/** Check proteins using all possible codon tables */
void checkCodonTables() {
if (verbose) Timer.showStdErr("Comparing Proteins...");
createTrByChromo(); // Create lists of transcripts by chromosome
// For each chromosome...
for (Chromosome chromo : genome) {
String chr = chromo.getId();
// Check against each codon table
for (CodonTable codonTable : CodonTables.getInstance()) {
setCodonTable(chromo, codonTable);
proteinCompare(chr, false, false);
}
}
if (verbose) Timer.showStdErr("done");
}
/** Set codon table for a given chromosome */
void setCodonTable(Chromosome chromo, CodonTable codonTable) {
CodonTables.getInstance().set(genome, chromo, codonTable); // Set codon tables
// Reset all protein translations for this chromosome
for (Transcript tr : trByChromo.get(chromo.getId())) tr.resetCache();
}
/** Create a variant */
List<Variant> variants(Chromosome chromo, int start, String reference, String alt, String id) {
List<Variant> list = null;
if (alt != null) alt = alt.toUpperCase();
if (alt == null || alt.isEmpty() || alt.equals(reference)) {
// Non-variant
list = Variant.factory(chromo, start, reference, null, id, false);
} else if (alt.charAt(0) == '<') {
// Structural variants
if (alt.startsWith("<DEL")) {
// Case: Deletion
// 2 321682 . T <DEL> 6 PASS
// IMPRECISE;SVTYPE=DEL;END=321887;SVLEN=-105;CIPOS=-56,20;CIEND=-10,62
String ch = ref;
int startNew = start;
if (end > start) {
startNew = start + reference.length();
int size = end - startNew + 1;
char change[] = new char[size];
for (int i = 0; i < change.length; i++)
change[i] = reference.length() > i ? reference.charAt(i) : 'N';
ch = new String(change);
}
list = Variant.factory(chromo, startNew, ch, "", id, false);
} else if (alt.startsWith("<INV")) {
// Inversion
int startNew = start + reference.length();
Variant var = new Variant(chromo, startNew, end, id);
var.setVariantType(VariantType.INV);
list = new LinkedList<>();
list.add(var);
} else if (alt.startsWith("<DUP")) {
// Duplication
int startNew = start + reference.length();
Variant var = new Variant(chromo, startNew, end, id);
var.setVariantType(VariantType.DUP);
list = new LinkedList<>();
list.add(var);
}
} else if ((alt.indexOf('[') >= 0) || (alt.indexOf(']') >= 0)) {
// Translocations
// Parse ALT string
boolean left = alt.indexOf(']') >= 0;
String sep = (left ? "\\]" : "\\[");
String tpos[] = alt.split(sep);
String pos = tpos[1];
boolean before = (alt.indexOf(']') == 0) || (alt.indexOf('[') == 0);
String altBases = (before ? tpos[2] : tpos[0]);
// Parse 'chr:start'
String posSplit[] = pos.split(":");
String trChrName = posSplit[0];
Chromosome trChr = chromo.getGenome().getOrCreateChromosome(trChrName);
int trStart = Gpr.parseIntSafe(posSplit[1]) - 1;
VariantBnd var = new VariantBnd(chromo, start, ref, altBases, trChr, trStart, left, before);
list = new LinkedList<>();
list.add(var);
} else if (reference.length() == alt.length()) {
// Case: SNP, MNP
if (reference.length() == 1) {
// SNPs
// 20 3 . C G . PASS DP=100
list = Variant.factory(chromo, start, reference, alt, id, true);
} else {
// MNPs
// 20 3 . TC AT . PASS DP=100
// Sometimes the first bases are the same and we can trim them
int startDiff = Integer.MAX_VALUE;
for (int i = 0; i < reference.length(); i++)
if (reference.charAt(i) != alt.charAt(i)) startDiff = Math.min(startDiff, i);
// MNPs
// Sometimes the last bases are the same and we can trim them
int endDiff = 0;
for (int i = reference.length() - 1; i >= 0; i--)
if (reference.charAt(i) != alt.charAt(i)) endDiff = Math.max(endDiff, i);
String newRef = reference.substring(startDiff, endDiff + 1);
String newAlt = alt.substring(startDiff, endDiff + 1);
list = Variant.factory(chromo, start + startDiff, newRef, newAlt, id, true);
}
} else {
// Short Insertions, Deletions or Mixed Variants (substitutions)
VcfRefAltAlign align = new VcfRefAltAlign(alt, reference);
align.align();
int startDiff = align.getOffset();
switch (align.getVariantType()) {
case DEL:
// Case: Deletion
// 20 2 . TC T . PASS DP=100
// 20 2 . AGAC AAC . PASS DP=100
String ref = "";
String ch = align.getAlignment();
if (!ch.startsWith("-"))
throw new RuntimeException(
"Deletion '" + ch + "' does not start with '-'. This should never happen!");
list = Variant.factory(chromo, start + startDiff, ref, ch, id, true);
break;
case INS:
// Case: Insertion of A { tC ; tCA } tC is the reference allele
// 20 2 . TC TCA . PASS DP=100
ch = align.getAlignment();
ref = "";
if (!ch.startsWith("+"))
throw new RuntimeException(
"Insertion '" + ch + "' does not start with '+'. This should never happen!");
list = Variant.factory(chromo, start + startDiff, ref, ch, id, true);
break;
case MIXED:
// Case: Mixed variant (substitution)
reference = reference.substring(startDiff);
alt = alt.substring(startDiff);
list = Variant.factory(chromo, start + startDiff, reference, alt, id, true);
break;
default:
// Other change type?
throw new RuntimeException(
"Unsupported VCF change type '"
+ align.getVariantType()
+ "'\n\tRef: "
+ reference
+ "'\n\tAlt: '"
+ alt
+ "'\n\tVcfEntry: "
+ this);
}
}
// ---
// Add original 'ALT' field as genotype
// ---
if (list == null) list = new LinkedList<>();
for (Variant variant : list) variant.setGenotype(alt);
return list;
}