/*
- * Jalview - A Sequence Alignment Editor and Viewer (Version 2.8.2b1)
- * Copyright (C) 2014 The Jalview Authors
+ * Jalview - A Sequence Alignment Editor and Viewer ($$Version-Rel$$)
+ * Copyright (C) $$Year-Rel$$ The Jalview Authors
*
* This file is part of Jalview.
*
*/
package jalview.analysis;
+import static jalview.io.gff.GffConstants.CLINICAL_SIGNIFICANCE;
+
+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;
+import jalview.datamodel.DBRefEntry;
+import jalview.datamodel.IncompleteCodonException;
+import jalview.datamodel.Mapping;
+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.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.Comparator;
+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.TreeMap;
/**
* grab bag of useful alignment manipulation operations Expect these to be
public class AlignmentUtils
{
+ private static final int CODON_LENGTH = 3;
+
+ private static final String SEQUENCE_VARIANT = "sequence_variant:";
+
+ private static final String ID = "ID";
+
+ /**
+ * A data model to hold the 'normal' base value at a position, and an optional
+ * sequence variant feature
+ */
+ static final class DnaVariant
+ {
+ final String base;
+
+ SequenceFeature variant;
+
+ DnaVariant(String nuc)
+ {
+ base = nuc;
+ variant = null;
+ }
+
+ DnaVariant(String nuc, SequenceFeature var)
+ {
+ base = nuc;
+ variant = var;
+ }
+
+ public String getSource()
+ {
+ return variant == null ? null : variant.getFeatureGroup();
+ }
+ }
+
/**
* given an existing alignment, create a new alignment including all, or up to
* flankSize additional symbols from each sequence's dataset sequence
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;
}
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
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);
{
for (AlignmentAnnotation aa : s.getAnnotation())
{
+ aa.adjustForAlignment(); // JAL-1712 fix
newAl.addAnnotation(aa);
}
}
}
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<String, List<SequenceI>> getSequencesByName(
+ AlignmentI al)
+ {
+ Map<String, List<SequenceI>> theMap = new LinkedHashMap<String, List<SequenceI>>();
+ for (SequenceI seq : al.getSequences())
+ {
+ String name = seq.getName();
+ if (name != null)
+ {
+ List<SequenceI> seqs = theMap.get(name);
+ if (seqs == null)
+ {
+ seqs = new ArrayList<SequenceI>();
+ 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<SequenceI> mappedDna = new HashSet<SequenceI>();
+ Set<SequenceI> mappedProtein = new HashSet<SequenceI>();
+
+ /*
+ * 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<SequenceI> mappedDna,
+ Set<SequenceI> mappedProtein, boolean xrefsOnly)
+ {
+ boolean mappingExistsOrAdded = false;
+ List<SequenceI> 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 = mapCdnaToProtein(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(List<AlignedCodonFrame> mappings,
+ SequenceI aaSeq, SequenceI cdnaSeq)
+ {
+ if (mappings != null)
+ {
+ for (AlignedCodonFrame acf : mappings)
+ {
+ if (cdnaSeq == acf.getDnaForAaSeq(aaSeq))
+ {
+ return true;
+ }
+ }
+ }
+ return false;
+ }
+
+ /**
+ * Builds a mapping (if possible) of a cDNA to a protein sequence.
+ * <ul>
+ * <li>first checks if the cdna translates exactly to the protein sequence</li>
+ * <li>else checks for translation after removing a STOP codon</li>
+ * <li>else checks for translation after removing a START codon</li>
+ * <li>if that fails, inspect CDS features on the cDNA sequence</li>
+ * </ul>
+ * Returns null if no mapping is determined.
+ *
+ * @param proteinSeq
+ * the aligned protein sequence
+ * @param cdnaSeq
+ * the aligned cdna sequence
+ * @return
+ */
+ public static MapList mapCdnaToProtein(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 = CODON_LENGTH * 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 present)
+ */
+ if (cdnaLength != mappedLength && cdnaLength > 2)
+ {
+ String lastCodon = String.valueOf(cdnaSeqChars,
+ cdnaLength - CODON_LENGTH, CODON_LENGTH).toUpperCase();
+ for (String stop : ResidueProperties.STOP)
+ {
+ if (lastCodon.equals(stop))
+ {
+ cdnaEnd -= CODON_LENGTH;
+ cdnaLength -= CODON_LENGTH;
+ break;
+ }
+ }
+ }
+
+ /*
+ * If lengths still don't match, try ignoring start codon.
+ */
+ int startOffset = 0;
+ if (cdnaLength != mappedLength
+ && cdnaLength > 2
+ && String.valueOf(cdnaSeqChars, 0, CODON_LENGTH).toUpperCase()
+ .equals(ResidueProperties.START))
+ {
+ startOffset += CODON_LENGTH;
+ cdnaStart += CODON_LENGTH;
+ cdnaLength -= CODON_LENGTH;
+ }
+
+ if (translatesAs(cdnaSeqChars, startOffset, aaSeqChars))
+ {
+ /*
+ * protein is translation of dna (+/- start/stop codons)
+ */
+ MapList map = new MapList(new int[] { cdnaStart, cdnaEnd }, new int[]
+ { proteinStart, proteinEnd }, CODON_LENGTH, 1);
+ return map;
+ }
+
+ /*
+ * translation failed - try mapping CDS annotated regions of dna
+ */
+ return mapCdsToProtein(cdnaSeq, proteinSeq);
+ }
+
+ /**
+ * 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 aaPos = 0;
+ int dnaPos = cdnaStart;
+ for (; dnaPos < cdnaSeqChars.length - 2 && aaPos < aaSeqChars.length; dnaPos += CODON_LENGTH, aaPos++)
+ {
+ String codon = String.valueOf(cdnaSeqChars, dnaPos, CODON_LENGTH);
+ final String translated = ResidueProperties.codonTranslate(codon);
+
+ /*
+ * allow * in protein to match untranslatable in dna
+ */
+ final char aaRes = aaSeqChars[aaPos];
+ 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;
+ }
+ }
+
+ /*
+ * 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 - CODON_LENGTH)
+ {
+ String codon = String.valueOf(cdnaSeqChars, dnaPos, CODON_LENGTH);
+ if ("STOP".equals(ResidueProperties.codonTranslate(codon)))
+ {
+ return true;
+ }
+ }
+ return false;
+ }
+
+ /**
+ * 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<AlignedCodonFrame> 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 like more than one
+ * sequence).
+ */
+ SequenceI alignFrom = null;
+ AlignedCodonFrame mapping = null;
+ for (AlignedCodonFrame mp : mappings)
+ {
+ alignFrom = mp.findAlignedSequence(seq, 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 between
+ * intron 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
+
+ // 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();
+
+ int fromOffset = alignFrom.getStart() - 1;
+ int toOffset = alignTo.getStart() - 1;
+ int sourceGapMappedLength = 0;
+ boolean inExon = false;
+ final char[] thisSeq = alignTo.getSequence();
+ final char[] thatAligned = alignFrom.getSequence();
+ StringBuilder thisAligned = new StringBuilder(2 * thisSeq.length);
+
+ /*
+ * Traverse the 'model' aligned sequence
+ */
+ for (char sourceChar : thatAligned)
+ {
+ if (sourceChar == sourceGap)
+ {
+ sourceGapMappedLength += ratio;
+ continue;
+ }
+
+ /*
+ * Found a non-gap character. Locate its mapped region if any.
+ */
+ sourceDsPos++;
+ // Note mapping positions are base 1, our sequence positions base 0
+ int[] mappedPos = mapping.getMappedRegion(alignTo, alignFrom,
+ sourceDsPos + fromOffset);
+ if (mappedPos == null)
+ {
+ /*
+ * unmapped position; treat like a gap
+ */
+ sourceGapMappedLength += ratio;
+ // System.err.println("Can't align: no codon mapping to residue "
+ // + sourceDsPos + "(" + sourceChar + ")");
+ // return;
+ continue;
+ }
+
+ 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 model aligned sequence. Copy any remaining target sequence, optionally
+ * including (intron) gaps.
+ */
+ while (thisSeqPos < thisSeq.length)
+ {
+ final char c = thisSeq[thisSeqPos++];
+ if (c != myGapChar || preserveUnmappedGaps)
+ {
+ thisAligned.append(c);
+ }
+ sourceGapMappedLength--;
+ }
+
+ /*
+ * finally add gaps to pad for any trailing source gaps or
+ * unmapped characters
+ */
+ if (preserveUnmappedGaps)
+ {
+ while (sourceGapMappedLength > 0)
+ {
+ thisAligned.append(myGapChar);
+ sourceGapMappedLength--;
+ }
+ }
+
+ /*
+ * 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;
+ }
+
+ /**
+ * 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)
+ {
+ if (protein.isNucleotide() || !dna.isNucleotide())
+ {
+ System.err.println("Wrong alignment type in alignProteinAsDna");
+ return 0;
+ }
+ List<SequenceI> unmappedProtein = new ArrayList<SequenceI>();
+ Map<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons = buildCodonColumnsMap(
+ protein, dna, unmappedProtein);
+ return alignProteinAs(protein, alignedCodons, unmappedProtein);
+ }
+
+ /**
+ * Realigns the given dna to match the alignment of the protein, using codon
+ * mappings to translate aligned peptide positions to codons.
+ *
+ * Always produces a padded CDS alignment.
+ *
+ * @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<AlignedCodonFrame> mappings = protein.getCodonFrames();
+ int alignedCount = 0;
+ int width = 0; // alignment width for padding CDS
+ for (SequenceI dnaSeq : dna.getSequences())
+ {
+ if (alignCdsSequenceAsProtein(dnaSeq, protein, mappings,
+ dna.getGapCharacter()))
+ {
+ alignedCount++;
+ }
+ width = Math.max(dnaSeq.getLength(), width);
+ }
+ int oldwidth;
+ int diff;
+ for (SequenceI dnaSeq : dna.getSequences())
+ {
+ oldwidth = dnaSeq.getLength();
+ diff = width - oldwidth;
+ if (diff > 0)
+ {
+ dnaSeq.insertCharAt(oldwidth, diff, dna.getGapCharacter());
+ }
+ }
+ 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<AlignedCodonFrame> mappings, char gapChar)
+ {
+ SequenceI cdsDss = cdsSeq.getDatasetSequence();
+ if (cdsDss == null)
+ {
+ System.err
+ .println("alignCdsSequenceAsProtein needs aligned sequence!");
+ return false;
+ }
+
+ List<AlignedCodonFrame> dnaMappings = MappingUtils
+ .findMappingsForSequence(cdsSeq, mappings);
+ for (AlignedCodonFrame mapping : dnaMappings)
+ {
+ SequenceI peptide = mapping.findAlignedSequence(cdsSeq, protein);
+ if (peptide != null)
+ {
+ int peptideLength = peptide.getLength();
+ 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
+ * CODON_LENGTH + CODON_LENGTH)
+ || (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 * CODON_LENGTH
+ + (addStopCodon ? CODON_LENGTH : 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 += CODON_LENGTH;
+ }
+ else
+ {
+ proteinPos++;
+ int[] codon = mapList.locateInTo(proteinPos, proteinPos);
+ if (codon == null)
+ {
+ // e.g. incomplete start codon, X in peptide
+ cdsCol += CODON_LENGTH;
+ }
+ 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 - CODON_LENGTH)
+ {
+ 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 - CODON_LENGTH; 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
+ * 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<AlignedCodon, Map<SequenceI, AlignedCodon>> buildCodonColumnsMap(
+ AlignmentI protein, AlignmentI dna,
+ List<SequenceI> 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<AlignedCodonFrame> 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<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons = new TreeMap<AlignedCodon, Map<SequenceI, AlignedCodon>>(
+ new CodonComparator());
+
+ for (SequenceI dnaSeq : dna.getSequences())
+ {
+ for (AlignedCodonFrame mapping : mappings)
+ {
+ SequenceI prot = mapping.findAlignedSequence(dnaSeq, protein);
+ if (prot != null)
+ {
+ Mapping seqMap = mapping.getMappingForSequence(dnaSeq);
+ addCodonPositions(dnaSeq, prot, protein.getGapCharacter(),
+ seqMap, alignedCodons);
+ unmappedProtein.remove(prot);
+ }
+ }
+ }
+
+ /*
+ * Finally add any unmapped peptide start residues (e.g. for incomplete
+ * codons) as if at the codon position before the second residue
+ */
+ // TODO resolve JAL-2022 so this fudge can be removed
+ 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<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons,
+ int mappedSequenceCount)
+ {
+ // TODO delete this ugly hack once JAL-2022 is resolved
+ // i.e. we can model startPhase > 0 (incomplete start codon)
+
+ List<SequenceI> sequencesChecked = new ArrayList<SequenceI>();
+ AlignedCodon lastCodon = null;
+ Map<SequenceI, AlignedCodon> toAdd = new HashMap<SequenceI, AlignedCodon>();
+
+ for (Entry<AlignedCodon, Map<SequenceI, AlignedCodon>> entry : alignedCodons
+ .entrySet())
+ {
+ for (Entry<SequenceI, AlignedCodon> 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<SequenceI, AlignedCodon> startCodon : toAdd.entrySet())
+ {
+ addCodonToMap(alignedCodons, startCodon.getValue(),
+ startCodon.getKey());
+ }
+ }
+
+ /**
+ * 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<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons,
+ List<SequenceI> 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<SequenceI, AlignedCodon> columnResidues = alignedCodons
+ .get(codon);
+ for (Entry<SequenceI, AlignedCodon> entry : columnResidues.entrySet())
+ {
+ // place translated codon at its column position in sequence
+ entry.getKey().getSequence()[column] = entry.getValue().product
+ .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<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons)
+ {
+ Iterator<AlignedCodon> 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())
+ {
+ try
+ {
+ AlignedCodon codon = codons.next();
+ addCodonToMap(alignedCodons, codon, protein);
+ } catch (IncompleteCodonException e)
+ {
+ // possible incomplete trailing codon - ignore
+ } catch (NoSuchElementException e)
+ {
+ // possibly peptide lacking STOP
+ }
+ }
+ }
+
+ /**
+ * 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<AlignedCodon, Map<SequenceI, AlignedCodon>> alignedCodons,
+ AlignedCodon codon, SequenceI protein)
+ {
+ Map<SequenceI, AlignedCodon> seqProduct = alignedCodons.get(codon);
+ if (seqProduct == null)
+ {
+ seqProduct = new HashMap<SequenceI, AlignedCodon>();
+ 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:
+ * <ul>
+ * <li>One alignment must be nucleotide, and the other protein</li>
+ * <li>At least one pair of sequences must be already mapped, or mappable</li>
+ * <li>Mappable means the nucleotide translation matches the protein sequence</li>
+ * <li>The translation may ignore start and stop codons if present in the
+ * nucleotide</li>
+ * </ul>
+ *
+ * @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;
+ List<AlignedCodonFrame> 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, List<AlignedCodonFrame> mappings)
+ {
+ if (dnaSeq == null || proteinSeq == null)
+ {
+ return false;
+ }
+
+ SequenceI dnaDs = dnaSeq.getDatasetSequence() == null ? dnaSeq : dnaSeq
+ .getDatasetSequence();
+ SequenceI proteinDs = proteinSeq.getDatasetSequence() == null ? proteinSeq
+ : proteinSeq.getDatasetSequence();
+
+ for (AlignedCodonFrame mapping : mappings)
+ {
+ if (proteinDs == mapping.getAaForDnaSeq(dnaDs))
+ {
+ /*
+ * already mapped
+ */
+ return true;
+ }
+ }
+
+ /*
+ * Just try to make a mapping (it is not yet stored), test whether
+ * successful.
+ */
+ return mapCdnaToProtein(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<SequenceI> sequenceScope,
+ Map<String, String> labelForCalcId,
+ final Map<SequenceI, List<AlignmentAnnotation>> 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, <List of annotations to add> }
+ */
+ for (SequenceI seq : sequenceScope)
+ {
+ SequenceI dataset = seq.getDatasetSequence();
+ if (dataset == null)
+ {
+ continue;
+ }
+ AlignmentAnnotation[] datasetAnnotations = dataset.getAnnotation();
+ if (datasetAnnotations == null)
+ {
+ continue;
+ }
+ final List<AlignmentAnnotation> result = new ArrayList<AlignmentAnnotation>();
+ 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<AlignmentAnnotation> 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<SequenceI, List<AlignmentAnnotation>> 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<String> types, List<SequenceI> forSequences,
+ boolean anyType, boolean doShow)
+ {
+ AlignmentAnnotation[] anns = al.getAlignmentAnnotation();
+ if (anns != null)
+ {
+ for (AlignmentAnnotation aa : anns)
+ {
+ 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.getDBRefs();
+ 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 (CDS) regions in the given
+ * nucleotide sequences, and updates mappings to match. The CDS sequences are
+ * added to the original alignment's dataset, which is shared by the new
+ * alignment. Mappings from nucleotide to CDS, and from CDS to protein, are
+ * added to the alignment dataset.
+ *
+ * @param dna
+ * 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,
+ AlignmentI dataset, SequenceI[] products)
+ {
+ if (dataset == null || dataset.getDataset() != null)
+ {
+ throw new IllegalArgumentException(
+ "IMPLEMENTATION ERROR: dataset.getDataset() must be null!");
+ }
+ List<SequenceI> foundSeqs = new ArrayList<SequenceI>();
+ List<SequenceI> cdsSeqs = new ArrayList<SequenceI>();
+ List<AlignedCodonFrame> mappings = dataset.getCodonFrames();
+ HashSet<SequenceI> productSeqs = null;
+ if (products != null)
+ {
+ productSeqs = new HashSet<SequenceI>();
+ 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<AlignedCodonFrame> seqMappings = MappingUtils
+ .findMappingsForSequence(dnaSeq, mappings);
+ for (AlignedCodonFrame mapping : seqMappings)
+ {
+ List<Mapping> mappingsFromSequence = mapping
+ .getMappingsFromSequence(dnaSeq);
+
+ for (Mapping aMapping : mappingsFromSequence)
+ {
+ 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,
+ dataset).deriveSequence();
+ // cdsSeq has a name constructed as CDS|<dbref>
+ // <dbref> will be either the accession for the coding sequence,
+ // marked in the /via/ dbref to the protein product accession
+ // or it will be the original nucleotide accession.
+ SequenceI cdsSeqDss = cdsSeq.getDatasetSequence();
+
+ 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
+ */
+ List<int[]> cdsRange = Collections.singletonList(new int[] { 1,
+ cdsSeq.getLength() });
+ 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))
+ {
+ mappings.add(cdsToProteinMapping);
+ }
+
+ propagateDBRefsToCDS(cdsSeqDss, dnaSeq.getDatasetSequence(),
+ proteinProduct, aMapping);
+ /*
+ * add another mapping from original 'from' range to CDS
+ */
+ AlignedCodonFrame dnaToCdsMapping = new AlignedCodonFrame();
+ MapList dnaToCdsMap = new MapList(mapList.getFromRanges(),
+ cdsRange, 1, 1);
+ dnaToCdsMapping.addMap(dnaSeq.getDatasetSequence(), cdsSeqDss,
+ dnaToCdsMap);
+ if (!mappings.contains(dnaToCdsMapping))
+ {
+ mappings.add(dnaToCdsMapping);
+ }
+
+ /*
+ * 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
+ */
+
+ // specific use case:
+ // Genomic contig ENSCHR:1, contains coding regions for ENSG01,
+ // ENSG02, ENSG03, with transcripts and products similarly named.
+ // cannot add distinct dbrefs mapping location on ENSCHR:1 to ENSG01
+
+ // JBPNote: ?? can't actually create an example that demonstrates we
+ // need to
+ // synthesize an xref.
+
+ for (DBRefEntry primRef : dnaDss.getPrimaryDBRefs())
+ {
+ // 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)));
+ cdsSeqDss.addDBRef(cdsCrossRef);
+
+ // 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());
+ //
+ proteinToCdsRef.setMap(new Mapping(cdsSeqDss, cdsToProteinMap
+ .getInverse()));
+ proteinProduct.addDBRef(proteinToCdsRef);
+ }
+
+ /*
+ * transfer any features on dna that overlap the CDS
+ */
+ transferFeatures(dnaSeq, cdsSeq, dnaToCdsMap, 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<AlignedCodonFrame> mappings,
+ SequenceI dnaSeq, List<AlignedCodonFrame> seqMappings,
+ Mapping aMapping)
+ {
+ /*
+ * TODO a better dna-cds-protein mapping data representation to allow easy
+ * navigation; until then this clunky looping around lists of mappings
+ */
+ 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 - CODON_LENGTH)
+ {
+ return seqDss;
+ }
+
+ /*
+ * looks like we found the dna-to-protein mapping; search for the
+ * corresponding cds-to-protein mapping
+ */
+ List<AlignedCodonFrame> mappingsToPeptide = MappingUtils
+ .findMappingsForSequence(proteinProduct, mappings);
+ for (AlignedCodonFrame acf : mappingsToPeptide)
+ {
+ for (SequenceToSequenceMapping map : acf.getMappings())
+ {
+ Mapping mapping = map.getMapping();
+ if (mapping != aMapping
+ && mapping.getMap().getFromRatio() == CODON_LENGTH
+ && 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<AlignedCodonFrame> dnaToCdsMaps = MappingUtils
+ .findMappingsForSequence(cdsSeq, seqMappings);
+ if (!dnaToCdsMaps.isEmpty())
+ {
+ return cdsSeq;
+ }
+ }
+ }
+ }
+ }
+ return null;
+ }
+
+ /**
+ * Helper method that makes a CDS sequence as defined by the mappings from the
+ * given sequence i.e. extracts the 'mapped from' ranges (which may be on
+ * forward or reverse strand).
+ *
+ * @param seq
+ * @param mapping
+ * @param dataset
+ * - existing dataset. We check for sequences that look like the CDS
+ * we are about to construct, if one exists already, then we will
+ * just return that one.
+ * @return CDS sequence (as a dataset sequence)
+ */
+ static SequenceI makeCdsSequence(SequenceI seq, Mapping mapping,
+ AlignmentI dataset)
+ {
+ char[] seqChars = seq.getSequence();
+ List<int[]> fromRanges = mapping.getMap().getFromRanges();
+ int cdsWidth = MappingUtils.getLength(fromRanges);
+ char[] newSeqChars = new char[cdsWidth];
+
+ int newPos = 0;
+ for (int[] range : fromRanges)
+ {
+ if (range[0] <= range[1])
+ {
+ // forward strand mapping - just copy the range
+ int length = range[1] - range[0] + 1;
+ System.arraycopy(seqChars, range[0] - 1, newSeqChars, newPos,
+ length);
+ newPos += length;
+ }
+ else
+ {
+ // reverse strand mapping - copy and complement one by one
+ for (int i = range[0]; i >= range[1]; i--)
+ {
+ newSeqChars[newPos++] = Dna.getComplement(seqChars[i - 1]);
+ }
+ }
+ }
+
+ /*
+ * 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());
+ if (matches != null)
+ {
+ boolean matched = false;
+ for (SequenceI mtch : matches)
+ {
+ if (mtch.getStart() != newSeq.getStart())
+ {
+ continue;
+ }
+ if (mtch.getEnd() != newSeq.getEnd())
+ {
+ continue;
+ }
+ if (!Arrays.equals(mtch.getSequence(), newSeq.getSequence()))
+ {
+ continue;
+ }
+ if (!matched)
+ {
+ matched = true;
+ newSeq = mtch;
+ }
+ else
+ {
+ System.err
+ .println("JAL-2154 regression: warning - found (and ignnored a duplicate CDS sequence):"
+ + mtch.toString());
+ }
+ }
+ }
+ }
+ // newSeq.setDescription(mapFromId);
+
+ return newSeq;
+ }
+
+ /**
+ * add any DBRefEntrys to cdsSeq from contig that have a Mapping congruent to
+ * the given mapping.
+ *
+ * @param cdsSeq
+ * @param contig
+ * @param mapping
+ * @return list of DBRefEntrys added.
+ */
+ public static List<DBRefEntry> propagateDBRefsToCDS(SequenceI cdsSeq,
+ SequenceI contig, SequenceI proteinProduct, Mapping mapping)
+ {
+
+ // gather direct refs from contig congrent with mapping
+ List<DBRefEntry> direct = new ArrayList<DBRefEntry>();
+ HashSet<String> directSources = new HashSet<String>();
+ if (contig.getDBRefs() != null)
+ {
+ for (DBRefEntry dbr : contig.getDBRefs())
+ {
+ if (dbr.hasMap() && dbr.getMap().getMap().isTripletMap())
+ {
+ MapList map = dbr.getMap().getMap();
+ // check if map is the CDS mapping
+ if (mapping.getMap().equals(map))
+ {
+ direct.add(dbr);
+ directSources.add(dbr.getSource());
+ }
+ }
+ }
+ }
+ DBRefEntry[] onSource = DBRefUtils.selectRefs(
+ proteinProduct.getDBRefs(),
+ directSources.toArray(new String[0]));
+ List<DBRefEntry> propagated = new ArrayList<DBRefEntry>();
+
+ // and generate appropriate mappings
+ for (DBRefEntry cdsref : direct)
+ {
+ // 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());
+
+ // create dbref
+ DBRefEntry newref = new DBRefEntry(cdsref.getSource(),
+ cdsref.getVersion(), cdsref.getAccessionId(), new Mapping(
+ cdsmap.getTo(), cdsposmap));
+
+ // and see if we can map to the protein product for this mapping.
+ // onSource is the filtered set of accessions on protein that we are
+ // tranferring, so we assume accession is the same.
+ if (cdsmap.getTo() == null && onSource != null)
+ {
+ List<DBRefEntry> sourceRefs = DBRefUtils.searchRefs(onSource,
+ cdsref.getAccessionId());
+ if (sourceRefs != null)
+ {
+ for (DBRefEntry srcref : sourceRefs)
+ {
+ if (srcref.getSource().equalsIgnoreCase(cdsref.getSource()))
+ {
+ // we have found a complementary dbref on the protein product, so
+ // update mapping's getTo
+ newref.getMap().setTo(proteinProduct);
+ }
+ }
+ }
+ }
+ cdsSeq.addDBRef(newref);
+ propagated.add(newref);
+ }
+ return propagated;
+ }
+
+ /**
+ * 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
+ */
+ public static int transferFeatures(SequenceI fromSeq, SequenceI toSeq,
+ MapList mapping, String select, String... omitting)
+ {
+ SequenceI copyTo = toSeq;
+ while (copyTo.getDatasetSequence() != null)
+ {
+ 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)
+ {
+ if (type.equals(toOmit))
+ {
+ omit = true;
+ }
+ }
+ if (omit)
+ {
+ continue;
+ }
+
+ /*
+ * locate the mapped range - null if either start or end is
+ * not mapped (no partial overlaps are calculated)
+ */
+ 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;
+ }
+
+ /**
+ * 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<int[]> 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<int[]> proteinRange = new ArrayList<int[]>();
+
+ /*
+ * dna length should map to protein (or protein plus stop codon)
+ */
+ int codesForResidues = mappedDnaLength / CODON_LENGTH;
+ 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, CODON_LENGTH, 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). 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.
+ *
+ * @param dnaSeq
+ * @return
+ */
+ public static List<int[]> findCdsPositions(SequenceI dnaSeq)
+ {
+ List<int[]> result = new ArrayList<int[]>();
+ SequenceFeature[] sfs = dnaSeq.getSequenceFeatures();
+ if (sfs == null)
+ {
+ return result;
+ }
+
+ SequenceOntologyI so = SequenceOntologyFactory.getInstance();
+ int startPhase = 0;
+
+ for (SequenceFeature sf : sfs)
+ {
+ /*
+ * process a CDS feature (or a sub-type of CDS)
+ */
+ if (so.isA(sf.getType(), SequenceOntologyI.CDS))
+ {
+ int phase = 0;
+ try
+ {
+ phase = Integer.parseInt(sf.getPhase());
+ } catch (NumberFormatException e)
+ {
+ // ignore
+ }
+ /*
+ * phase > 0 on first codon means 5' incomplete - skip to the start
+ * of the next codon; example ENST00000496384
+ */
+ int begin = sf.getBegin();
+ int end = sf.getEnd();
+ if (result.isEmpty())
+ {
+ begin += phase;
+ if (begin > end)
+ {
+ // shouldn't happen!
+ System.err
+ .println("Error: start phase extends beyond start CDS in "
+ + dnaSeq.getName());
+ }
+ }
+ result.add(new int[] { begin, end });
+ }
+ }
+
+ /*
+ * 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
+ * ranges are assembled in order. Other cases should not use this method,
+ * but instead construct an explicit mapping for CDS (e.g. EMBL parsing).
+ */
+ Collections.sort(result, new Comparator<int[]>()
+ {
+ @Override
+ public int compare(int[] o1, int[] o2)
+ {
+ return Integer.compare(o1[0], o2[0]);
+ }
+ });
+ 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);
+
+ /*
+ * 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<Integer, List<DnaVariant>[]> variants = buildDnaVariantsMap(
+ dnaSeq, dnaToProtein);
+
+ /*
+ * scan codon variations, compute peptide variants and add to peptide sequence
+ */
+ int count = 0;
+ for (Entry<Integer, List<DnaVariant>[]> variant : variants.entrySet())
+ {
+ int peptidePos = variant.getKey();
+ List<DnaVariant>[] codonVariants = variant.getValue();
+ count += computePeptideVariants(peptide, peptidePos, codonVariants);
+ }
+
+ /*
+ * sort to get sequence features in start position order
+ * - would be better to store in Sequence as a TreeSet or NCList?
+ */
+ if (peptide.getSequenceFeatures() != null)
+ {
+ Arrays.sort(peptide.getSequenceFeatures(),
+ new Comparator<SequenceFeature>()
+ {
+ @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;
+ }
+
+ /**
+ * 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<DnaVariant>[] 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;
+ // set score to 0f so 'graduated colour' option is offered! JAL-2060
+ SequenceFeature sf = new SequenceFeature(
+ SequenceOntologyI.SEQUENCE_VARIANT, desc, peptidePos,
+ peptidePos, 0f, 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<Integer, List<DnaVariant>[]> 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<Integer, List<DnaVariant>[]> variants = new LinkedHashMap<Integer, List<DnaVariant>[]>();
+ 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];
+ List<DnaVariant>[] codonVariants = variants.get(peptidePosition);
+ if (codonVariants == null)
+ {
+ codonVariants = new ArrayList[CODON_LENGTH];
+ codonVariants[0] = new ArrayList<DnaVariant>();
+ codonVariants[1] = new ArrayList<DnaVariant>();
+ codonVariants[2] = new ArrayList<DnaVariant>();
+ 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<DnaVariant> 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.
+ *
+ * @param seqs
+ * @param xrefs
+ * @param dataset
+ * the alignment dataset shared by the new copy
+ * @return
+ */
+ public static AlignmentI makeCopyAlignment(SequenceI[] seqs,
+ SequenceI[] xrefs, AlignmentI dataset)
+ {
+ AlignmentI copy = new Alignment(new Alignment(seqs));
+ copy.setDataset(dataset);
+ boolean isProtein = !copy.isNucleotide();
+ SequenceIdMatcher matcher = new SequenceIdMatcher(seqs);
+ if (xrefs != null)
+ {
+ for (SequenceI xref : xrefs)
+ {
+ DBRefEntry[] dbrefs = xref.getDBRefs();
+ if (dbrefs != null)
+ {
+ for (DBRefEntry dbref : dbrefs)
+ {
+ if (dbref.getMap() == null || dbref.getMap().getTo() == null
+ || dbref.getMap().getTo().isProtein() != isProtein)
+ {
+ continue;
+ }
+ SequenceI mappedTo = dbref.getMap().getTo();
+ SequenceI match = matcher.findIdMatch(mappedTo);
+ if (match == null)
+ {
+ matcher.add(mappedTo);
+ copy.addSequence(mappedTo);
+ }
+ }
+ }
+ }
+ }
+ return copy;
+ }
+
+ /**
+ * Try to align sequences in 'unaligned' to match the alignment of their
+ * mapped regions in 'aligned'. For example, could use this to align CDS
+ * sequences which are mapped to their parent cDNA sequences.
+ *
+ * This method handles 1:1 mappings (dna-to-dna or protein-to-protein). For
+ * dna-to-protein or protein-to-dna use alternative methods.
+ *
+ * @param unaligned
+ * sequences to be aligned
+ * @param aligned
+ * holds aligned sequences and their mappings
+ * @return
+ */
+ 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<SequenceI> unmapped = new ArrayList<SequenceI>();
+ Map<Integer, Map<SequenceI, Character>> columnMap = buildMappedColumnsMap(
+ unaligned, aligned, unmapped);
+ int width = columnMap.size();
+ char gap = unaligned.getGapCharacter();
+ int realignedCount = 0;
+ // TODO: verify this loop scales sensibly for very wide/high alignments
+
+ for (SequenceI seq : unaligned.getSequences())
+ {
+ if (!unmapped.contains(seq))
+ {
+ char[] newSeq = new char[width];
+ Arrays.fill(newSeq, gap); // JBPComment - doubt this is faster than the
+ // Integer iteration below
+ int newCol = 0;
+ int lastCol = 0;
+
+ /*
+ * traverse the map to find columns populated
+ * by our sequence
+ */
+ for (Integer column : columnMap.keySet())
+ {
+ Character c = columnMap.get(column).get(seq);
+ if (c != null)
+ {
+ /*
+ * sequence has a character at this position
+ *
+ */
+ newSeq[newCol] = c;
+ lastCol = newCol;
+ }
+ newCol++;
+ }
+
+ /*
+ * trim trailing gaps
+ */
+ if (lastCol < width)
+ {
+ char[] tmp = new char[lastCol + 1];
+ System.arraycopy(newSeq, 0, tmp, 0, lastCol + 1);
+ newSeq = tmp;
+ }
+ // TODO: optimise SequenceI to avoid char[]->String->char[]
+ seq.setSequence(String.valueOf(newSeq));
+ realignedCount++;
+ }
+ }
+ return realignedCount;
+ }
+
+ /**
+ * 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
+ * - sequences to be aligned based on aligned
+ * @param aligned
+ * - 'guide' alignment containing sequences derived from same dataset
+ * as unaligned
+ * @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 from dataset sequence to alignment sequence(s)
+ Map<SequenceI, List<SequenceI>> alignedDatasets = new HashMap<SequenceI, List<SequenceI>>();
+ for (SequenceI seq : aligned.getSequences())
+ {
+ SequenceI ds = seq.getDatasetSequence();
+ if (alignedDatasets.get(ds) == null)
+ {
+ alignedDatasets.put(ds, new ArrayList<SequenceI>());
+ }
+ alignedDatasets.get(ds).add(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;
+ * heuristic rule: pair off sequences in order for the case where
+ * more than one shares the same dataset sequence
+ */
+ for (SequenceI seq : unaligned.getSequences())
+ {
+ List<SequenceI> 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.size() > 0)
+ {
+ // pop off aligned sequences (except the last one)
+ alignedSequences.remove(0);
+ }
+ }
+
+ 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.
+ *
+ * @param unaligned
+ * @param aligned
+ * @param unmapped
+ * @return
+ */
+ static Map<Integer, Map<SequenceI, Character>> buildMappedColumnsMap(
+ AlignmentI unaligned, AlignmentI aligned, List<SequenceI> unmapped)
+ {
+ /*
+ * Map will hold, for each aligned column position, a map of
+ * {unalignedSequence, characterPerSequence} at that position.
+ * TreeMap keeps the entries in ascending column order.
+ */
+ Map<Integer, Map<SequenceI, Character>> map = new TreeMap<Integer, Map<SequenceI, Character>>();
+
+ /*
+ * record any sequences that have no mapping so can't be realigned
+ */
+ unmapped.addAll(unaligned.getSequences());
+
+ List<AlignedCodonFrame> mappings = aligned.getCodonFrames();
+
+ for (SequenceI seq : unaligned.getSequences())
+ {
+ for (AlignedCodonFrame mapping : mappings)
+ {
+ SequenceI fromSeq = mapping.findAlignedSequence(seq, aligned);
+ if (fromSeq != null)
+ {
+ Mapping seqMap = mapping.getMappingBetween(fromSeq, seq);
+ if (addMappedPositions(seq, fromSeq, seqMap, map))
+ {
+ unmapped.remove(seq);
+ }
+ }
+ }
+ }
+ return map;
+ }
+
+ /**
+ * Helper method that adds to a map the mapped column positions of a sequence. <br>
+ * For example if aaTT-Tg-gAAA is mapped to TTTAAA then the map should record
+ * that columns 3,4,6,10,11,12 map to characters T,T,T,A,A,A of the mapped to
+ * sequence.
+ *
+ * @param seq
+ * the sequence whose column positions we are recording
+ * @param fromSeq
+ * a sequence that is mapped to the first sequence
+ * @param seqMap
+ * the mapping from 'fromSeq' to 'seq'
+ * @param map
+ * a map to add the column positions (in fromSeq) of the mapped
+ * positions of seq
+ * @return
+ */
+ static boolean addMappedPositions(SequenceI seq, SequenceI fromSeq,
+ Mapping seqMap, Map<Integer, Map<SequenceI, Character>> map)
+ {
+ if (seqMap == null)
+ {
+ 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();
+
+ /*
+ * traverse [start, end, start, end...] ranges in fromSeq
+ */
+ for (int[] fromRange : seqMap.getMap().getFromRanges())
+ {
+ for (int i = 0; i < fromRange.length - 1; i += 2)
+ {
+ boolean forward = fromRange[i + 1] >= fromRange[i];
+
+ /*
+ * find the range mapped to (sequence positions base 1)
+ */
+ int[] range = seqMap.locateMappedRange(fromRange[i],
+ fromRange[i + 1]);
+ if (range == null)
+ {
+ System.err.println("Error in mapping " + seqMap + " from "
+ + fromSeq.getName());
+ return false;
+ }
+ int fromCol = fromSeq.findIndex(fromRange[i]);
+ int mappedCharPos = range[0];
+
+ /*
+ * walk over the 'from' aligned sequence in forward or reverse
+ * direction; when a non-gap is found, record the column position
+ * of the next character of the mapped-to sequence; stop when all
+ * the characters of the range have been counted
+ */
+ while (mappedCharPos <= range[1] && fromCol <= fromChars.length
+ && fromCol >= 0)
+ {
+ if (!Comparison.isGap(fromChars[fromCol - 1]))
+ {
+ /*
+ * mapped from sequence has a character in this column
+ * record the column position for the mapped to character
+ */
+ Map<SequenceI, Character> seqsMap = map.get(fromCol);
+ if (seqsMap == null)
+ {
+ seqsMap = new HashMap<SequenceI, Character>();
+ map.put(fromCol, seqsMap);
+ }
+ seqsMap.put(seq, toChars[mappedCharPos - toStart]);
+ mappedCharPos++;
+ }
+ fromCol += (forward ? 1 : -1);
+ }
+ }
+ }
+ return true;
+ }
+
+ // strictly temporary hack until proper criteria for aligning protein to cds
+ // are in place; this is so Ensembl -> fetch xrefs Uniprot aligns the Uniprot
+ public static boolean looksLikeEnsembl(AlignmentI alignment)
+ {
+ for (SequenceI seq : alignment.getSequences())
+ {
+ String name = seq.getName();
+ if (!name.startsWith("ENSG") && !name.startsWith("ENST"))
+ {
+ return false;
+ }
+ }
+ return true;
+ }
}
git://source.jalview.org / jalview.git / blobdiff