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// ==========================================================================
// Mason - A Read Simulator
// ==========================================================================
// Copyright (c) 2006-2026, Knut Reinert, FU Berlin
// 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 "sequencing.h"
// ===========================================================================
// Class SangerSequencingSimulator
// ===========================================================================
// ---------------------------------------------------------------------------
// Function SangerSequencingSimulator::readLength()
// ---------------------------------------------------------------------------
unsigned SangerSequencingSimulator::readLength()
{
if (sangerOptions.readLengthIsUniform)
{
// Pick uniformly.
double minLen = sangerOptions.readLengthMin;
double maxLen = sangerOptions.readLengthMax;
std::uniform_real_distribution<double> dist(minLen, maxLen);
double len = dist(rng);
return static_cast<unsigned>(round(len));
}
else
{
// Pick normally distributed.
std::normal_distribution<double> dist(sangerOptions.readLengthMean, sangerOptions.readLengthError);
double len = dist(rng);
return static_cast<unsigned>(round(len));
}
}
// ---------------------------------------------------------------------------
// Function SangerSequencingSimulator::simulateRead()
// ---------------------------------------------------------------------------
// Actually simulate read and qualities from fragment and direction forward/reverse strand.
void SangerSequencingSimulator::simulateRead(
TRead & seq, TQualities & quals, SequencingSimulationInfo & info,
TFragment const & frag, Direction dir, Strand strand)
{
// TODO(holtgrew): Pick better names for read length here.
// Pick sampled length.
unsigned sampleLength = this->readLength();
if (sampleLength > length(frag))
{
throw std::runtime_error("Sanger read is too long, increase fragment length");
}
// Simulate CIGAR string.
TCigarString cigar;
this->_simulateCigar(cigar, sampleLength);
// Simulate sequence (materialize mismatches and insertions).
typedef seqan2::ModifiedString<seqan2::ModifiedString<TFragment, seqan2::ModView<seqan2::FunctorComplement<seqan2::Dna5> > >, seqan2::ModReverse> TRevCompFrag;
if ((dir == LEFT) && (strand == FORWARD))
{
_simulateSequence(seq, rng, prefix(frag, sampleLength), cigar);
}
else if ((dir == LEFT) && (strand == REVERSE))
{
seqan2::Prefix<TFragment>::Type holder(prefix(frag, sampleLength));
_simulateSequence(seq, rng, TRevCompFrag(holder), cigar);
}
else if ((dir == RIGHT) && (strand == FORWARD))
{
_simulateSequence(seq, rng, suffix(frag, length(frag) - sampleLength), cigar);
}
else // ((dir == RIGHT) && (strand == REVERSE))
{
seqan2::Suffix<TFragment>::Type holder(suffix(frag, length(frag) - sampleLength));
_simulateSequence(seq, rng, TRevCompFrag(holder), cigar);
}
// Simulate Qualities.
this->_simulateQualities(quals, cigar, sampleLength);
// Reverse qualities if necessary.
if (strand == REVERSE)
reverse(quals);
// Write out sequencing information info if configured to do so.
if (seqOptions->embedReadInfo)
{
info.cigar = cigar;
unsigned len = 0;
_getLengthInRef(len, cigar);
if (dir == LEFT)
info.sampleSequence = prefix(frag, len);
else
info.sampleSequence = suffix(frag, length(frag) - len);
info.isForward = (strand == FORWARD);
if (strand == REVERSE)
reverseComplement(info.sampleSequence);
}
}
// ---------------------------------------------------------------------------
// Function SangerSequencingSimulator::_simulateCigar()
// ---------------------------------------------------------------------------
// Simulate CIGAR string. We can do this with position specific parameters only and thus independent of any
// context.
void SangerSequencingSimulator::_simulateCigar(TCigarString & cigar, unsigned sampleLength)
{
clear(cigar);
std::uniform_real_distribution<double> dist(0, 1);
for (unsigned i = 0; i < sampleLength;)
{
double x = dist(rng);
double pos = 1.0 * i / (sampleLength - 1);
double pMismatch = sangerOptions.probabilityMismatchBegin + pos * (sangerOptions.probabilityMismatchEnd - sangerOptions.probabilityMismatchBegin);
double pInsert = sangerOptions.probabilityInsertBegin + pos * (sangerOptions.probabilityInsertEnd - sangerOptions.probabilityInsertBegin);
double pDelete = sangerOptions.probabilityDeleteBegin + pos * (sangerOptions.probabilityDeleteEnd - sangerOptions.probabilityDeleteBegin);
double pMatch = 1.0 - pMismatch - pInsert - pDelete;
// Simulate mutation/insertion/deletion events. If possible we reuse the last CIGAR entry. Adjacent
// insertion/deletion pairs cancel each other out. We count i up to the input read length, thus using the
// "second" member of appendOperation()'s result.
if (x < pMatch) // match
{
i += appendOperation(cigar, 'M').second;
}
else if (x < pMatch + pMismatch) // point polymorphism
{
i += appendOperation(cigar, 'X').second;
}
else if (x < pMatch + pMismatch + pInsert) // insertion
{
if (i == 0 || i + 1 == sampleLength)
continue; // no indel at beginning/end
i += appendOperation(cigar, 'I').second;
}
else // deletion
{
if (i == 0 || i + 1 == sampleLength)
continue; // no indel at beginning/end
i += appendOperation(cigar, 'D').second;
}
}
}
// ---------------------------------------------------------------------------
// Function SangerSequencingSimulator::_simulateQualities()
// ---------------------------------------------------------------------------
void SangerSequencingSimulator::_simulateQualities(
TQualities & quals, TCigarString const & cigar, unsigned sampleLength)
{
clear(quals);
// unsigned pos = 0; // Position in result.
unsigned rPos = 0; // Position in fragment.
for (unsigned i = 0; i < length(cigar); ++i)
{
for (unsigned j = 0; j < cigar[i].count; ++j/*, ++pos*/)
{
double mean = 0.0, stdDev = 0.0;
double relPos = 1.0 * rPos / (1.0 * sampleLength);
rPos += (cigar[i].operation != 'D');
if (cigar[i].operation == 'D')
{
continue; // No quality to give out.
}
else if (cigar[i].operation == 'I' || cigar[i].operation == 'X')
{
mean = sangerOptions.qualityMatchStartMean + relPos * (sangerOptions.qualityMatchEndMean - sangerOptions.qualityMatchStartMean);
stdDev = sangerOptions.qualityMatchStartStdDev + relPos * (sangerOptions.qualityMatchEndStdDev - sangerOptions.qualityMatchStartStdDev);
}
else // cigar[i].operation == 'M'
{
mean = sangerOptions.qualityErrorStartMean + relPos * (sangerOptions.qualityErrorEndMean - sangerOptions.qualityErrorStartMean);
stdDev = sangerOptions.qualityErrorStartStdDev + relPos * (sangerOptions.qualityErrorEndStdDev - sangerOptions.qualityErrorStartStdDev);
}
std::normal_distribution<double> dist(mean, stdDev);
int q = static_cast<int>(dist(rng));
q = std::max(0, std::min(40, q));
appendValue(quals, (char)('!' + q));
}
}
}
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