void GenomicRegionCollection<T>::CreateTreeMap() {
if (!m_grv->size())
return;
// sort the genomic intervals
if (!m_sorted)
CoordinateSort();
// loop through and make the intervals for each chromosome
GenomicIntervalMap map;
for (size_t i = 0; i < m_grv->size(); ++i) {
map[m_grv->at(i).chr].push_back(GenomicInterval(m_grv->at(i).pos1, m_grv->at(i).pos2, i));
}
// for each chr, make the tree from the intervals
//for (auto it : map) {
for (GenomicIntervalMap::iterator it = map.begin(); it != map.end(); ++it) {
GenomicIntervalTreeMap::iterator ff = m_tree->find(it->first);
if (ff != m_tree->end())
ff->second = GenomicIntervalTree(it->second);
else
m_tree->insert(std::pair<int, GenomicIntervalTree>(it->first, GenomicIntervalTree(it->second)));
//old //m_tree[it.first] = GenomicIntervalTree(it.second);
}
}
GenomicInterval parseInputInterval(string const & location) {
size_t idx = location.find(":");
if (idx == string::npos) {
cerr << "[ERROR] Can not parse the input interval. Expected format: chr2:5000000-100000000" << endl;
exit(1);
}
int chr = stoi( location.substr(0, idx).substr(3) );
size_t idx2 = location.find('-', idx);
if (idx2 == string::npos) {
cerr << "[ERROR] Can not parse the input interval. Expected format: chr2:5000000-100000000" << endl;
exit(1);
}
int start_coord = stoi( location.substr(idx+1, idx2 - idx) );
int end_coord = stoi( location.substr(idx2+1) );
cerr << chr << " " << start_coord << " " << end_coord << endl;
return GenomicInterval(chr, start_coord, end_coord);
}
int VariantMaterializer::_materializeLargeVariants(
seqan::Dna5String & seq,
MethylationLevels * levelsLargeVariants,
std::vector<SmallVarInfo> & varInfos,
std::vector<std::pair<int, int> > & breakpoints,
PositionMap & positionMap,
TJournalEntries const & journal,
seqan::Dna5String const & contig,
std::vector<SmallVarInfo> const & smallVarInfos,
Variants const & variants,
MethylationLevels const * levels,
int hId)
{
if (methSimOptions)
{
SEQAN_ASSERT_EQ(methSimOptions->simulateMethylationLevels, (levelsLargeVariants != 0));
SEQAN_ASSERT_EQ(methSimOptions->simulateMethylationLevels, (levels != 0));
}
// We will record all intervals for the positionMap.svIntervalTree in this String.
seqan::String<GenomicInterval> intervals;
// Clear output methylation levels->
if (levelsLargeVariants)
levelsLargeVariants->clear();
// Store variation points. We reuse the fixVariationLevels() function from small indel/snp simulation and thus
// have to store a bool that is always set to false.
seqan::String<std::pair<int, bool> > varPoints;
// Track last position from contig appended to seq so far.
int lastPos = 0;
if (verbosity >= 3)
std::cerr << __LINE__ << "\tlastPos == " << lastPos << "\n";
// Pointer to the current small variant to write out translated to varInfo.
std::vector<SmallVarInfo>::const_iterator itSmallVar = smallVarInfos.begin();
// Number of bytes written out so far/current position in variant.
unsigned currentPos = 0;
for (unsigned i = 0; i < length(variants.svRecords); ++i)
{
if (variants.svRecords[i].haplotype != hId) // Ignore all but the current contig.
continue;
// We obtain a copy of the current SV record since we translate its positions below.
StructuralVariantRecord svRecord = variants.svRecords[i];
// Translate positions and lengths of SV record.
if (verbosity >= 2)
std::cerr << " Translating SvRecord\n " << svRecord << '\n';
svRecord.pos = hostToVirtualPosition(journal, svRecord.pos);
SEQAN_ASSERT_LT(svRecord.pos, (int)length(contig));
// We do not need to adjust the sizes for insertions.
if (svRecord.kind != StructuralVariantRecord::INDEL || svRecord.size < 0)
svRecord.size = hostToVirtualPosition(journal, svRecord.pos + svRecord.size) -
hostToVirtualPosition(journal, svRecord.pos);
if (svRecord.targetPos != -1)
svRecord.targetPos = hostToVirtualPosition(journal, svRecord.targetPos);
if (verbosity >= 2)
std::cerr << " => " << svRecord << '\n';
// Copy out small variant infos for interim chars.
for (; itSmallVar != smallVarInfos.end() && itSmallVar->pos < svRecord.pos; ++itSmallVar)
{
int offset = (int)currentPos - lastPos;
varInfos.push_back(*itSmallVar);
varInfos.back().pos += offset;
}
// Copy from contig to seq with SVs.
if (verbosity >= 3)
std::cerr << "lastPos == " << lastPos << "\n";
append(seq, infix(contig, lastPos, svRecord.pos)); // interim chars
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
append(levelsLargeVariants->forward, infix(levels->forward, lastPos, svRecord.pos));
append(levelsLargeVariants->reverse, infix(levels->reverse, lastPos, svRecord.pos));
appendValue(varPoints, std::make_pair((int)length(seq), false));
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), lastPos, svRecord.pos,
'+', GenomicInterval::NORMAL));
currentPos = length(seq);
if (verbosity >= 3)
std::cerr << "append(seq, infix(contig, " << lastPos << ", " << svRecord.pos << ") " << __LINE__ << " (interim)\n";
switch (svRecord.kind)
{
case StructuralVariantRecord::INDEL:
{
if (svRecord.size > 0) // insertion
{
SEQAN_ASSERT_EQ((int)length(svRecord.seq), svRecord.size);
// Simulate methylation levels for insertion.
MethylationLevels lvls;
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
MethylationLevelSimulator methSim(*rng, *methSimOptions);
methSim.run(lvls, svRecord.seq);
}
// Append novel sequence and methylation levels.
append(seq, svRecord.seq);
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
append(levelsLargeVariants->forward, lvls.forward);
append(levelsLargeVariants->reverse, lvls.reverse);
appendValue(varPoints, std::make_pair((int)length(seq), false)); // variation point after insertion
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), -1, -1,
'+', GenomicInterval::INSERTED));
if (verbosity >= 3)
std::cerr << "append(seq, svRecord.seq (length == " << length(svRecord.seq) << ") " << __LINE__ << " (insertion)\n";
lastPos = svRecord.pos;
SEQAN_ASSERT_LT(lastPos, (int)length(contig));
// Copy out breakpoints.
breakpoints.push_back(std::make_pair(currentPos, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair((int)length(seq), variants.posToIdx(Variants::SV, i)));
currentPos = length(seq);
}
else // deletion
{
lastPos = svRecord.pos - svRecord.size;
SEQAN_ASSERT_LT(lastPos, (int)length(contig));
// Copy out breakpoint.
breakpoints.push_back(std::make_pair(currentPos, variants.posToIdx(Variants::SV, i)));
}
}
break;
case StructuralVariantRecord::INVERSION:
{
unsigned oldLen = length(seq);
append(seq, infix(contig, svRecord.pos, svRecord.pos + svRecord.size));
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
appendValue(varPoints, std::make_pair((int)length(seq), false)); // variation point at deletion
append(levelsLargeVariants->forward, infix(levels->reverse, svRecord.pos, svRecord.pos + svRecord.size));
reverse(infix(levelsLargeVariants->forward, oldLen, length(levelsLargeVariants->forward)));
append(levelsLargeVariants->reverse, infix(levels->forward, svRecord.pos, svRecord.pos + svRecord.size));
reverse(infix(levelsLargeVariants->reverse, oldLen, length(levelsLargeVariants->reverse)));
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), svRecord.pos, svRecord.pos + svRecord.size,
'-', GenomicInterval::INVERTED));
// Copy out small variant infos for inversion.
for (; itSmallVar != smallVarInfos.end() && itSmallVar->pos < svRecord.pos + svRecord.size; ++itSmallVar)
{
varInfos.push_back(*itSmallVar);
varInfos.back().pos = currentPos + svRecord.size - (varInfos.back().pos - lastPos);
}
if (verbosity >= 3)
std::cerr << "append(seq, infix(contig, " << svRecord.pos << ", " << svRecord.pos + svRecord.size << ") " << __LINE__ << " (inversion)\n";
reverseComplement(infix(seq, oldLen, length(seq)));
lastPos = svRecord.pos + svRecord.size;
SEQAN_ASSERT_LT(lastPos, (int)length(contig));
// Copy out breakpoints.
breakpoints.push_back(std::make_pair(currentPos, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair((int)length(seq), variants.posToIdx(Variants::SV, i)));
currentPos = length(seq);
}
break;
case StructuralVariantRecord::TRANSLOCATION:
{
SEQAN_ASSERT_GEQ(svRecord.targetPos, svRecord.pos + svRecord.size);
append(seq, infix(contig, svRecord.pos + svRecord.size, svRecord.targetPos));
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
appendValue(varPoints, std::make_pair((int)length(seq), false));
append(levelsLargeVariants->forward, infix(levels->forward, svRecord.pos + svRecord.size, svRecord.targetPos));
append(levelsLargeVariants->reverse, infix(levels->reverse, svRecord.pos + svRecord.size, svRecord.targetPos));
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), svRecord.pos + svRecord.size, svRecord.targetPos,
'+', GenomicInterval::NORMAL));
unsigned tmpCurrentPos = length(seq);
append(seq, infix(contig, svRecord.pos, svRecord.pos + svRecord.size));
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
appendValue(varPoints, std::make_pair((int)length(seq), false));
append(levelsLargeVariants->forward, infix(levels->forward, svRecord.pos, svRecord.pos + svRecord.size));
append(levelsLargeVariants->reverse, infix(levels->reverse, svRecord.pos, svRecord.pos + svRecord.size));
}
if (tmpCurrentPos != length(seq))
appendValue(intervals, GenomicInterval(tmpCurrentPos, length(seq), svRecord.pos, svRecord.pos + svRecord.size,
'+', GenomicInterval::NORMAL));
if (verbosity >= 3)
std::cerr << "append(seq, infix(contig, " << svRecord.pos + svRecord.size << ", " << svRecord.targetPos << ") " << __LINE__ << " (translocation)\n"
<< "append(seq, infix(contig, " << svRecord.pos << ", " << svRecord.pos + svRecord.size << ") " << __LINE__ << "\n";
lastPos = svRecord.targetPos;
SEQAN_ASSERT_LT(lastPos, (int)length(contig));
// Copy out small variant infos for translocation, shift left to right and righ to left but keep
// center intact.
for (; itSmallVar != smallVarInfos.end() && itSmallVar->pos < svRecord.pos; ++itSmallVar)
{
int offset = (int)currentPos - lastPos;
varInfos.push_back(*itSmallVar);
varInfos.back().pos += offset;
int bpLeft = svRecord.pos + svRecord.size;
int bpRight = svRecord.targetPos;
if (itSmallVar->pos < bpLeft)
varInfos.back().pos -= (svRecord.targetPos - svRecord.pos);
else if (itSmallVar->pos >= bpRight)
varInfos.back().pos += (svRecord.targetPos - svRecord.pos);
}
// Copy out breakpoints.
breakpoints.push_back(std::make_pair(currentPos, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair(currentPos + svRecord.targetPos - svRecord.pos - svRecord.size, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair((int)length(seq), variants.posToIdx(Variants::SV, i)));
currentPos = length(seq);
}
break;
case StructuralVariantRecord::DUPLICATION:
{
append(seq, infix(contig, svRecord.pos, svRecord.pos + svRecord.size));
SEQAN_ASSERT_GEQ(svRecord.targetPos, svRecord.pos + svRecord.size);
if (methSimOptions && methSimOptions->simulateMethylationLevels) // first copy
{
appendValue(varPoints, std::make_pair((int)length(seq), false));
append(levelsLargeVariants->forward, infix(levels->forward, svRecord.pos, svRecord.pos + svRecord.size));
append(levelsLargeVariants->reverse, infix(levels->reverse, svRecord.pos, svRecord.pos + svRecord.size));
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), svRecord.pos, svRecord.pos + svRecord.size,
'+', GenomicInterval::DUPLICATED));
unsigned tmpCurrentPos = length(seq);
append(seq, infix(contig, svRecord.pos + svRecord.size, svRecord.targetPos));
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
appendValue(varPoints, std::make_pair((int)length(seq), false));
append(levelsLargeVariants->forward, infix(levels->forward, svRecord.pos + svRecord.size, svRecord.targetPos));
append(levelsLargeVariants->reverse, infix(levels->reverse, svRecord.pos + svRecord.size, svRecord.targetPos));
}
if (tmpCurrentPos != length(seq))
appendValue(intervals, GenomicInterval(tmpCurrentPos, length(seq), svRecord.pos + svRecord.size, svRecord.targetPos,
'+', GenomicInterval::NORMAL));
tmpCurrentPos = length(seq);
append(seq, infix(contig, svRecord.pos, svRecord.pos + svRecord.size));
if (methSimOptions && methSimOptions->simulateMethylationLevels) // second copy
{
appendValue(varPoints, std::make_pair((int)length(seq), false));
append(levelsLargeVariants->forward, infix(levels->forward, svRecord.pos, svRecord.pos + svRecord.size));
append(levelsLargeVariants->reverse, infix(levels->reverse, svRecord.pos, svRecord.pos + svRecord.size));
}
if (tmpCurrentPos != length(seq))
appendValue(intervals, GenomicInterval(tmpCurrentPos, length(seq), svRecord.pos, svRecord.pos + svRecord.size,
'+', GenomicInterval::NORMAL));
if (verbosity >= 3)
std::cerr << "append(seq, infix(contig, " << svRecord.pos << ", " << svRecord.pos + svRecord.size << ") " << __LINE__ << " (duplication)\n"
<< "append(seq, infix(contig, " << svRecord.pos + svRecord.size << ", " << svRecord.targetPos << ") " << __LINE__ << "\n"
<< "append(seq, infix(contig, " << svRecord.pos << ", " << svRecord.pos + svRecord.size << ") " << __LINE__ << "\n";
lastPos = svRecord.targetPos;
SEQAN_ASSERT_LT(lastPos, (int)length(contig));
// Write out small variant infos for duplication.
for (; itSmallVar != smallVarInfos.end() && itSmallVar->pos < svRecord.pos + svRecord.size; ++itSmallVar)
{
int offset = (int)currentPos - lastPos;
varInfos.push_back(*itSmallVar);
varInfos.back().pos += offset;
if (itSmallVar->pos < svRecord.pos + svRecord.size)
{
varInfos.push_back(*itSmallVar);
varInfos.back().pos += (svRecord.targetPos - svRecord.pos);
}
}
// Copy out breakpoints.
breakpoints.push_back(std::make_pair(currentPos, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair(currentPos + svRecord.pos + svRecord.size - svRecord.pos, variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair(currentPos + svRecord.pos + svRecord.size - svRecord.pos + svRecord.targetPos - (svRecord.pos + svRecord.size), variants.posToIdx(Variants::SV, i)));
breakpoints.push_back(std::make_pair((int)length(seq), variants.posToIdx(Variants::SV, i)));
currentPos = length(seq);
}
break;
default:
return 1;
}
}
if (verbosity >= 3)
std::cerr << "append(seq, infix(contig, " << lastPos << ", " << length(contig) << ") "
<< __LINE__ << " (last interim)\n";
append(seq, infix(contig, lastPos, length(contig)));
if (methSimOptions && methSimOptions->simulateMethylationLevels)
{
append(levelsLargeVariants->forward, infix(levels->forward, lastPos, length(contig)));
append(levelsLargeVariants->reverse, infix(levels->reverse, lastPos, length(contig)));
SEQAN_ASSERT_EQ(length(seq), length(levelsLargeVariants->forward));
SEQAN_ASSERT_EQ(length(seq), length(levelsLargeVariants->reverse));
fixVariationLevels(*levelsLargeVariants, *rng, seq, varPoints, *methSimOptions);
}
if (currentPos != length(seq))
appendValue(intervals, GenomicInterval(currentPos, length(seq), lastPos, length(contig),
'+', GenomicInterval::NORMAL));
// Copy out small variant infos for trailing characters.
for (; itSmallVar != smallVarInfos.end(); ++itSmallVar)
{
int offset = (int)currentPos - lastPos;
varInfos.push_back(*itSmallVar);
varInfos.back().pos += offset;
}
// Build the interval trees of the positionMap.
seqan::String<PositionMap::TInterval> svIntervals, svIntervalsSTL;
for (unsigned i = 0; i < length(intervals); ++i)
appendValue(svIntervals, PositionMap::TInterval(
intervals[i].svBeginPos, intervals[i].svEndPos, intervals[i]));
for (unsigned i = 0; i < length(intervals); ++i)
if (intervals[i].smallVarBeginPos != -1) // ignore insertions
appendValue(svIntervalsSTL, PositionMap::TInterval(
intervals[i].smallVarBeginPos, intervals[i].smallVarEndPos, intervals[i]));
createIntervalTree(positionMap.svIntervalTree, svIntervals);
createIntervalTree(positionMap.svIntervalTreeSTL, svIntervalsSTL);
return 0;
}
