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#include <sstream>
#include <vector>
#include <alignment/statistics/StatUtils.hpp>
#include <pbdata/CommandLineParser.hpp>
#include <pbdata/FASTAReader.hpp>
#include <pbdata/FASTASequence.hpp>
#include <pbdata/utils.hpp>
/*
ref000001 . SNV 9454 9454 0.00 . . reference=C;confidence=0;Name=9454C>A;coverage=0;variantseq=A
ref000001 . deletion 20223 20223 0.00 . . reference=T;length=1;confidence=0;coverage=0;Name=20222delT
ref000001 . insertion 35089 35089 0.00 . . confidence=0;Name=35089_35090insC;reference=.;length=1;coverage=0;variantseq=C
*/
char ToLower(char c, bool useToLower)
{
if (useToLower) {
return tolower(c);
} else {
return toupper(c);
}
}
int main(int argc, char* argv[])
{
CommandLineParser clp;
std::string refGenomeName;
std::string mutGenomeName;
std::string gffFileName;
float insRate = 0;
float delRate = 0;
float mutRate = 0;
bool lower = false;
gffFileName = "";
clp.RegisterStringOption("refGenome", &refGenomeName, "Reference genome.", true);
clp.RegisterStringOption("mutGenome", &mutGenomeName, "Mutated genome.", true);
clp.RegisterPreviousFlagsAsHidden();
clp.RegisterStringOption("gff", &gffFileName,
"GFF file describing the modifications made to the genome.");
clp.RegisterFloatOption("i", &insRate, "Insertion rate: (0-1].",
CommandLineParser::NonNegativeFloat, false);
clp.RegisterFloatOption("d", &delRate, "Deletion rate: (0-1]",
CommandLineParser::NonNegativeFloat, false);
clp.RegisterFloatOption("m", &mutRate, "Mutation rate, even across all nucleotides: (0-1]",
CommandLineParser::NonNegativeFloat, false);
clp.RegisterFlagOption("lower", &lower, "Make mutations in lower case", false);
std::vector<std::string> leftovers;
clp.ParseCommandLine(argc, argv, leftovers);
FASTAReader reader;
FASTASequence refGenome;
reader.Init(refGenomeName);
std::ofstream mutGenomeOut;
CrucialOpen(mutGenomeName, mutGenomeOut, std::ios::out);
std::ofstream gffOut;
if (gffFileName != "") {
CrucialOpen(gffFileName, gffOut, std::ios::out);
}
std::vector<int> insIndices, delIndices, subIndices;
int readIndex = 0;
InitializeRandomGeneratorWithTime();
while (reader.GetNext(refGenome)) {
insIndices.resize(refGenome.length);
delIndices.resize(refGenome.length);
subIndices.resize(refGenome.length);
std::fill(insIndices.begin(), insIndices.end(), false);
std::fill(delIndices.begin(), delIndices.end(), false);
std::fill(subIndices.begin(), subIndices.end(), 0);
enum ChangeType
{
Ins,
Del,
Mut,
None
};
float changeProb[4];
changeProb[Ins] = insRate;
changeProb[Del] = changeProb[Ins] + delRate;
changeProb[Mut] = changeProb[Del] + mutRate;
changeProb[None] = 1;
if (changeProb[Mut] > 1) {
std::cout << "ERROR! The sum of the error probabilities must be less than 1"
<< std::endl;
std::exit(EXIT_FAILURE);
}
DNALength pos;
float randomNumber;
int numIns = 0;
int numDel = 0;
int numMut = 0;
for (pos = 0; pos < refGenome.length; pos++) {
randomNumber = Random();
if (randomNumber < changeProb[Ins]) {
insIndices[pos] = true;
numIns++;
} else if (randomNumber < changeProb[Del]) {
delIndices[pos] = true;
numDel++;
} else if (randomNumber < changeProb[Mut]) {
Nucleotide newNuc = TwoBitToAscii[RandomInt(4)];
int maxIts = 100000;
int it = 0;
while (newNuc == refGenome.seq[pos]) {
newNuc = TwoBitToAscii[RandomInt(4)];
if (it == maxIts) {
std::cout
<< "ERROR, something is wrong with the random number generation, it "
"took too many tries to generate a new nucleotide"
<< std::endl;
std::exit(EXIT_FAILURE);
}
}
subIndices[pos] = refGenome[pos];
refGenome.seq[pos] = ToLower(newNuc, lower);
++numMut;
}
}
// std::cout << readIndex << " m " << numMut << " i " << numIns << " d " << numDel << std::endl;
if (readIndex % 100000 == 0 && readIndex > 0) {
std::cout << readIndex << std::endl;
}
//
// Now add the insertions and deletions.
//
FASTASequence newSequence;
DNALength newPos;
if (numIns - numDel + static_cast<int>(refGenome.length) < 0) {
std::cout << "ERROR, the genome has been deleted to nothing." << std::endl;
std::exit(EXIT_FAILURE);
}
ResizeSequence(newSequence, refGenome.length + (numIns - numDel));
newPos = 0;
pos = 0;
for (pos = 0; pos < refGenome.length; pos++) {
assert(newPos < newSequence.length or delIndices[pos] == true);
if (subIndices[pos] != 0 and gffFileName != "") {
gffOut << refGenome.GetName() << " . SNV " << newPos << " " << newPos
<< " 0.00 . . reference=" << (char)subIndices[pos]
<< ";confidence=10;Name=" << newPos << (char)subIndices[pos] << ">"
<< refGenome.seq[pos] << ";coverage=10;variantseq=" << refGenome.seq[pos]
<< std::endl;
}
if (insIndices[pos] == true) {
newSequence.seq[newPos] = ToLower(TwoBitToAscii[RandomInt(4)], lower);
newPos++;
newSequence.seq[newPos] = refGenome.seq[pos];
assert(newSequence.seq[newPos] != '1');
assert(newSequence.seq[newPos] != 1);
if (gffFileName != "") {
gffOut << refGenome.GetName() << " . deletion " << newPos << " " << newPos
<< " 0.00 . . reference=" << newSequence.seq[newPos]
<< ";length=1;confidence=10;coverage=0;Name=" << newPos << "del"
<< newSequence.seq[newPos] << std::endl;
}
newPos++;
} else if (delIndices[pos] == true) {
// no-op, skip
if (gffFileName != "") {
gffOut << refGenome.GetName() << " . insertion " << newPos << " " << newPos
<< " 0.00 . . confidence=10;Name=" << newPos << "_ins"
<< refGenome.seq[pos] << ";reference=.;length=1;coverage=0;variantseq="
<< refGenome.seq[newPos] << std::endl;
//ref000001 . deletion 20223 20223 0.00 . . reference=T;length=1;confidence=0;coverage=0;Name=20222delT
}
} else {
newSequence.seq[newPos] = refGenome.seq[pos];
newPos++;
}
}
std::stringstream titlestrm;
titlestrm << " mutated ins " << insRate << " del " << delRate << " mut " << mutRate;
newSequence.CopyTitle(refGenome.title);
newSequence.AppendToTitle(titlestrm.str());
newSequence.PrintSeq(mutGenomeOut);
newSequence.Free();
readIndex++;
}
}
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