/*
* Jalview - A Sequence Alignment Editor and Viewer ($$Version-Rel$$)
* Copyright (C) $$Year-Rel$$ The Jalview Authors
*
* This file is part of Jalview.
*
* Jalview is free software: you can redistribute it and/or
* modify it under the terms of the GNU General Public License
* as published by the Free Software Foundation, either version 3
* of the License, or (at your option) any later version.
*
* Jalview is distributed in the hope that it will be useful, but
* WITHOUT ANY WARRANTY; without even the implied warranty
* of MERCHANTABILITY or FITNESS FOR A PARTICULAR
* PURPOSE. See the GNU General Public License for more details.
*
* You should have received a copy of the GNU General Public License
* along with Jalview. If not, see .
* The Jalview Authors are detailed in the 'AUTHORS' file.
*/
package jalview.analysis;
import jalview.api.AlignViewportI;
import jalview.datamodel.AlignedCodon;
import jalview.datamodel.AlignedCodonFrame;
import jalview.datamodel.Alignment;
import jalview.datamodel.AlignmentAnnotation;
import jalview.datamodel.AlignmentI;
import jalview.datamodel.Annotation;
import jalview.datamodel.DBRefEntry;
import jalview.datamodel.DBRefSource;
import jalview.datamodel.FeatureProperties;
import jalview.datamodel.GraphLine;
import jalview.datamodel.Mapping;
import jalview.datamodel.Sequence;
import jalview.datamodel.SequenceFeature;
import jalview.datamodel.SequenceI;
import jalview.schemes.ResidueProperties;
import jalview.util.Comparison;
import jalview.util.DBRefUtils;
import jalview.util.MapList;
import jalview.util.ShiftList;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.Comparator;
import java.util.Iterator;
import java.util.List;
public class Dna
{
private static final String STOP_ASTERIX = "*";
private static final Comparator comparator = new CodonComparator();
/*
* 'final' variables describe the inputs to the translation, which should not
* be modified.
*/
private final List selection;
private final String[] seqstring;
private final Iterator contigs;
private final char gapChar;
private final AlignmentAnnotation[] annotations;
private final int dnaWidth;
private final AlignmentI dataset;
private ShiftList vismapping;
private int[] startcontigs;
/*
* Working variables for the translation.
*
* The width of the translation-in-progress protein alignment.
*/
private int aaWidth = 0;
/*
* This array will be built up so that position i holds the codon positions
* e.g. [7, 9, 10] that match column i (base 0) in the aligned translation.
* Note this implies a contract that if two codons do not align exactly, their
* translated products must occupy different column positions.
*/
private AlignedCodon[] alignedCodons;
/**
* Constructor given a viewport and the visible contigs.
*
* @param viewport
* @param visibleContigs
*/
public Dna(AlignViewportI viewport, Iterator visibleContigs)
{
this.selection = Arrays.asList(viewport.getSequenceSelection());
this.seqstring = viewport.getViewAsString(true);
this.contigs = visibleContigs;
this.gapChar = viewport.getGapCharacter();
this.annotations = viewport.getAlignment().getAlignmentAnnotation();
this.dnaWidth = viewport.getAlignment().getWidth();
this.dataset = viewport.getAlignment().getDataset();
initContigs();
}
/**
* Initialise contigs used as starting point for translateCodingRegion
*/
private void initContigs()
{
vismapping = new ShiftList(); // map from viscontigs to seqstring
// intervals
int npos = 0;
int[] lastregion = null;
ArrayList tempcontigs = new ArrayList<>();
while (contigs.hasNext())
{
int[] region = contigs.next();
if (lastregion == null)
{
vismapping.addShift(npos, region[0]);
}
else
{
// hidden region
vismapping.addShift(npos, region[0] - lastregion[1] + 1);
}
lastregion = region;
tempcontigs.add(region[0]);
tempcontigs.add(region[1]);
}
startcontigs = new int[tempcontigs.size()];
int i = 0;
for (Integer val : tempcontigs)
{
startcontigs[i] = val;
i++;
}
tempcontigs = null;
}
/**
* Test whether codon positions cdp1 should align before, with, or after cdp2.
* Returns zero if all positions match (or either argument is null). Returns
* -1 if any position in the first codon precedes the corresponding position
* in the second codon. Else returns +1 (some position in the second codon
* precedes the corresponding position in the first).
*
* Note this is not necessarily symmetric, for example:
*
* - compareCodonPos([2,5,6], [3,4,5]) returns -1
* - compareCodonPos([3,4,5], [2,5,6]) also returns -1
*
*
* @param ac1
* @param ac2
* @return
*/
public static final int compareCodonPos(AlignedCodon ac1, AlignedCodon ac2)
{
return comparator.compare(ac1, ac2);
// return jalview_2_8_2compare(ac1, ac2);
}
/**
* Codon comparison up to Jalview 2.8.2. This rule is sequence order dependent
* - see http://issues.jalview.org/browse/JAL-1635
*
* @param ac1
* @param ac2
* @return
*/
private static int jalview_2_8_2compare(AlignedCodon ac1,
AlignedCodon ac2)
{
if (ac1 == null || ac2 == null || (ac1.equals(ac2)))
{
return 0;
}
if (ac1.pos1 < ac2.pos1 || ac1.pos2 < ac2.pos2 || ac1.pos3 < ac2.pos3)
{
// one base in cdp1 precedes the corresponding base in the other codon
return -1;
}
// one base in cdp1 appears after the corresponding base in the other codon.
return 1;
}
/**
* Translates cDNA using the specified code table
*
* @return
*/
public AlignmentI translateCdna(GeneticCodeI codeTable)
{
AlignedCodonFrame acf = new AlignedCodonFrame();
alignedCodons = new AlignedCodon[dnaWidth];
int s;
int sSize = selection.size();
List pepseqs = new ArrayList<>();
for (s = 0; s < sSize; s++)
{
SequenceI newseq = translateCodingRegion(selection.get(s),
seqstring[s], acf, pepseqs, codeTable);
if (newseq != null)
{
pepseqs.add(newseq);
SequenceI ds = newseq;
if (dataset != null)
{
while (ds.getDatasetSequence() != null)
{
ds = ds.getDatasetSequence();
}
dataset.addSequence(ds);
}
}
}
SequenceI[] newseqs = pepseqs.toArray(new SequenceI[pepseqs.size()]);
AlignmentI al = new Alignment(newseqs);
// ensure we look aligned.
al.padGaps();
// link the protein translation to the DNA dataset
al.setDataset(dataset);
translateAlignedAnnotations(al, acf);
al.addCodonFrame(acf);
return al;
}
/**
* fake the collection of DbRefs with associated exon mappings to identify if
* a translation would generate distinct product in the currently selected
* region.
*
* @param selection
* @param viscontigs
* @return
*/
public static boolean canTranslate(SequenceI[] selection,
int viscontigs[])
{
for (int gd = 0; gd < selection.length; gd++)
{
SequenceI dna = selection[gd];
List dnarefs = DBRefUtils.selectRefs(dna.getDBRefs(),
jalview.datamodel.DBRefSource.DNACODINGDBS);
if (dnarefs != null)
{
// intersect with pep
List mappedrefs = new ArrayList<>();
List refs = dna.getDBRefs();
for (int d = 0, nd = refs.size(); d < nd; d++)
{
DBRefEntry ref = refs.get(d);
if (ref.getMap() != null && ref.getMap().getMap() != null
&& ref.getMap().getMap().getFromRatio() == 3
&& ref.getMap().getMap().getToRatio() == 1)
{
mappedrefs.add(ref); // add translated protein maps
}
}
dnarefs = mappedrefs;//.toArray(new DBRefEntry[mappedrefs.size()]);
for (int d = 0, nd = dnarefs.size(); d < nd; d++)
{
Mapping mp = dnarefs.get(d).getMap();
if (mp != null)
{
for (int vc = 0, nv = viscontigs.length; vc < nv; vc += 2)
{
int[] mpr = mp.locateMappedRange(viscontigs[vc],
viscontigs[vc + 1]);
if (mpr != null)
{
return true;
}
}
}
}
}
}
return false;
}
/**
* Translate nucleotide alignment annotations onto translated amino acid
* alignment using codon mapping codons
*
* @param al
* the translated protein alignment
*/
protected void translateAlignedAnnotations(AlignmentI al,
AlignedCodonFrame acf)
{
// Can only do this for columns with consecutive codons, or where
// annotation is sequence associated.
if (annotations != null)
{
for (AlignmentAnnotation annotation : annotations)
{
/*
* Skip hidden or autogenerated annotation. Also (for now), RNA
* secondary structure annotation. If we want to show this against
* protein we need a smarter way to 'translate' without generating
* invalid (unbalanced) structure annotation.
*/
if (annotation.autoCalculated || !annotation.visible
|| annotation.isRNA())
{
continue;
}
int aSize = aaWidth;
Annotation[] anots = (annotation.annotations == null) ? null
: new Annotation[aSize];
if (anots != null)
{
for (int a = 0; a < aSize; a++)
{
// process through codon map.
if (a < alignedCodons.length && alignedCodons[a] != null
&& alignedCodons[a].pos1 == (alignedCodons[a].pos3 - 2))
{
anots[a] = getCodonAnnotation(alignedCodons[a],
annotation.annotations);
}
}
}
AlignmentAnnotation aa = new AlignmentAnnotation(annotation.label,
annotation.description, anots);
aa.graph = annotation.graph;
aa.graphGroup = annotation.graphGroup;
aa.graphHeight = annotation.graphHeight;
if (annotation.getThreshold() != null)
{
aa.setThreshold(new GraphLine(annotation.getThreshold()));
}
if (annotation.hasScore)
{
aa.setScore(annotation.getScore());
}
final SequenceI seqRef = annotation.sequenceRef;
if (seqRef != null)
{
SequenceI aaSeq = acf.getAaForDnaSeq(seqRef);
if (aaSeq != null)
{
// aa.compactAnnotationArray(); // throw away alignment annotation
// positioning
aa.setSequenceRef(aaSeq);
// rebuild mapping
aa.createSequenceMapping(aaSeq, aaSeq.getStart(), true);
aa.adjustForAlignment();
aaSeq.addAlignmentAnnotation(aa);
}
}
al.addAnnotation(aa);
}
}
}
private static Annotation getCodonAnnotation(AlignedCodon is,
Annotation[] annotations)
{
// Have a look at all the codon positions for annotation and put the first
// one found into the translated annotation pos.
int contrib = 0;
Annotation annot = null;
for (int p = 1; p <= 3; p++)
{
int dnaCol = is.getBaseColumn(p);
if (annotations[dnaCol] != null)
{
if (annot == null)
{
annot = new Annotation(annotations[dnaCol]);
contrib = 1;
}
else
{
// merge with last
Annotation cpy = new Annotation(annotations[dnaCol]);
if (annot.colour == null)
{
annot.colour = cpy.colour;
}
if (annot.description == null || annot.description.length() == 0)
{
annot.description = cpy.description;
}
if (annot.displayCharacter == null)
{
annot.displayCharacter = cpy.displayCharacter;
}
if (annot.secondaryStructure == 0)
{
annot.secondaryStructure = cpy.secondaryStructure;
}
annot.value += cpy.value;
contrib++;
}
}
}
if (contrib > 1)
{
annot.value /= contrib;
}
return annot;
}
/**
* Translate a na sequence
*
* @param selection
* sequence displayed under viscontigs visible columns
* @param seqstring
* ORF read in some global alignment reference frame
* @param acf
* Definition of global ORF alignment reference frame
* @param proteinSeqs
* @param codeTable
* @return sequence ready to be added to alignment.
*/
protected SequenceI translateCodingRegion(SequenceI selection,
String seqstring, AlignedCodonFrame acf,
List proteinSeqs, GeneticCodeI codeTable)
{
List skip = new ArrayList<>();
int[] skipint = null;
int npos = 0;
int vc = 0;
int[] scontigs = new int[startcontigs.length];
System.arraycopy(startcontigs, 0, scontigs, 0, startcontigs.length);
// allocate a roughly sized buffer for the protein sequence
StringBuilder protein = new StringBuilder(seqstring.length() / 2);
String seq = seqstring.replace('U', 'T').replace('u', 'T');
char codon[] = new char[3];
int cdp[] = new int[3];
int rf = 0;
int lastnpos = 0;
int nend;
int aspos = 0;
int resSize = 0;
for (npos = 0, nend = seq.length(); npos < nend; npos++)
{
if (!Comparison.isGap(seq.charAt(npos)))
{
cdp[rf] = npos; // store position
codon[rf++] = seq.charAt(npos); // store base
}
if (rf == 3)
{
/*
* Filled up a reading frame...
*/
AlignedCodon alignedCodon = new AlignedCodon(cdp[0], cdp[1], cdp[2]);
String aa = codeTable.translate(new String(codon));
rf = 0;
final String gapString = String.valueOf(gapChar);
if (aa == null)
{
aa = gapString;
if (skipint == null)
{
skipint = new int[] { alignedCodon.pos1,
alignedCodon.pos3 /*
* cdp[0],
* cdp[2]
*/ };
}
skipint[1] = alignedCodon.pos3; // cdp[2];
}
else
{
if (skipint != null)
{
// edit scontigs
skipint[0] = vismapping.shift(skipint[0]);
skipint[1] = vismapping.shift(skipint[1]);
for (vc = 0; vc < scontigs.length;)
{
if (scontigs[vc + 1] < skipint[0])
{
// before skipint starts
vc += 2;
continue;
}
if (scontigs[vc] > skipint[1])
{
// finished editing so
break;
}
// Edit the contig list to include the skipped region which did
// not translate
int[] t;
// from : s1 e1 s2 e2 s3 e3
// to s: s1 e1 s2 k0 k1 e2 s3 e3
// list increases by one unless one boundary (s2==k0 or e2==k1)
// matches, and decreases by one if skipint intersects whole
// visible contig
if (scontigs[vc] <= skipint[0])
{
if (skipint[0] == scontigs[vc])
{
// skipint at start of contig
// shift the start of this contig
if (scontigs[vc + 1] > skipint[1])
{
scontigs[vc] = skipint[1];
vc += 2;
}
else
{
if (scontigs[vc + 1] == skipint[1])
{
// remove the contig
t = new int[scontigs.length - 2];
if (vc > 0)
{
System.arraycopy(scontigs, 0, t, 0, vc - 1);
}
if (vc + 2 < t.length)
{
System.arraycopy(scontigs, vc + 2, t, vc,
t.length - vc + 2);
}
scontigs = t;
}
else
{
// truncate contig to before the skipint region
scontigs[vc + 1] = skipint[0] - 1;
vc += 2;
}
}
}
else
{
// scontig starts before start of skipint
if (scontigs[vc + 1] < skipint[1])
{
// skipint truncates end of scontig
scontigs[vc + 1] = skipint[0] - 1;
vc += 2;
}
else
{
// divide region to new contigs
t = new int[scontigs.length + 2];
System.arraycopy(scontigs, 0, t, 0, vc + 1);
t[vc + 1] = skipint[0];
t[vc + 2] = skipint[1];
System.arraycopy(scontigs, vc + 1, t, vc + 3,
scontigs.length - (vc + 1));
scontigs = t;
vc += 4;
}
}
}
}
skip.add(skipint);
skipint = null;
}
if (aa.equals(ResidueProperties.STOP))
{
aa = STOP_ASTERIX;
}
resSize++;
}
boolean findpos = true;
while (findpos)
{
/*
* Compare this codon's base positions with those currently aligned to
* this column in the translation.
*/
final int compareCodonPos = compareCodonPos(alignedCodon,
alignedCodons[aspos]);
switch (compareCodonPos)
{
case -1:
/*
* This codon should precede the mapped positions - need to insert a
* gap in all prior sequences.
*/
insertAAGap(aspos, proteinSeqs);
findpos = false;
break;
case +1:
/*
* This codon belongs after the aligned codons at aspos. Prefix it
* with a gap and try the next position.
*/
aa = gapString + aa;
aspos++;
break;
case 0:
/*
* Exact match - codon 'belongs' at this translated position.
*/
findpos = false;
}
}
protein.append(aa);
lastnpos = npos;
if (alignedCodons[aspos] == null)
{
// mark this column as aligning to this aligned reading frame
alignedCodons[aspos] = alignedCodon;
}
else if (!alignedCodons[aspos].equals(alignedCodon))
{
throw new IllegalStateException(
"Tried to coalign " + alignedCodons[aspos].toString()
+ " with " + alignedCodon.toString());
}
if (aspos >= aaWidth)
{
// update maximum alignment width
aaWidth = aspos;
}
// ready for next translated reading frame alignment position (if any)
aspos++;
}
}
if (resSize > 0)
{
SequenceI newseq = new Sequence(selection.getName(),
protein.toString());
if (rf != 0)
{
final String errMsg = "trimming contigs for incomplete terminal codon.";
System.err.println(errMsg);
// map and trim contigs to ORF region
vc = scontigs.length - 1;
lastnpos = vismapping.shift(lastnpos); // place npos in context of
// whole dna alignment (rather
// than visible contigs)
// incomplete ORF could be broken over one or two visible contig
// intervals.
while (vc >= 0 && scontigs[vc] > lastnpos)
{
if (vc > 0 && scontigs[vc - 1] > lastnpos)
{
vc -= 2;
}
else
{
// correct last interval in list.
scontigs[vc] = lastnpos;
}
}
if (vc > 0 && (vc + 1) < scontigs.length)
{
// truncate map list to just vc elements
int t[] = new int[vc + 1];
System.arraycopy(scontigs, 0, t, 0, vc + 1);
scontigs = t;
}
if (vc <= 0)
{
scontigs = null;
}
}
if (scontigs != null)
{
npos = 0;
// map scontigs to actual sequence positions on selection
for (vc = 0; vc < scontigs.length; vc += 2)
{
scontigs[vc] = selection.findPosition(scontigs[vc]); // not from 1!
scontigs[vc + 1] = selection.findPosition(scontigs[vc + 1]); // exclusive
if (scontigs[vc + 1] == selection.getEnd())
{
break;
}
}
// trim trailing empty intervals.
if ((vc + 2) < scontigs.length)
{
int t[] = new int[vc + 2];
System.arraycopy(scontigs, 0, t, 0, vc + 2);
scontigs = t;
}
/*
* delete intervals in scontigs which are not translated. 1. map skip
* into sequence position intervals 2. truncate existing ranges and add
* new ranges to exclude untranslated regions. if (skip.size()>0) {
* Vector narange = new Vector(); for (vc=0; vc=skipint[0] &&
* iv[0]<=skipint[1]) { if (iv[0]==skipint[0]) { // delete beginning of
* range } else { // truncate range and create new one if necessary iv =
* (int[]) narange.elementAt(vc+1); if (iv[0]<=skipint[1]) { // truncate
* range iv[0] = skipint[1]; } else { } } } else if (iv[0] proteinSeqs)
{
aaWidth++;
for (SequenceI seq : proteinSeqs)
{
seq.insertCharAt(pos, gapChar);
}
checkCodonFrameWidth();
if (pos < aaWidth)
{
aaWidth++;
/*
* Shift from [pos] to the end one to the right, and null out [pos]
*/
System.arraycopy(alignedCodons, pos, alignedCodons, pos + 1,
alignedCodons.length - pos - 1);
alignedCodons[pos] = null;
}
}
/**
* Check the codons array can accommodate a single insertion, if not resize
* it.
*/
protected void checkCodonFrameWidth()
{
if (alignedCodons[alignedCodons.length - 1] != null)
{
/*
* arraycopy insertion would bump a filled slot off the end, so expand.
*/
AlignedCodon[] c = new AlignedCodon[alignedCodons.length + 10];
System.arraycopy(alignedCodons, 0, c, 0, alignedCodons.length);
alignedCodons = c;
}
}
/**
* Given a peptide newly translated from a dna sequence, copy over and set any
* features on the peptide from the DNA.
*
* @param dna
* @param pep
* @param map
*/
private static void transferCodedFeatures(SequenceI dna, SequenceI pep,
MapList map)
{
// BH 2019.01.25 nop?
// List dnarefs = DBRefUtils.selectRefs(dna.getDBRefs(),
// DBRefSource.DNACODINGDBS);
// if (dnarefs != null)
// {
// // intersect with pep
// for (int d = 0, nd = dnarefs.size(); d < nd; d++)
// {
// Mapping mp = dnarefs.get(d).getMap();
// if (mp != null)
// {
// }
// }
// }
for (SequenceFeature sf : dna.getFeatures().getAllFeatures())
{
if (FeatureProperties.isCodingFeature(null, sf.getType()))
{
// if (map.intersectsFrom(sf[f].begin, sf[f].end))
{
}
}
}
}
/**
* Returns an alignment consisting of the reversed (and optionally
* complemented) sequences set in this object's constructor
*
* @param complement
* @return
*/
public AlignmentI reverseCdna(boolean complement)
{
int sSize = selection.size();
List reversed = new ArrayList<>();
for (int s = 0; s < sSize; s++)
{
SequenceI newseq = reverseSequence(selection.get(s).getName(),
seqstring[s], complement);
if (newseq != null)
{
reversed.add(newseq);
}
}
SequenceI[] newseqs = reversed.toArray(new SequenceI[reversed.size()]);
AlignmentI al = new Alignment(newseqs);
((Alignment) al).createDatasetAlignment();
return al;
}
/**
* Returns a reversed, and optionally complemented, sequence. The new
* sequence's name is the original name with "|rev" or "|revcomp" appended.
* aAcCgGtT and DNA ambiguity codes are complemented, any other characters are
* left unchanged.
*
* @param seq
* @param complement
* @return
*/
public static SequenceI reverseSequence(String seqName, String sequence,
boolean complement)
{
String newName = seqName + "|rev" + (complement ? "comp" : "");
char[] originalSequence = sequence.toCharArray();
int length = originalSequence.length;
char[] reversedSequence = new char[length];
int bases = 0;
for (int i = 0; i < length; i++)
{
char c = complement ? getComplement(originalSequence[i])
: originalSequence[i];
reversedSequence[length - i - 1] = c;
if (!Comparison.isGap(c))
{
bases++;
}
}
SequenceI reversed = new Sequence(newName, reversedSequence, 1, bases);
return reversed;
}
/**
* Answers the reverse complement of the input string
*
* @see #getComplement(char)
* @param s
* @return
*/
public static String reverseComplement(String s)
{
StringBuilder sb = new StringBuilder(s.length());
for (int i = s.length() - 1; i >= 0; i--)
{
sb.append(Dna.getComplement(s.charAt(i)));
}
return sb.toString();
}
/**
* Returns dna complement (preserving case) for aAcCgGtTuU. Ambiguity codes
* are treated as on http://reverse-complement.com/. Anything else is left
* unchanged.
*
* @param c
* @return
*/
public static char getComplement(char c)
{
char result = c;
switch (c)
{
case '-':
case '.':
case ' ':
break;
case 'a':
result = 't';
break;
case 'A':
result = 'T';
break;
case 'c':
result = 'g';
break;
case 'C':
result = 'G';
break;
case 'g':
result = 'c';
break;
case 'G':
result = 'C';
break;
case 't':
result = 'a';
break;
case 'T':
result = 'A';
break;
case 'u':
result = 'a';
break;
case 'U':
result = 'A';
break;
case 'r':
result = 'y';
break;
case 'R':
result = 'Y';
break;
case 'y':
result = 'r';
break;
case 'Y':
result = 'R';
break;
case 'k':
result = 'm';
break;
case 'K':
result = 'M';
break;
case 'm':
result = 'k';
break;
case 'M':
result = 'K';
break;
case 'b':
result = 'v';
break;
case 'B':
result = 'V';
break;
case 'v':
result = 'b';
break;
case 'V':
result = 'B';
break;
case 'd':
result = 'h';
break;
case 'D':
result = 'H';
break;
case 'h':
result = 'd';
break;
case 'H':
result = 'D';
break;
}
return result;
}
}