchanged from the dna mapping */ List cdsRanges = new ArrayList(); - cdsRanges.add(new int[] { 1, cdsSeq.getLength() }); + SequenceI cdsDataset = cdsSeq.getDatasetSequence(); + cdsRanges.add(new int[] { 1, cdsDataset.getLength() }); MapList cdsToPeptide = new MapList(cdsRanges, dnaMapping.getMap() .getToRanges(), 3, 1); - newMappings.addMap(cdsSeq.getDatasetSequence(), dnaMapping.getTo(), - cdsToPeptide); + newMappings.addMap(cdsDataset, dnaMapping.getTo(), cdsToPeptide); /* * dna 'from' ranges map 1:1 to the contiguous extracted CDS */ - MapList dnaToCds = new MapList( - dnaMapping.getMap().getFromRanges(), cdsRanges, 1, 1); - newMappings.addMap(dnaSeq, cdsSeq.getDatasetSequence(), dnaToCds); + MapList dnaToCds = new MapList(dnaMapping.getMap().getFromRanges(), + cdsRanges, 1, 1); + newMappings.addMap(dnaSeq, cdsDataset, dnaToCds); return dnaToCds; } @@ -1513,34 +1893,52 @@ public class AlignmentUtils * nucleotide sequence * @param seqMapping * mappings from CDS regions of nucleotide + * @param ungappedCdsColumns * @return */ protected static SequenceI makeCdsSequence(SequenceI dnaSeq, - Mapping seqMapping) + Mapping seqMapping, List ungappedCdsColumns, char gapChar) { - StringBuilder newSequence = new StringBuilder(dnaSeq.getLength()); - final char[] dna = dnaSeq.getSequence(); - int offset = dnaSeq.getStart() - 1; + int cdsWidth = MappingUtils.getLength(ungappedCdsColumns); /* - * Get the codon regions as { [2, 5], [7, 12], [14, 14] etc } + * populate CDS columns with the aligned + * column character if that column is mapped (which may be a gap + * if an intron interrupts a codon), else with a gap */ - final List dnaCdsRanges = seqMapping.getMap().getFromRanges(); - for (int[] range : dnaCdsRanges) + List fromRanges = seqMapping.getMap().getFromRanges(); + char[] cdsChars = new char[cdsWidth]; + int pos = 0; + for (int[] columns : ungappedCdsColumns) { - // TODO handle reverse mapping as well (range[1] < range[0]) - for (int pos = range[0]; pos <= range[1]; pos++) + for (int i = columns[0]; i <= columns[1]; i++) { - newSequence.append(dna[pos - offset - 1]); + char dnaChar = dnaSeq.getCharAt(i - 1); + if (Comparison.isGap(dnaChar)) + { + cdsChars[pos] = gapChar; + } + else + { + int seqPos = dnaSeq.findPosition(i - 1); + if (MappingUtils.contains(fromRanges, seqPos)) + { + cdsChars[pos] = dnaChar; + } + else + { + cdsChars[pos] = gapChar; + } + } + pos++; } } + SequenceI cdsSequence = new Sequence(dnaSeq.getName(), + String.valueOf(cdsChars)); - SequenceI cds = new Sequence(dnaSeq.getName(), - newSequence.toString()); + transferDbRefs(seqMapping.getTo(), cdsSequence); - transferDbRefs(seqMapping.getTo(), cds); - - return cds; + return cdsSequence; } /** @@ -1568,4 +1966,349 @@ public class AlignmentUtils to.setName(to.getName() + "|" + cdsAccId); } } + + /** + * Returns a mapping from dna to protein by inspecting sequence features of + * type "CDS" on the dna. + * + * @param dnaSeq + * @param proteinSeq + * @return + */ + public static MapList mapCdsToProtein(SequenceI dnaSeq, + SequenceI proteinSeq) + { + List ranges = findCdsPositions(dnaSeq); + int mappedDnaLength = MappingUtils.getLength(ranges); + + int proteinLength = proteinSeq.getLength(); + int proteinStart = proteinSeq.getStart(); + int proteinEnd = proteinSeq.getEnd(); + + /* + * incomplete start codon may mean X at start of peptide + * we ignore both for mapping purposes + */ + if (proteinSeq.getCharAt(0) == 'X') + { + // todo JAL-2022 support startPhase > 0 + proteinStart++; + proteinLength--; + } + List proteinRange = new ArrayList(); + + /* + * dna length should map to protein (or protein plus stop codon) + */ + int codesForResidues = mappedDnaLength / 3; + if (codesForResidues == (proteinLength + 1)) + { + // assuming extra codon is for STOP and not in peptide + codesForResidues--; + } + if (codesForResidues == proteinLength) + { + proteinRange.add(new int[] { proteinStart, proteinEnd }); + return new MapList(ranges, proteinRange, 3, 1); + } + return null; + } + + /** + * 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 + * CDS in the Sequence Ontology) + * + * @param dnaSeq + * @return + */ + public static List findCdsPositions(SequenceI dnaSeq) + { + List result = new ArrayList(); + SequenceFeature[] sfs = dnaSeq.getSequenceFeatures(); + if (sfs == null) + { + return result; + } + SequenceOntologyI so = SequenceOntologyFactory.getInstance(); + for (SequenceFeature sf : sfs) + { + /* + * process a CDS feature (or a sub-type of CDS) + */ + if (so.isA(sf.getType(), SequenceOntologyI.CDS)) + { + int phase = 0; + try { + phase = Integer.parseInt(sf.getPhase()); + } catch (NumberFormatException e) + { + // ignore + } + /* + * phase > 0 on first codon means 5' incomplete - skip to the start + * of the next codon; example ENST00000496384 + */ + int begin = sf.getBegin(); + int end = sf.getEnd(); + if (result.isEmpty()) + { + // TODO JAL-2022 support start phase > 0 + begin += phase; + if (begin > end) + { + continue; // shouldn't happen? + } + } + result.add(new int[] { begin, end }); + } + } + return result; + } + + /** + * Maps exon features from dna to protein, and computes variants in peptide + * product generated by variants in dna, and adds them as sequence_variant + * features on the protein sequence. Returns the number of variant features + * added. + * + * @param dnaSeq + * @param peptide + * @param dnaToProtein + */ + 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); + + LinkedHashMap variants = buildDnaVariantsMap( + dnaSeq, dnaToProtein); + + /* + * scan codon variations, compute peptide variants and add to peptide sequence + */ + int count = 0; + for (Entry variant : variants.entrySet()) + { + int peptidePos = variant.getKey(); + String[][] codonVariants = variant.getValue(); + String residue = String.valueOf(peptide.getCharAt(peptidePos - 1)); // 0-based + List peptideVariants = computePeptideVariants(codonVariants, + residue); + if (!peptideVariants.isEmpty()) + { + String desc = StringUtils.listToDelimitedString(peptideVariants, + ", "); + SequenceFeature sf = new SequenceFeature( + SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos, + peptidePos, 0f, null); + peptide.addSequenceFeature(sf); + count++; + } + } + + /* + * ugly sort to get sequence features in start position order + * - would be better to store in Sequence as a TreeSet instead? + */ + Arrays.sort(peptide.getSequenceFeatures(), + new Comparator() + { + @Override + public int compare(SequenceFeature o1, SequenceFeature o2) + { + int c = Integer.compare(o1.getBegin(), o2.getBegin()); + return c == 0 ? Integer.compare(o1.getEnd(), o2.getEnd()) + : c; + } + }); + return count; + } + + /** + * Builds a map whose key is position in the protein sequence, and value is an + * array of all variants for the coding codon positions + * + * @param dnaSeq + * @param dnaToProtein + * @return + */ + static LinkedHashMap buildDnaVariantsMap( + SequenceI dnaSeq, MapList dnaToProtein) + { + /* + * map from peptide position to all variant features of the codon for it + * LinkedHashMap ensures we add the peptide features in sequence order + */ + LinkedHashMap variants = new LinkedHashMap(); + SequenceOntologyI so = SequenceOntologyFactory.getInstance(); + + SequenceFeature[] dnaFeatures = dnaSeq.getSequenceFeatures(); + if (dnaFeatures == null) + { + return variants; + } + + int dnaStart = dnaSeq.getStart(); + int[] lastCodon = null; + int lastPeptidePostion = 0; + + /* + * build a map of codon variations for peptides + */ + for (SequenceFeature sf : dnaFeatures) + { + int dnaCol = sf.getBegin(); + if (dnaCol != sf.getEnd()) + { + // not handling multi-locus variant features + continue; + } + if (so.isA(sf.getType(), SequenceOntologyI.SEQUENCE_VARIANT)) + { + int[] mapsTo = dnaToProtein.locateInTo(dnaCol, dnaCol); + if (mapsTo == null) + { + // feature doesn't lie within coding region + continue; + } + int peptidePosition = mapsTo[0]; + String[][] codonVariants = variants.get(peptidePosition); + if (codonVariants == null) + { + codonVariants = new String[3][]; + variants.put(peptidePosition, codonVariants); + } + + /* + * extract dna variants to a string array + */ + String alls = (String) sf.getValue("alleles"); + if (alls == null) + { + continue; + } + String[] alleles = alls.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 this variant) for each codon position + */ + for (int codonPos = 0; codonPos < 3; codonPos++) + { + String nucleotide = String.valueOf( + dnaSeq.getCharAt(codon[codonPos] - dnaStart)) + .toUpperCase(); + if (codonVariants[codonPos] == null) + { + /* + * record current dna base + */ + codonVariants[codonPos] = new String[] { nucleotide }; + } + if (codon[codonPos] == dnaCol) + { + /* + * add alleles to dna base (and any previously found alleles) + */ + String[] known = codonVariants[codonPos]; + String[] dnaVariants = new String[alleles.length + known.length]; + System.arraycopy(known, 0, dnaVariants, 0, known.length); + System.arraycopy(alleles, 0, dnaVariants, known.length, + alleles.length); + codonVariants[codonPos] = dnaVariants; + } + } + } + } + return variants; + } + + /** + * Returns a sorted, non-redundant list of all peptide translations generated + * by the given dna variants, excluding the current residue value + * + * @param codonVariants + * an array of base values (acgtACGT) for codon positions 1, 2, 3 + * @param residue + * the current residue translation + * @return + */ + static List computePeptideVariants( + String[][] codonVariants, String residue) + { + List result = new ArrayList(); + for (String base1 : codonVariants[0]) + { + for (String base2 : codonVariants[1]) + { + for (String base3 : codonVariants[2]) + { + String codon = base1 + base2 + base3; + /* + * 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 ignored here + */ + String peptide = codon.contains("-") ? "-" + : (codon.length() > 3 ? null : ResidueProperties + .codonTranslate(codon)); + if (peptide != null && !result.contains(peptide) + && !peptide.equalsIgnoreCase(residue)) + { + result.add(peptide); + } + } + } + } + + /* + * sort alphabetically with STOP at the end + */ + Collections.sort(result, new Comparator() + { + + @Override + public int compare(String o1, String o2) + { + if ("STOP".equals(o1)) + { + return 1; + } + else if ("STOP".equals(o2)) + { + return -1; + } + else + { + return o1.compareTo(o2); + } + } + }); + return result; + } }