private static VariantSample[] createVariants(
final Variant original,
final int leftClip,
final int rightClip,
Description newDescription,
int[] alleleMapping) {
final VariantSample[] newSamples = new VariantSample[original.getNumberOfSamples()];
for (int k = 0; k < newSamples.length; k++) {
final VariantSample sample = original.getSample(k);
if (sample != null) {
final String newName = createVariantName(leftClip, rightClip, sample.getName());
newSamples[k] =
new VariantSample(
sample.getPloidy(),
newName,
sample.isIdentity(),
sample.getMeasure(),
sample.isDeNovo(),
sample.getDeNovoPosterior());
VariantSample.copy(sample, newSamples[k]);
// Update counts to correspond to the new description
final Description d =
newSamples[k].getStats().counts().getDescription() instanceof DescriptionNone
? DescriptionNone.SINGLETON
: newDescription;
newSamples[k].setStats((Statistics<?>) newSamples[k].getStats().copy());
newSamples[k].getStats().remapAlleleStatistics(d, alleleMapping);
final Map<Set<String>, Double> newMap = newGenotypeLikelihoods(leftClip, rightClip, sample);
newSamples[k].setGenotypeLikelihoods(newMap);
} else {
newSamples[k] = null;
}
}
return newSamples;
}
// Can't use Description, as that includes hypotheses that weren't necessarily called.
private static HashSet<String> extractCalledAlleles(final Variant variant) {
final HashSet<String> alleles = new HashSet<>();
for (int k = 0; k < variant.getNumberOfSamples(); k++) {
final VariantSample vs = variant.getSample(k);
if (vs != null) {
if (!vs.isIdentity()) {
Collections.addAll(alleles, StringUtils.split(vs.getName(), VariantUtils.COLON));
}
}
}
return alleles;
}
private static VariantLocus createLocus(
final Variant original, final int leftClip, final int rightClip) {
final VariantLocus locus = original.getLocus();
final char newPrevNt =
leftClip == 0 ? locus.getPreviousRefNt() : locus.getRefNts().charAt(leftClip - 1);
final String newReference = StringUtils.clip(locus.getRefNts(), leftClip, rightClip);
final int newStart = locus.getStart() + leftClip;
final int newEnd = locus.getEnd() - rightClip;
return new VariantLocus(locus.getSequenceName(), newStart, newEnd, newReference, newPrevNt);
}
private static Variant createSplitVariant(
final Variant original, final int start, final int end, final int id) {
final VariantLocus newLocus = createLocus(original, start, end);
final VariantSample[] newSamples;
if (original.getNumberOfSamples() > 0) {
// trim description
Description oldDescription = DescriptionNone.SINGLETON;
for (int i = 0; i < original.getNumberOfSamples(); i++) {
if (original.getSample(i) != null
&& !(original.getSample(i).getStats().counts().getDescription()
instanceof DescriptionNone)) {
oldDescription = original.getSample(i).getStats().counts().getDescription();
}
}
// Incrementally build up mapping of old alleles to new alleles
final LinkedHashMap<String, Integer> alleles = new LinkedHashMap<>();
final int[] alleleMap = new int[oldDescription.size()];
for (int i = 0; i < oldDescription.size(); i++) {
final String clipped = StringUtils.clip(oldDescription.name(i), start, end);
Integer newPos = alleles.get(clipped);
if (newPos == null) {
newPos = alleles.size();
}
alleles.put(clipped, newPos);
alleleMap[i] = newPos;
}
final Description newDescription =
new DescriptionCommon(alleles.keySet().toArray(new String[alleles.size()]));
newSamples = createVariants(original, start, end, newDescription, alleleMap);
} else {
newSamples = new VariantSample[0];
}
final Variant result = new Variant(newLocus, newSamples);
Variant.copy(original, result);
result.setPossibleCause(createVariantName(start, end, original.getPossibleCause()));
result.setSplitId(id);
return result;
}
/**
* changes the de novo flag from true to false on any sample incorrectly marked as de novo. (note
* does not do the opposite) Also deals with the somatic cause. Some variants after splitting will
* no longer have a somatic cause.
*
* @param variant the variant to check
* @param checker the de novo checker for the current inheritance scenario
* @return the corrected variant
*/
public static Variant denovoCorrect(DenovoChecker checker, Variant variant) {
final Set<Integer> nonDenovoSamples = new HashSet<>();
for (int s = 0; s < variant.getNumberOfSamples(); s++) {
final VariantSample sample = variant.getSample(s);
if (sample != null) {
final VariantSample.DeNovoStatus denovoCall = sample.isDeNovo();
if (denovoCall == VariantSample.DeNovoStatus.IS_DE_NOVO) {
if (!checker.isDenovo(variant, s)) {
nonDenovoSamples.add(s);
}
}
}
}
final Variant ret;
if (nonDenovoSamples.size() == 0) {
ret = variant;
} else {
final VariantLocus newLocus = variant.getLocus();
final VariantSample[] newSamples = new VariantSample[variant.getNumberOfSamples()];
for (int k = 0; k < newSamples.length; k++) {
final VariantSample sample = variant.getSample(k);
if (sample != null) {
final VariantSample.DeNovoStatus newStatus;
if (sample.isDeNovo() == VariantSample.DeNovoStatus.UNSPECIFIED) {
newStatus = VariantSample.DeNovoStatus.UNSPECIFIED;
} else {
newStatus =
sample.isDeNovo() == VariantSample.DeNovoStatus.IS_DE_NOVO
&& !nonDenovoSamples.contains(k)
? VariantSample.DeNovoStatus.IS_DE_NOVO
: VariantSample.DeNovoStatus.NOT_DE_NOVO;
}
newSamples[k] =
new VariantSample(
sample.getPloidy(),
sample.getName(),
sample.isIdentity(),
sample.getMeasure(),
newStatus,
sample.getDeNovoPosterior());
VariantSample.copy(sample, newSamples[k]);
}
}
final Variant newVariant = new Variant(newLocus, newSamples);
Variant.copy(variant, newVariant);
ret = newVariant;
}
return ret;
}
static List<Variant> split(final Variant original, DenovoChecker denovoCorrector) {
// Compute set of alleles and exit if there are none
final HashSet<String> catSet = extractCalledAlleles(original);
if (catSet.size() == 0) {
return Collections.singletonList(original);
}
final String ref = original.getLocus().getRefNts();
catSet.add(ref);
// Check all are the same length, if not we cannot split
final String[] cats = catSet.toArray(new String[catSet.size()]);
final int length = cats[0].length();
for (final String c : cats) {
if (c.length() != length) {
return Collections.singletonList(original);
}
}
// After this loop, "false" in syndrome indicates a column where all alleles agree
// and thus represents a split point.
final boolean[] syndrome = new boolean[length];
final String c = cats[0];
for (int k = 1; k < cats.length; k++) {
for (int j = 0; j < length; j++) {
syndrome[j] |= c.charAt(j) != cats[k].charAt(j);
}
}
// System.err.println(java.util.Arrays.toString(syndrome));
// Check for at least one split point
boolean hasNoSplitPoint = true;
for (final boolean s : syndrome) {
hasNoSplitPoint &= s;
}
if (hasNoSplitPoint) {
return Collections.singletonList(original);
}
// Create variants around the split points
final List<Variant> list = new ArrayList<>();
int startSplit = 0;
int splitId = 0; // Unique identifier for each subcall
while (startSplit < length) {
if (syndrome[startSplit]) {
int endSplit = startSplit + 1;
while (endSplit < length && syndrome[endSplit]) {
endSplit++;
}
final Variant splitVariant =
createSplitVariant(original, startSplit, length - endSplit, splitId++);
final Variant variant =
denovoCorrector != null ? denovoCorrect(denovoCorrector, splitVariant) : splitVariant;
list.add(variant);
startSplit = endSplit + 1;
} else {
startSplit++;
}
}
return list;
}
/**
* Trim a variant by removing common prefix and suffix from each call and reference and adjusting
* all the position information accordingly.
*
* @param original the original call
* @return trimmed variant (possibly original if no change made)
*/
static Variant trim(final Variant original) {
final String ref = original.getLocus().getRefNts();
if (ref.length() == 0) {
// Cannot possibly trim if we are inserting, all bases are to be inserted
return original;
}
// Compute set of called alleles and exit if there are none
final HashSet<String> catSet = extractCalledAlleles(original);
if (catSet.size() == 0) {
return original;
}
// Include actual reference sequence (this will not be "")
assert ref.length() > 0;
catSet.add(ref);
// Compute maximal clip positions based on set of alleles
final String[] cats = catSet.toArray(new String[catSet.size()]);
final int rightClip = StringUtils.longestSuffix(cats);
final int leftClip = StringUtils.longestPrefix(rightClip, cats);
// final int leftClip = StringUtils.longestPrefix(cats);
// final int rightClip = StringUtils.longestSuffix(cats, leftClip);
// Quick exit if no trimming is possible
if (leftClip == 0 && rightClip == 0) {
return original;
}
// Create new locus, will be "" for case of pure insertion
final VariantLocus newLocus = createLocus(original, leftClip, rightClip);
final VariantSample[] newSamples;
if (original.getNumberOfSamples() > 0) {
// trim description
Description oldDescription = DescriptionNone.SINGLETON;
for (int i = 0; i < original.getNumberOfSamples(); i++) {
if (original.getSample(i) != null
&& !(original.getSample(i).getStats().counts().getDescription()
instanceof DescriptionNone)) {
oldDescription = original.getSample(i).getStats().counts().getDescription();
}
}
final String[] alleles = new String[oldDescription.size()];
final int[] alleleMap = new int[oldDescription.size()];
for (int i = 0; i < oldDescription.size(); i++) {
final String clipped = StringUtils.clip(oldDescription.name(i), leftClip, rightClip);
alleles[i] = clipped;
alleleMap[i] = i;
}
final Description newDescription = new DescriptionCommon(alleles);
// Create new trimmed samples
newSamples = createVariants(original, leftClip, rightClip, newDescription, alleleMap);
} else {
newSamples = new VariantSample[0];
}
// Create new variant from the new samples
final Variant result = new Variant(newLocus, newSamples);
Variant.copy(original, result);
// This must be done after the copy
result.setPossibleCause(createVariantName(leftClip, rightClip, original.getPossibleCause()));
result.setTrimmed();
// System.err.println(original);
// System.err.println(result);
return result;
}