/**
* Classifies variants.
*/
int32_t VariantManip::classify_variant(bcf_hdr_t *h, bcf1_t *v, Variant& var)
{
bcf_unpack(v, BCF_UN_STR);
const char* chrom = bcf_get_chrom(h, v);
uint32_t pos1 = bcf_get_pos1(v);
char** allele = bcf_get_allele(v);
int32_t n_allele = bcf_get_n_allele(v);
int32_t pos0 = pos1-1;
var.ts = 0;
var.tv = 0;
var.ins = 0;
var.del = 0;
var.clear(); // this sets the type to VT_REF by default.
bool homogeneous_length = true;
char* ref = allele[0];
int32_t rlen = strlen(ref);
//if only ref allele, skip this entire for loop
for (size_t i=1; i<n_allele; ++i)
{
int32_t type = VT_REF;
//check for tags
if (strchr(allele[i],'<'))
{
size_t len = strlen(allele[i]);
if (len>=5)
{
//VN/d+
if (allele[i][0]=='<' && allele[i][1]=='V' && allele[i][2]=='N' && allele[i][len-1]=='>' )
{
for (size_t j=3; j<len-1; ++j)
{
if (allele[i][j]<'0' || allele[i][j]>'9')
{
type = VT_VNTR;
}
}
}
//VNTR
else if (len==6 &&
allele[i][0]=='<' &&
allele[i][1]=='V' && allele[i][2]=='N' && allele[i][3]=='T' && allele[i][4]=='R' &&
allele[i][5]=='>' )
{
type = VT_VNTR;
}
//ST/d+
else if (allele[i][0]=='<' && allele[i][1]=='S' && allele[i][2]=='T' && allele[i][len-1]=='>' )
{
for (size_t j=3; j<len-1; ++j)
{
if (allele[i][j]<'0' || allele[i][j]>'9')
{
type = VT_VNTR;
}
}
}
//STR
else if (len==5 &&
allele[i][0]=='<' &&
allele[i][1]=='S' && allele[i][2]=='T' && allele[i][3]=='R' &&
allele[i][4]=='>' )
{
type = VT_VNTR;
}
}
if (type==VT_VNTR)
{
type = VT_VNTR;
var.type |= type;
var.alleles.push_back(Allele(type));
}
else
{
type = VT_SV;
var.type |= type;
std::string sv_type(allele[i]);
var.alleles.push_back(Allele(type, sv_type));
}
}
else if (allele[i][0]=='.' || strcmp(allele[i],allele[0])==0)
{
type = VT_REF;
}
else
{
kstring_t REF = {0,0,0};
kstring_t ALT = {0,0,0};
ref = allele[0];
char* alt = allele[i];
int32_t alen = strlen(alt);
if (rlen!=alen)
{
homogeneous_length = false;
}
//trimming
//this is required in particular for the
//characterization of multiallelics and
//in general, any unnormalized variant
int32_t rl = rlen;
int32_t al = alen;
//trim right
while (rl!=1 && al!=1)
{
if (ref[rl-1]==alt[al-1])
{
--rl;
--al;
}
else
{
break;
}
}
//trim left
while (rl !=1 && al!=1)
{
if (ref[0]==alt[0])
{
++ref;
++alt;
--rl;
--al;
}
else
{
break;
}
}
kputsn(ref, rl, &REF);
kputsn(alt, al, &ALT);
ref = REF.s;
alt = ALT.s;
int32_t mlen = std::min(rl, al);
int32_t dlen = al-rl;
int32_t diff = 0;
int32_t ts = 0;
int32_t tv = 0;
if (mlen==1 && dlen)
{
char ls, le, ss;
if (rl>al)
{
ls = ref[0];
le = ref[rl-1];
ss = alt[0];
}
else
{
ls = alt[0];
le = alt[al-1];
ss = ref[0];
}
if (ls!=ss && le!=ss)
{
++diff;
if ((ls=='G' && ss=='A') ||
(ls=='A' && ss=='G') ||
(ls=='C' && ss=='T') ||
(ls=='T' && ss=='C'))
{
++ts;
}
else
{
++tv;
}
}
}
else
{
for (int32_t j=0; j<mlen; ++j)
{
if (ref[j]!=alt[j])
{
++diff;
if ((ref[j]=='G' && alt[j]=='A') ||
(ref[j]=='A' && alt[j]=='G') ||
(ref[j]=='C' && alt[j]=='T') ||
(ref[j]=='T' && alt[j]=='C'))
{
++ts;
}
else
{
++tv;
}
}
}
}
//substitution variants
if (mlen==diff)
{
type |= mlen==1 ? VT_SNP : VT_MNP;
}
//indel variants
if (dlen)
{
type |= VT_INDEL;
}
//clumped SNPs and MNPs
if (diff && diff < mlen) //internal gaps
{
type |= VT_CLUMPED;
}
var.type |= type;
var.alleles.push_back(Allele(type, diff, alen, dlen, mlen, ts, tv));
var.ts += ts;
var.tv += tv;
var.ins = dlen>0?1:0;
var.del = dlen<0?1:0;
if (REF.m) free(REF.s);
if (ALT.m) free(ALT.s);
}
}
if (var.type==VT_VNTR)
{
bcf_unpack(v, BCF_UN_INFO);
//populate motif, motif len etc. etc.
// char* str = NULL;
// int32_t n = 0;
// int32_t ret = bcf_get_info_string(h, v, "MOTIF", &str, &n);
// if (ret>0)
// {
// var.motif = std::string(str);
// var.mlen = var.motif.size();
// }
// ret = bcf_get_info_string(h, v, "RU", &str, &n);
// if (ret>0)
// {
// var.ru = std::string(str);
// var.mlen = var.ru.size();
// }
// if (n) free(str);
//
// int32_t* no = NULL;
// n = 0;
// ret = bcf_get_info_int32(h, v, "RL", &no, &n);
// if (ret>0) var.rlen = *no;
// if (n) free(no);
//
// int32_t* fl = NULL;
// n = 0;
// ret = bcf_get_info_int32(h, v, "REF", &fl, &n);
// if (ret>0) var.rcn = *fl;
// if (n) free(fl);
}
//additionally define MNPs by length of all alleles
if (!(var.type&(VT_VNTR|VT_SV)) && var.type!=VT_REF)
{
if (homogeneous_length && rlen>1 && n_allele>1)
{
var.type |= VT_MNP;
}
}
return var.type;
}
/**
* Classifies variants.
*/
int32_t Variant::classify(bcf_hdr_t *h, bcf1_t *v)
{
clear();
this->h = h;
this->v = v;
bcf_unpack(v, BCF_UN_STR);
chrom.assign(bcf_get_chrom(h, v));
rid = bcf_get_rid(v);
pos1 = bcf_get_pos1(v);
end1 = bcf_get_end1(v);
char** allele = bcf_get_allele(v);
int32_t n_allele = bcf_get_n_allele(v);
int32_t pos0 = pos1-1;
bool homogeneous_length = true;
char* ref = allele[0];
int32_t rlen = strlen(ref);
if (strchr(ref, 'N'))
{
contains_N = true;
}
//if only ref allele, skip this entire for loop
for (size_t i=1; i<n_allele; ++i)
{
int32_t allele_type = VT_REF;
//check for symbolic alternative alleles
if (strchr(allele[i],'<'))
{
size_t len = strlen(allele[i]);
if (len>=5)
{
//VN/d+
if (allele[i][0]=='<' && allele[i][1]=='V' && allele[i][2]=='N' && allele[i][len-1]=='>' )
{
for (size_t j=3; j<len-1; ++j)
{
if (allele[i][j]<'0' || allele[i][j]>'9')
{
allele_type = VT_VNTR;
}
}
}
//VNTR
else if (len==6 &&
allele[i][0]=='<' &&
allele[i][1]=='V' && allele[i][2]=='N' && allele[i][3]=='T' && allele[i][4]=='R' &&
allele[i][5]=='>' )
{
allele_type = VT_VNTR;
}
//STR
else if (len==5 &&
allele[i][0]=='<' &&
allele[i][1]=='S' && allele[i][2]=='T' && allele[i][3]=='R' &&
allele[i][4]=='>' )
{
allele_type = VT_VNTR;
}
//ST/d+
else if (allele[i][0]=='<' && allele[i][1]=='S' && allele[i][2]=='T' && allele[i][len-1]=='>' )
{
type = VT_VNTR;
for (size_t j=3; j<len-1; ++j)
{
if ((allele[i][j]<'0' || allele[i][j]>'9') && allele[i][j]!='.')
{
type = VT_SV;
}
}
}
}
if (allele_type==VT_VNTR)
{
allele_type = VT_VNTR;
type |= allele_type;
alleles.push_back(Allele(allele_type));
}
else
{
allele_type = VT_SV;
type |= allele_type;
std::string sv_type(allele[i]);
alleles.push_back(Allele(allele_type, sv_type));
}
}
//checks for chromosomal breakpoints
else if (strchr(allele[i],'[')||strchr(allele[i],']'))
{
allele_type = VT_SV;
type |= allele_type;
std::string sv_type("<BND>");
alleles.push_back(Allele(allele_type, sv_type));
}
//non variant record
else if (allele[i][0]=='.' || strcmp(allele[i],allele[0])==0)
{
type = VT_REF;
}
//explicit sequence of bases
else
{
kstring_t REF = {0,0,0};
kstring_t ALT = {0,0,0};
ref = allele[0];
char* alt = allele[i];
int32_t alen = strlen(alt);
if (strchr(alt, 'N'))
{
contains_N = true;
}
if (rlen!=alen)
{
homogeneous_length = false;
}
//trimming
//this is required in particular for the
//characterization of multiallelics and
//in general, any unnormalized variant
int32_t rl = rlen;
int32_t al = alen;
//trim right
while (rl!=1 && al!=1)
{
if (ref[rl-1]==alt[al-1])
{
--rl;
--al;
}
else
{
break;
}
}
//trim left
while (rl !=1 && al!=1)
{
if (ref[0]==alt[0])
{
++ref;
++alt;
--rl;
--al;
}
else
{
break;
}
}
kputsn(ref, rl, &REF);
kputsn(alt, al, &ALT);
ref = REF.s;
alt = ALT.s;
int32_t mlen = std::min(rl, al);
int32_t dlen = al-rl;
int32_t diff = 0;
int32_t ts = 0;
int32_t tv = 0;
if (mlen==1 && dlen)
{
char ls, le, ss;
if (rl>al)
{
ls = ref[0];
le = ref[rl-1];
ss = alt[0];
}
else
{
ls = alt[0];
le = alt[al-1];
ss = ref[0];
}
if (ls!=ss && le!=ss)
{
++diff;
if ((ls=='G' && ss=='A') ||
(ls=='A' && ss=='G') ||
(ls=='C' && ss=='T') ||
(ls=='T' && ss=='C'))
{
++ts;
}
else
{
++tv;
}
}
}
else
{
for (int32_t j=0; j<mlen; ++j)
{
if (ref[j]!=alt[j])
{
++diff;
if ((ref[j]=='G' && alt[j]=='A') ||
(ref[j]=='A' && alt[j]=='G') ||
(ref[j]=='C' && alt[j]=='T') ||
(ref[j]=='T' && alt[j]=='C'))
{
++ts;
}
else
{
++tv;
}
}
}
}
//substitution variants
if (mlen==diff)
{
allele_type |= mlen==1 ? VT_SNP : VT_MNP;
}
//indel variants
if (dlen)
{
allele_type |= VT_INDEL;
}
//clumped SNPs and MNPs
if (diff && diff < mlen) //internal gaps
{
allele_type |= VT_CLUMPED;
}
type |= allele_type;
alleles.push_back(Allele(type, diff, alen, dlen, mlen, ts, tv));
ts += ts;
tv += tv;
ins = dlen>0?1:0;
del = dlen<0?1:0;
if (REF.m) free(REF.s);
if (ALT.m) free(ALT.s);
}
}
if (type==VT_VNTR)
{
update_vntr_from_info_fields(h, v);
}
//additionally define MNPs by length of all alleles
if (!(type&(VT_VNTR|VT_SV)) && type!=VT_REF)
{
if (homogeneous_length && rlen>1 && n_allele>1)
{
type |= VT_MNP;
}
}
return type;
}
