int CReadBlastApp::AnalyzeSeqsViaBioseqs(CBioseq& left,
CBioseq_set::TSeq_set& against_seqs, bool against_prot)
{
if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(left, against_seqs, against_prot): "
<< GetStringDescr(left)
<< ", against_prot= " << against_prot << "\n";
NON_CONST_ITERATE( CBioseq_set::TSeq_set, right, against_seqs)
{
if((*right)->IsSet())
{
CBioseq_set::TSeq_set& seqs_down = (*right)->SetSet().SetSeq_set();
AnalyzeSeqsViaBioseqs(left, seqs_down, against_prot);
}
else
{
string name = GetStringDescr((*right)->GetSeq());
/*
if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(left, against_seqs, against_prot): "
<< "right seq entry "
<< name << "\n";
*/
if( ( against_prot && is_prot_entry((*right)->GetSeq())) ||
(!against_prot && !is_prot_entry((*right)->GetSeq()))
)
AnalyzeSeqsViaBioseqs(left, (*right)->SetSeq() );
}
}
return -1;
}
int CReadBlastApp::AnalyzeSeqsViaBioseqs(
CBioseq_set::TSeq_set& in_pool_seqs,
CBioseq_set::TSeq_set& against_seqs,
bool in_pool_prot, bool against_prot)
{
if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(in_pool_seqs, against_seqs, in_pool_prot, against_prot): "
<< ", in_pool_prot= " << in_pool_prot
<< ", against_prot= " << against_prot << "\n";
NON_CONST_ITERATE( CBioseq_set::TSeq_set, left, in_pool_seqs)
{
if((*left)->IsSet())
{
CBioseq_set::TSeq_set& seqs_down = (*left)->SetSet().SetSeq_set();
AnalyzeSeqsViaBioseqs(seqs_down, against_seqs, in_pool_prot, against_prot);
}
else
{
string name = GetStringDescr((*left)->GetSeq());
if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(in_pool_seqs, against_seqs, in_pool_prot, against_prot): "
<< "left seq entry "
<< name << "\n";
if( ( in_pool_prot && is_prot_entry((*left)->GetSeq())) ||
(!in_pool_prot && !is_prot_entry((*left)->GetSeq()))
)
{
AnalyzeSeqsViaBioseqs1((*left)->SetSeq());
AnalyzeSeqsViaBioseqs((*left)->SetSeq(), against_seqs, against_prot);
}
}
}
return -1;
}
int CReadBlastApp::AnalyzeSeqsViaBioseqs(CBioseq& left, CBioseq& right)
{
/*
if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(left, right): "
<< GetStringDescr(left) << ", " << GetStringDescr(right) << NcbiEndl;
*/
if(is_prot_entry(left) && !is_prot_entry(right))
{
// if(PrintDetails()) NcbiCerr << "AnalyzeSeqsViaBioseqs(left, right): going for overlaps\n";
overlaps_prot_na(left, right.GetAnnot());
}
return -1;
}
int CReadBlastApp::CollectSimpleSeqs(TSimpleSeqs& seqs)
{
// collect stuff from proteins
for(CTypeIterator< CSeq_entry > s = Begin(); s; ++s)
{
if(s->IsSet()) continue;
if(!is_prot_entry(s->GetSeq())) continue;
TSimpleSeq seq;
seq.description = GetProtName(s->GetSeq());
seq.name = GetStringDescr (s->GetSeq());
seq.type = "CDS";
seq.seq = CRef<CBioseq>(&(s->SetSeq()));
const CSeq_loc& loc = getGenomicLocation(s->GetSeq());
addLoctoSimpleSeq(seq, loc);
seqs.push_back(seq);
if(PrintDetails())
{
NcbiCerr << "DEBUG: CollectSimpleSeqs(): added loc to CDS: "
<< "(" << seq.name << ")"
<< "(" << printed_range(loc) << ")"
<< "(" << seq.key << ":" << printed_range(seq) << ")"
<< NcbiEndl;
}
}
// collect features from RNAs and genes
string name;
TSimpleSeqs genes;
for(CTypeIterator< CSeq_feat > f = Begin(); f; ++f)
{
const CSeq_loc& loc = f->GetLocation();
if(f->GetData().IsGene())
{
name = "Bad or no locus tag";
if (f->GetData().GetGene().CanGetLocus_tag())
name = f->GetData().GetGene().GetLocus_tag();
// I am assuming that each RNA feature is preceded by a gene
TSimpleSeq gene;
gene.type = "gene";
gene.locus_tag = name;
addLoctoSimpleSeq(gene, loc);
genes.push_back(gene);
if(PrintDetails())
{
NcbiCerr << "DEBUG: CollectSimpleSeqs(): added loc to gene: "
<< "(" << name << ")"
<< "(" << printed_range(loc) << ")"
<< "(" << gene.key << ":" << printed_range(gene) << ")"
<< NcbiEndl;
}
continue;
}
else if(!f->GetData().IsRna()) continue;
CRNA_ref::EType rna_type = f->GetData().GetRna().GetType();
string description="Bad or no descriptioin";
if ( rna_type == CRNA_ref::eType_tRNA )
{
if ( f->GetData().GetRna().CanGetExt() )
{
string type1;
try { type1 = Get3type(f->GetData().GetRna());}
catch (...)
{
NcbiCerr << "simple_overlaps: FATAL: cannot get aminoacid type for one trna feats" << NcbiEndl;
throw;
}
description = "tRNA:" + type1;
}
} // if tRNA
else
{
if(f->GetData().GetRna().CanGetExt() &&
f->GetData().GetRna().GetExt().IsName())
description = f->GetData().GetRna().GetExt().GetName();
}
TSimpleSeq seq;
if ( rna_type == CRNA_ref::eType_tRNA ) { seq.type = "tRNA"; }
else if ( rna_type == CRNA_ref::eType_rRNA ) { seq.type = GetRRNAtype(f->GetData().GetRna());}
else if ( rna_type == CRNA_ref::eType_premsg ) { seq.type = "premsg"; }
else if ( rna_type == CRNA_ref::eType_mRNA ) { seq.type = "mRNA"; }
else if ( rna_type == CRNA_ref::eType_snRNA ) { seq.type = "snRNA"; }
else if ( rna_type == CRNA_ref::eType_scRNA ) { seq.type = "scRNA"; }
else if ( rna_type == CRNA_ref::eType_snoRNA ) { seq.type = "snoRNA"; }
else if ( rna_type == CRNA_ref::eType_other ) { seq.type = "other RNA"; }
else { seq.type = "unknown RNA"; }
seq.name = name;
seq.description = description;
addLoctoSimpleSeq(seq, loc);
seqs.push_back(seq);
} // features
// need to tidy up before doing what is next
seqs.sort(less_simple_seq);
genes.sort(less_simple_seq);
// now go over all gene features and match them to seqs features;
// first of all do all exact locations
TSimpleSeqs::iterator seq = seqs.begin();
for(TSimpleSeqs::iterator gene = genes.begin(); gene!=genes.end(); )
{
string gene_range = printed_range(gene);
int seq_from=0, seq_to=0;
int gene_from = gene->exons[0].from;
int gene_to = gene->exons[0].to;
for(;seq!=seqs.end(); seq++)
{
string seq_range = printed_range(seq);
seq_from = seq->exons[0].from;
seq_to = seq->exons[0].to;
if(PrintDetails())
{
NcbiCerr << "DEBUG: CollectSimpleSeqs(): sliding seq " << seq_range << "(key: " << seq->key << ") to reach gene " << gene_range << "(key: " << gene->key << "), locus=" << gene->locus_tag << NcbiEndl;
}
if(gene->key<=seq->key) break;
}
if(seq==seqs.end()) break;
seq_from = seq->exons[0].from;
seq_to = seq->exons[0].to;
string seq_range = printed_range(seq);
if(PrintDetails())
{
NcbiCerr << "DEBUG: CollectSimpleSeqs(): sliding seq " << seq_range << "(key: " << seq->key << ") reached gene " << gene_range << "(key: " << gene->key << "), locus=" << gene->locus_tag << NcbiEndl;
}
seq_to = seq->exons[seq->exons.size()-1].to;
if(seq->exons[0].strand != eNa_strand_plus) // JIRA-PR-147
{
seq_to = seq->exons[0].to;
seq_from= seq->exons[seq->exons.size()-1].from;
}
gene_to = gene->exons[gene->exons.size()-1].to;
if(seq_to==gene_to && seq_from==gene_from) // match
{
seq->locus_tag = gene->locus_tag;
gene=genes.erase(gene++);
}
else gene++;
}
/////////////////////////////
// now try to assign non-exact gene-CDS matches
/////////////////////////////
seq=seqs.begin();
for(TSimpleSeqs::iterator gene = genes.begin(); gene!=genes.end(); )
{
string gene_printed_range = printed_range(gene);
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches: gene: " << gene_printed_range << NcbiEndl;
int gene_from = gene->exons[0].from;
// find first sequence that could match a gene
TSimpleSeqs::iterator seq_start=seq;
for(;seq_start!=seqs.end(); seq_start++)
{
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: trying seq_start: "
<< printed_range(seq_start) << NcbiEndl;
if(seq_start->locus_tag != "")
{
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: "
<< seq->locus_tag << ", continue..."<<NcbiEndl;
continue; // this is done
}
int seq_from = seq_start->exons[0].strand == eNa_strand_plus ? seq_start->exons[0].from : seq_start->exons[seq_start->exons.size()-1].from;
if(gene_from<=seq_from) break; // in case there are cross-origin seqs, they will be in the end of seqs list, so they will be tested the last, thus this incorrect sliding should be fine
}
if(seq_start==seqs.end()) break; // done with seqs
// now check if other ends fit
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: found seq_start: " << printed_range(seq_start) << NcbiEndl;
int seq_to = seq_start->exons[0].strand == eNa_strand_plus
? seq_start->exons[seq_start->exons.size()-1].to
: seq_start->exons[0].to;
int gene_to = gene->exons[gene->exons.size()-1].to;
if ( gene->exons[0].strand != eNa_strand_plus ) gene_to = gene->exons[0].to;
if (seq_to > gene_to)
{
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: sequences jumped over this gene, this gene does not fit any sequence, will be flagged later" << NcbiEndl;
// sequences jumped over this gene, this gene does not fit any sequence, will be flagged later
gene++;
continue;
}
// end find first sequence that could match a gene
// find first sequence that does not match a gene
TSimpleSeqs::iterator seq_end = seq_start;
int nmatches=0;
for(;seq_end!=seqs.end() &&
gene_to >= (seq_end->exons[0].strand == eNa_strand_plus
? seq_end->exons[seq_end->exons.size()-1].to
: seq_end->exons[0].to);
seq_end++)
{
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: trying to find: current_seq_end "
<< printed_range(seq_end)
<< ", gene_to = " << gene_to
<< ", seq_end.to = " << (seq_end->exons[0].strand == eNa_strand_plus
? seq_end->exons[seq_end->exons.size()-1].to
: seq_end->exons[0].to)
<< NcbiEndl;
if(seq_end->type == "CDS" && seq_end->locus_tag == "" ) nmatches++;
}
if(seq_end!=seqs.end() ) seq_end++;
if(PrintDetails())
{
if(seq_end!=seqs.end() )
NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: found seq_end: " << printed_range(seq_start) << NcbiEndl;
else
NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: found seq_end: end()" << NcbiEndl;
}
// end find first sequence that does not match a gene
if(PrintDetails())
{
if(seq_end!=seqs.end() )
NcbiCerr << "non-exact gene-CDS matches(" << nmatches << "): seq_end: " << printed_range(seq_end) << NcbiEndl;
else
NcbiCerr << "non-exact gene-CDS matches(" << nmatches << "): seq_end: end()" << NcbiEndl;
}
if(nmatches>1)
{
string range = printed_range(gene);
NcbiCerr << "CReadBlastApp::CollectSimpleSeqs: WARNING: gene["<<gene_printed_range<<"] matches several (" << nmatches << ") CDS features: "
<< "locus = " << gene->locus_tag << ", "
<< "[" << range << "]" << NcbiEndl;
}
// look at all found fits
bool gene_used=false;
// find best fit and assign locus tag only for that feature
TSimpleSeqs::iterator best_seq=seqs.end();
int best_gene_feat_fit = 0x0FFFFFFF; // intentionally less than the const in gene_feat_fit function
for(seq=seq_start; seq!=seq_end; seq++)
{
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: match: " << printed_range(seq) << NcbiEndl;
if(seq->locus_tag != "") continue; // this is done already
if(PrintDetails()) NcbiCerr << "non-exact gene-CDS matches["<<gene_printed_range<<"]: match: " << printed_range(seq)
<< " does not have a locus tag yet"
<< NcbiEndl;
/*
if(seq->type != "CDS" )
{
string range = printed_range(seq);
NcbiCerr << "CReadBlastApp::CollectSimpleSeqs: ERROR: non-CDS sequence does not have a gene with exactly the same boundaries: "
<< "type = " << seq->type << ", "
<< "name = " << seq->name << ", "
<< "[" << range << "]" << NcbiEndl;
}
else
*/
{
int fit=gene_feat_fit(seq, gene_from, gene_to);
if(fit <= best_gene_feat_fit )
{
best_seq=seq; best_gene_feat_fit = fit;
}
}
} // for(seq=seq_start; seq!=seq_end; seq++)
// found suitable seqs
if(best_seq!=seqs.end())
{
best_seq->locus_tag = gene->locus_tag;
gene_used = true;
}
// go to next gene
if(gene_used) gene=genes.erase(gene);
else gene++;
}
// swipe over seqs flag those that do not have locus tag
NON_CONST_ITERATE(TSimpleSeqs,seq, seqs)
{
if(seq->locus_tag != "")
{
if(seq->type == "CDS")
{
for(CTypeIterator<CSeq_feat> feat=::Begin(*(seq->seq)); feat; ++feat)
{
if(feat->CanGetComment() && feat->GetComment().find("Genomic Location: ") != string::npos)
{
string comment = "Genomic Location: " + seq->locus_tag;
feat->SetComment(comment);
}
}
}
continue;
}
string range = printed_range(seq);
NcbiCerr << "CReadBlastApp::CollectSimpleSeqs: ERROR: feature does not have a matching gene: "
<< "type = " << seq->type << ", "
<< "name = " << seq->name << ", "
<< "[" << range << "]" << NcbiEndl;
}
// swipe over genes and flag those that are not used
NON_CONST_ITERATE(TSimpleSeqs,gene, genes)
{
string range = printed_range(gene);
NcbiCerr << "CReadBlastApp::CollectSimpleSeqs: WARNING: gene does not match any feature: "
<< "locus = " << gene->locus_tag << ", "
<< "[" << range << "]" << NcbiEndl;
}
// w.out CTypeConstIterator
int CReadBlastApp::AnalyzeSeqs(CBioseq_set::TSeq_set& seqs)
{
CArgs args = GetArgs();
IncreaseVerbosity();
string tblFile;
if (args["outTbl"].HasValue())
tblFile = args["outTbl"].AsString();
else
tblFile = "/dev/null";
ofstream tblOut(tblFile.c_str(), IOS_BASE::app | IOS_BASE::out );
NON_CONST_ITERATE( CBioseq_set::TSeq_set, left, seqs)
{
if((*left)->IsSet())
{
if(PrintDetails())
NcbiCerr << "AnalyzeSeqs: going down: "
<< NcbiEndl;
CBioseq_set::TSeq_set& seqs2 = (*left)->SetSet().SetSeq_set();
PushVerbosity();
AnalyzeSeqs(seqs2);
PopVerbosity();
continue;
}
if(PrintDetails())
NcbiCerr << "AnalyzeSeqs: left: "
// << CSeq_id::GetStringDescr ((*left)->GetSeq(), CSeq_id::eFormat_FastA) << NcbiEndl;
<< GetStringDescr ((*left)->GetSeq()) << NcbiEndl;
/////////////////////////////////
// not a protein. Do NA stuff
if( !is_prot_entry((*left)->GetSeq()) )
{
// NA, process all RNA and what not annotations here and compare for overlaps
// CheckMissingRibosomalRNA((*left)->GetSeq().GetAnnot() );
// check overlaps of the sequence with other features
overlaps_na((*left)->GetSeq().GetAnnot() );
continue;
}
///////////////////////////////////
// compare to...
CBioseq_set::TSeq_set::iterator right = left;
bool again=true;
bool last_right=false;
while(again) // have overlaps
{
again=false;
++right;
if(!skip_toprot(right, seqs)) {last_right=true; break;}
if(PrintDetails())
{
NcbiCerr << "AnalyzeSeqs: right: "
<< GetStringDescr ((*right)->GetSeq()) << NcbiEndl;
}
// analyze for overlaps with the next one
PushVerbosity();
// if there are overlaps, keep on working on left, iterating through right
again=overlaps((*left)->GetSeq(), (*right)->GetSeq() );
PopVerbosity();
}
if (last_right) break;
if(PrintDetails())
NcbiCerr << "AnalyzeSeqs: finished lower level seq, overlaps: "
<< NcbiEndl;
}
NON_CONST_ITERATE( CBioseq_set::TSeq_set, left, seqs)
{
if((*left)->IsSet()) continue;
// does not hit. Skip
if( !has_blast_hits((*left)->GetSeq()) ) continue;
if(PrintDetails()) NcbiCerr << "AnalyzeSeqs: left: valid" << NcbiEndl;
CBioseq_set::TSeq_set::iterator right = left; ++right;
if(!skip_to_valid_seq_cand(right, seqs)) break;
if(PrintDetails()) NcbiCerr << "AnalyzeSeqs: right: valid" << NcbiEndl;
string common_subject;
bool fit_blast_result = fit_blast((*left)->GetSeq(), (*right)->GetSeq(), common_subject);
bool lhp = hasProblems((*left)->GetSeq(), m_diag, eFrameShift);
bool rhp = hasProblems((*right)->GetSeq(), m_diag, eFrameShift);
bool lhoe = hasProblems((*left)->GetSeq(), m_diag, eMayBeNotFrameShift);
bool rhoe = hasProblems((*right)->GetSeq(), m_diag, eMayBeNotFrameShift);
if(PrintDetails())
NcbiCerr << "AnalyzeSeqs: after fit_blast:"
<< fit_blast_result
<< lhp
<< lhoe
<< rhp
<< rhoe
<< NcbiEndl;
// if(fit_blast_result && (lhp && !lhoe) && (rhp && !rhoe))
if(fit_blast_result)
{
// go to the same sequence set, find first NA, add misc_feature
append_misc_feature(seqs, GetStringDescr((*left)->GetSeq()), eFrameShift);
}
if(PrintDetails())
NcbiCerr << "AnalyzeSeqs: finished lower level seq, frameshifts: "
<< NcbiEndl;
}
DecreaseVerbosity();
return -1;
}
