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get_protein_changes.cpp
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get_protein_changes.cpp
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/* this function calculates CDS&proteins changes of all SNPs in tSNPlist */
#include <stdio.h>
#include <map>
#include <algorithm>
#include <string>
#include "globals.h"
#include "translate_as_string.h"
void get_protein_changes(GeneSNPlist* gene, multimap<unsigned long, mySNP>* tSNPlist)
{
/* 1.translate the reference CDS sequence */
std::string pro_seq("");
translate_as_string((*gene).ref_coding.substr(first_codon_frame), &pro_seq);
(*gene).protein.insert(std::pair<std::string, std::string>("ref", pro_seq));
/* 2.construct the mutant CDS sequence that will be translated into protein */
unsigned long cds_pos = 1; // ID
map<unsigned long, unsigned long>::iterator cds_exon_itr;
map<unsigned long, unsigned long>::iterator cds_exon_itr_end;
cds_exon_itr = (*gene).CDSexon.begin();
cds_exon_itr_end = (*gene).CDSexon.end();
while(cds_exon_itr != cds_exon_itr_end)
{
unsigned long icds_exon = (*cds_exon_itr).first;
while(icds_exon <= (*cds_exon_itr).second) // continuous, e.g., first=2533 ~ second=2789
{
std::string ref_base = (*gene).ref_gene.substr(icds_exon - (*gene).start, 1);
map<unsigned long, mySNP>::iterator posSNP_itr = (*gene).SNP_lists.find(icds_exon);
if( posSNP_itr != (*gene).SNP_lists.end() )
{
(*posSNP_itr).second.gene_id = (*gene).gene_id; // (*posSNP_itr) is mySNP struct
(*posSNP_itr).second.stype = "CDS";
if((*gene).orientation == "+")
{
std::pair <unsigned long, unsigned long> cds_pair;
// first=virtual(1,2,3,...,cds_length), second=real(along genome)
cds_pair = std::make_pair(cds_pos, icds_exon);
(*gene).coding_SNP.insert(cds_pair);
// virtual ID
(*posSNP_itr).second.cds_pos = cds_pos;
// relative position - caution here: correctness not checked - 2013-04-15 23:57
(*posSNP_itr).second.gene_pos = icds_exon - (*gene).start + 1;
}
else if((*gene).orientation == "-")
{
// caution here: correctness not checked - 2013-04-16 00:04
unsigned long real_pos = (*gene).cds_length - cds_pos + 1;
std::pair <unsigned long, unsigned long> cds_pair;
cds_pair = std::make_pair(real_pos, icds_exon);
(*gene).coding_SNP.insert(cds_pair);
(*posSNP_itr).second.cds_pos = real_pos;
(*posSNP_itr).second.gene_pos = (*gene).end - icds_exon + 1;
}
else
{
printf("Warning (get_protein_changes.cpp): orient neither '+' nor '-'. ");
printf("Check GFF format.\n");
}
(*gene).eco_coding += (*posSNP_itr).second.new_base;
}
else
{
(*gene).eco_coding += ref_base;
}
/* next position of an exon */
cds_pos ++;
icds_exon ++;
}
/* next exon */
cds_exon_itr ++;
}
if((*gene).orientation == "-")
{
std::string cseq = (*gene).eco_coding;
/* reverse sequence */
std::reverse(cseq.begin(), cseq.end());
/* lowercase sequence */
std::transform(cseq.begin(), cseq.end(),cseq.begin(), ::tolower);
/* complement sequence */
std::replace(cseq.begin(), cseq.end(), 'a', 'T');
std::replace(cseq.begin(), cseq.end(), 'c', 'G'); // caution1: here c:G
std::replace(cseq.begin(), cseq.end(), 'g', 'C'); // caution2: here g:C
std::replace(cseq.begin(), cseq.end(), 't', 'A'); // if caution 1&2 is not consistent,
std::replace(cseq.begin(), cseq.end(), 'u', 'A'); // they will result in c:G+G:C=c:C
(*gene).eco_coding.clear();
(*gene).eco_coding = cseq;
}
/* 3.translate the mutant CDS sequence */
std::string pro_mut_seq("");
translate_as_string((*gene).eco_coding.substr(first_codon_frame), &pro_mut_seq);
(*gene).protein.insert(std::pair<std::string, std::string>("alt", pro_mut_seq));
/* 4.get protein changes position by position */
for(unsigned long j_prot_pos = 1; j_prot_pos <= (*gene).protein["alt"].length(); j_prot_pos ++)
{
map<std::string, std::string>::iterator protein_itr;
protein_itr = (*gene).protein.find("ref");
std::string ref_aa = (*protein_itr).second.substr(j_prot_pos-1, 1);
protein_itr = (*gene).protein.find("alt");
std::string new_aa = (*protein_itr).second.substr(j_prot_pos-1, 1);
map<unsigned long, unsigned long>::iterator codingSNP_itr;
/* note: protein position <=> DNA 3 positions: 1=1/2/3, 2=4/5/6, 3=7/8/9, 4=10/11/12, ... */
/* there is a possibility for these positions to be SNPs */
/* check if a SNP position 3*j_prot_pos-2+first_codon_frame exists for protein position j_prot_pos */
codingSNP_itr = (*gene).coding_SNP.find(3*j_prot_pos - 2 + first_codon_frame);
if(codingSNP_itr != (*gene).coding_SNP.end())
{
unsigned long genome_position = (*codingSNP_itr).second; // real position along genome
map<unsigned long, mySNP>::iterator gpos_itr = (*gene).SNP_lists.find(genome_position);
if(gpos_itr == (*gene).SNP_lists.end())
{
printf("Warning (get_protein_changes.cpp): genome position not found.\n");
}
else
{
(*gpos_itr).second.codon_pos = 1;
(*gpos_itr).second.ref_aa = ref_aa;
(*gpos_itr).second.new_aa = new_aa;
if(ref_aa != new_aa)
{
/* AA change */
std::pair <unsigned long, unsigned long> chg_pair;
chg_pair = std::make_pair(j_prot_pos, 1);
(*gene).AA_changes.insert(chg_pair);
/* DNA change */
chg_pair = std::make_pair(3*j_prot_pos-2, genome_position);
(*gene).NS_changes.insert(chg_pair);
(*gpos_itr).second.ns_change = 1;
/* stop codon change */
if(new_aa == "*")
{
(*gpos_itr).second.new_stop = 1;
}
else
if(ref_aa == "*")
{
(*gpos_itr).second.lost_stop = 1;
}
}
}
} // end of SNP on 3*j_prot_pos - 2
/* check if a SNP position 3*j_prot_pos-1 exists for protein position j_prot_pos */
codingSNP_itr = (*gene).coding_SNP.find(3*j_prot_pos - 1 + first_codon_frame); //diff1
if(codingSNP_itr != (*gene).coding_SNP.end())
{
unsigned long genome_position = (*codingSNP_itr).second; // real position along genome
map<unsigned long, mySNP>::iterator gpos_itr = (*gene).SNP_lists.find(genome_position);
if(gpos_itr == (*gene).SNP_lists.end())
{
printf("Warning (get_protein_changes.cpp): genome position not found.\n");
}
else
{
(*gpos_itr).second.codon_pos = 2; // diff2
(*gpos_itr).second.ref_aa = ref_aa;
(*gpos_itr).second.new_aa = new_aa;
if(ref_aa != new_aa)
{
std::pair <unsigned long, unsigned long> chg_pair;
chg_pair = std::make_pair(j_prot_pos, 1);
(*gene).AA_changes.insert(chg_pair);
chg_pair = std::make_pair(3*j_prot_pos-1, genome_position); // diff3
(*gene).NS_changes.insert(chg_pair);
(*gpos_itr).second.ns_change = 1;
if(new_aa == "*")
{
(*gpos_itr).second.new_stop = 1;
}
else
if(ref_aa == "*")
{
(*gpos_itr).second.lost_stop = 1;
}
}
}
} // end of SNP on 3*j_prot_pos - 1
/* check if a SNP position 3*j_prot_pos exists for protein position j_prot_pos */
codingSNP_itr = (*gene).coding_SNP.find(3*j_prot_pos + first_codon_frame); //diff1
if(codingSNP_itr != (*gene).coding_SNP.end())
{
unsigned long genome_position = (*codingSNP_itr).second; // real position along genome
map<unsigned long, mySNP>::iterator gpos_itr = (*gene).SNP_lists.find(genome_position);
if(gpos_itr == (*gene).SNP_lists.end())
{
printf("Warning (get_protein_changes.cpp): genome position not found.\n");
}
else
{
(*gpos_itr).second.codon_pos = 3; //diff2
(*gpos_itr).second.ref_aa = ref_aa;
(*gpos_itr).second.new_aa = new_aa;
if(ref_aa != new_aa)
{
std::pair <unsigned long, unsigned long> chg_pair;
chg_pair = std::make_pair(j_prot_pos, 1);
(*gene).AA_changes.insert(chg_pair);
chg_pair = std::make_pair(3*j_prot_pos, genome_position); // diff3
(*gene).NS_changes.insert(chg_pair);
(*gpos_itr).second.ns_change = 1;
if(new_aa == "*")
{
(*gpos_itr).second.new_stop = 1;
}
else
if(ref_aa == "*")
{
(*gpos_itr).second.lost_stop = 1;
}
}
}
} // end of SNP on 3*j_prot_pos
} // end of step 4.
(*tSNPlist).clear(); // optimization: only need to update gene-related SNPs. - 2013-04-16 21:01
(*tSNPlist).insert( (*gene).SNP_lists.begin(), (*gene).SNP_lists.end() );
}
/* a gene struct:
(*gene).gene_id = gene_name; //1 std::string
(*gene).isoform = isoform; // std::string
(*gene).chromosome = chromosome; // std::string
(*gene).start = singleGENEann.start; // unsigned long
(*gene).end = singleGENEann.end; //5 unsigned long
(*gene).cds_length = 0; // unsigned long
(*gene).protein_length = 0; // unsigned long
(*gene).orientation = singleGENEann.orien; // std::string
(*gene).SNP_lists = snp_list; // map<unsigned long, mySNP>
(*gene).coding_SNP.clear(); //10 map<unsigned long, unsigned long>
(*gene).NS_changes.clear(); // map<unsigned long, unsigned long>
(*gene).AA_changes.clear(); // map<unsigned long, unsigned long>
(*gene).CDSexon.clear(); // map<unsigned long, unsigned long>
(*gene).protein.clear(); // map<std::string, std::string>
(*gene).ref_gene = singleGENEann.seq; //15 std::string
(*gene).ref_coding.clear(); // std::string
(*gene).eco_coding.clear(); //17 std::string
*/
/* initialization of mySNP struct* iSNP:
(*iSNP).ecotype = "";
(*iSNP).chromosome = "";
(*iSNP).position = 0;
(*iSNP).stype = "intergenic";
(*iSNP).gene_id = "NA";
(*iSNP).gene_pos = 0;
(*iSNP).cds_pos = 0;
(*iSNP).codon_pos = 0;
(*iSNP).ns_change = 0;
(*iSNP).new_stop = 0;
(*iSNP).lost_stop = 0;
(*iSNP).splicechange = 0;
(*iSNP).ref_base = "";
(*iSNP).new_base = "";
(*iSNP).ref_aa = "";
(*iSNP).new_aa = "";
//map<std::string, std::string>domain_change;
(*iSNP).support = 0;
(*iSNP).concordance = 0.0;
(*iSNP).quality = 0;
(*iSNP).peak_distance = 999999999;
(*iSNP).marker_ratio = 0.0;
(*iSNP).source = "IlluminaGA2";
*/