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// ==========================================================================
// NGS: Regions of Interest Analysis
// ==========================================================================
// Copyright (c) 2012-2026, Bernd Jagla, Institut Pasteur
// All rights reserved.
//
// Redistribution and use in source and binary forms, with or without
// modification, are permitted provided that the following conditions are met:
//
// * Redistributions of source code must retain the above copyright
// notice, this list of conditions and the following disclaimer.
// * Redistributions in binary form must reproduce the above copyright
// notice, this list of conditions and the following disclaimer in the
// documentation and/or other materials provided with the distribution.
// * Neither the name of Knut Reinert or the FU Berlin nor the names of
// its contributors may be used to endorse or promote products derived
// from this software without specific prior written permission.
//
// THIS SOFTWARE IS PROVIDED BY THE COPYRIGHT HOLDERS AND CONTRIBUTORS "AS IS"
// AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE
// IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE
// ARE DISCLAIMED. IN NO EVENT SHALL KNUT REINERT OR THE FU BERLIN BE LIABLE
// FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL
// DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR
// SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER
// CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT
// LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY
// OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH
// DAMAGE.
//
// ==========================================================================
// Author: Manuel Holtgrewe <manuel.holtgrewe@fu-berlin.de>
// ==========================================================================
#include "roi_builder.h"
// ---------------------------------------------------------------------------
// Static Members
// ---------------------------------------------------------------------------
int RoiBuilder::nextId = 0;
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::createRoi()
// ---------------------------------------------------------------------------
// Create a new ROI.
void RoiBuilder::createRoi(seqan2::BamAlignmentRecord const & record)
{
clear(currentProfile);
clear(connective);
clear(currentRoi);
readsInCurrentRoi = 0;
currentRoi.ref = refNames[record.rID];
currentRoi.rID = record.rID;
currentRoi.beginPos = record.beginPos;
currentRoi.endPos = record.beginPos + getAlignmentLengthInRef(record);
if (options.strandSpecific)
currentRoi.strand = hasFlagRC(record) ? '-' : '+';
else
currentRoi.strand = '+'; // BED does not allow '.' here.
currentRoi.len = currentRoi.endPos - currentRoi.beginPos;
currentRoi.countMax = 0;
extendRoi(record);
}
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::extendRoi()
// ---------------------------------------------------------------------------
// Extend the current ROI.
void RoiBuilder::extendRoi(seqan2::BamAlignmentRecord const & record)
{
// We will use this for extending the connective array in case of using pairing.
bool fillConnective = false;
readsInCurrentRoi += 1;
// Apply pairing information if configured and there is any and we have the left mate.
if (options.usePairing && hasFlagMultiple(record) && record.tLen > 0)
{
if ((int)currentRoi.len < record.tLen + (record.beginPos - currentRoi.beginPos))
currentRoi.len = record.tLen + (record.beginPos - currentRoi.beginPos);
currentRoi.endPos = currentRoi.beginPos + currentRoi.len;
fillConnective = true;
}
// Apply alignment information from record.
if (currentRoi.endPos < record.beginPos + (int)getAlignmentLengthInRef(record))
{
currentRoi.endPos = record.beginPos + getAlignmentLengthInRef(record);
currentRoi.len = currentRoi.endPos - currentRoi.beginPos;
}
// Resize coverage count array and profile, case where mates are not considered.
if (length(currentRoi.count) < (unsigned)currentRoi.len)
{
resize(currentRoi.count, currentRoi.len, 0);
resize(currentProfile, currentRoi.len, TProfileChar());
resize(connective, currentRoi.len, fillConnective);
}
// Increase counts.
typedef seqan2::Iterator<seqan2::String<seqan2::CigarElement<> > const, seqan2::Rooted>::Type TCigarIt;
unsigned beginPos = record.beginPos - currentRoi.beginPos;
unsigned k = 0;
for (TCigarIt it = begin(record.cigar, seqan2::Rooted()); !atEnd(it); goNext(it))
{
switch (it->operation)
{
case 'M':
case 'X':
case '=':
for (unsigned i = 0; i < it->count; ++i, ++beginPos, ++k)
{
currentProfile[beginPos].count[ordValue(seqan2::Dna5(record.seq[k]))] += 1;
currentRoi.count[beginPos] += 1;
connective[beginPos] = true;
}
break;
case 'D':
for (unsigned i = 0; i < it->count; ++i, ++beginPos)
{
currentRoi.count[beginPos] += 1;
connective[beginPos] = true;
}
break;
case 'I':
k += 1;
break;
case 'N':
if (options.linkOverSkipped)
{
for (unsigned i = 0; i < it->count; ++i, ++beginPos)
connective[beginPos] = true;
}
else
{
beginPos += it->count;
}
break;
default:
break; // NOP
}
}
}
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::pushRecord()
// ---------------------------------------------------------------------------
void RoiBuilder::pushRecord(seqan2::BamAlignmentRecord const & record)
{
if (options.verbosity >= 2 && currentRoi.rID != record.rID)
std::cerr << "switching to rId == " << record.rID << "\n";
// static int i = 0;
// if (options.verbosity >= 2 && ++i)
// {
// if (i % 10000 == 0)
// std::cerr << "i == " << i << "\n";
// }
if (currentRoi.rID != record.rID || currentRoi.endPos < record.beginPos)
{
// The record does not overlap with the current ROI. Write out current record (if any) and start a new ROI.
writeCurrentRecord();
createRoi(record);
}
else
{
// The record overlaps with the current ROI. Extend it.
extendRoi(record);
}
}
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::writeHeader()
// ---------------------------------------------------------------------------
void RoiBuilder::writeHeader()
{
seqan2::RoiHeader header;
appendValue(header.extraColumns, "num_reads");
appendValue(header.extraColumns, "gc_content");
seqan2::writeHeader(roiFileOut, header);
}
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::writeRecord()
// ---------------------------------------------------------------------------
int RoiBuilder::writeRecord(MyRoiRecord & record,
seqan2::String<TProfileChar> const & profile)
{
// Compute maximal count.
for (unsigned i = 1; i < record.len; i++)
record.countMax = std::max(record.countMax, record.count[i]);
// Get ROI id.
std::stringstream roiIdStr;
roiIdStr << "region_" << nextId++;
record.name = roiIdStr.str();
// Add information on number of reads in region.
char buffer[100];
snprintf(buffer, 99, "%d", readsInCurrentRoi);
appendValue(record.data, buffer);
// Compute C+G content from profile.
unsigned cg = 0, at = 0;
for (unsigned i = 0; i < length(profile); ++i)
{
seqan2::Dna5 x = profile[i];
cg += (x == 'C' || x == 'G');
at += (x == 'A' || x == 'T');
}
double cgContent = (cg + at == 0) ? 0 : 1.0 * cg / (cg + at);
cgContent = floor(cgContent * 10000.0) / 10000.0; // flooring to 4 digits
snprintf(buffer, 99, "%4.4f", cgContent);
appendValue(record.data, buffer);
seqan2::writeRecord(roiFileOut, record);
return 0;
}
// ---------------------------------------------------------------------------
// Member Function RoiBuilder::writeCurrentRecord()
// ---------------------------------------------------------------------------
int RoiBuilder::writeCurrentRecord()
{
if (currentRoi.beginPos == seqan2::RoiRecord::INVALID_POS)
return 0; // Do not write out if not set.
// TODO(holtgrew): Cache that there was no N in cigar string and short circuit to writeRecord()?
// Try to find a value in connective that is false and extract infixes with consecutive stretches of 1s.
seqan2::String<seqan2::Pair<int, int> > pairs;
SEQAN_ASSERT_NOT_MSG(empty(connective), "ROI cannot be empty.");
SEQAN_ASSERT_MSG(connective[0], "First element of ROI must be match.");
int beginPos = 0;
bool state = true;
for (unsigned i = 1; i < length(connective); ++i)
{
if (state) // looking for 1/0 change
{
if (!connective[i])
{
appendValue(pairs, seqan2::Pair<int, int>(beginPos, i));
state = false;
beginPos = i;
}
}
else // looking for 0/1 change
{
if (connective[i])
{
state = true;
beginPos = i;
}
}
}
if (state && beginPos != (int)length(connective))
appendValue(pairs, seqan2::Pair<int, int>(beginPos, length(connective)));
// Easy case of all connective: Early exit.
if (length(pairs) == 1u && front(pairs).i1 == 0 && back(pairs).i2 == (int)length(connective))
return writeRecord(currentRoi, currentProfile);
// Write out connected components.
MyRoiRecord infixRecord;
seqan2::String<TProfileChar> infixProfile;
for (unsigned i = 0; i < length(pairs); ++i)
{
clear(infixRecord);
clear(infixProfile);
infixRecord = currentRoi;
infixRecord.beginPos += pairs[i].i1;
infixRecord.endPos = infixRecord.beginPos + pairs[i].i2 - pairs[i].i1;
infixRecord.len = infixRecord.endPos - infixRecord.beginPos;
infixRecord.count = infix(currentRoi.count, pairs[i].i1, pairs[i].i2);
infixProfile = infix(currentProfile, pairs[i].i1, pairs[i].i2);
int res = 0;
if ((res = writeRecord(infixRecord, infixProfile)) != 0)
return res;
}
return 0;
}
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