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#ifndef G_GAP_ASSEM_DEFINED
#define G_GAP_ASSEM_DEFINED
#include "GFastaFile.h"
#include "gdna.h"
#include "GList.hh"
#include "GHash.hh"
#include <ctype.h>
class GSeqAlign;
class MSAColumns;
extern const unsigned char GA_flag_IS_REF;
extern const unsigned char GA_flag_HAS_PARENT;
extern const unsigned char GA_flag_BAD_ALIGN;
extern const unsigned char GA_flag_PREPPED;
struct SeqDelOp {
int pos;
bool revcompl;
SeqDelOp(int p, bool r) { pos=p; revcompl=r;}
//
bool operator==(SeqDelOp& d){
return (this==&d);
}
bool operator<(SeqDelOp& d){
return (this<&d);
}
};
class GASeq : public FastaSeq {
protected:
int numgaps; //total number of accumulated gaps in this sequence
short *ofs; //array of gaps at each position;
//a negative value (-1) means DELETION of the nucleotide
//at that position!
#ifdef ALIGN_COVERAGE_DATA
int* cov; //coverage of every nucleotide of this seq
// it starts with 0 by itself
// it'll be decreased by -1 for mismatching ends!
#endif
GList<SeqDelOp> delops; //delete operations
void prepSeq(); //reverse complement if needed, and apply deletions (delops)
//should only be called once when the MSA is complete (by GSeqAlign::finalize())
public:
unsigned char flags; //8 general purpose boolean flags (bits)
// bad_align flag is the last bit -- i.e. bit 7
// all the others (0..6) are free for custom use
GSeqAlign* msa;
int msaidx; //actual index at which this sequence is to be found in GASeqAlign;
int seqlen; // exactly the size of ofs[]
int offset; //offset in the layout
int ng_ofs; //non-gapped offset in the layout
//(approx, for clipping constraints only)
char revcompl; //0 = forward, 1=reverse
int ext5; // layout-positional extension at 5' end
int ext3; // layout-positional extension at 3' end
//--
int clp5; //ever "disproved" region at 5' end
int clp3; //ever "disproved" region at 3' end
//------- comparison operators (for GList) :
//sorting by offset in cluster
void allupper() {
for (int i=0;i<len;i++) {
seq[i]=toupper(seq[i]);
}
}
void lowercase() {
for (int i=0;i<len;i++) {
seq[i]=tolower(seq[i]);
}
}
void reverseComplement() {
if (len==0) return;
//ntCompTableInit();
reverseChars(seq,len);
for (int i=0;i<len;i++) seq[i]=ntComplement(seq[i]);
}
bool operator==(GASeq& d){
return (offset==d.offset && strcmp(id,d.id)==0);
}
bool operator>(GASeq& d){
return (offset>d.offset);
}
bool operator<(GASeq& d){
return (offset<d.offset);
}
friend class GSeqAlign;
//-------------------------------
GASeq(FastaSeq& faseq, bool takeover=false);
GASeq(GASeq& aseq); //copy constructor
GASeq(const char* sname=NULL,int slen=0):FastaSeq(sname),
numgaps(0), ofs(NULL), delops(false, true, false),flags(0),msa(NULL),
msaidx(-1), seqlen(slen), offset(0),
ng_ofs(0),revcompl(0), ext5(0), ext3(0),
clp5(0), clp3(0) {
if (seqlen>0) {
GCALLOC(ofs, seqlen * sizeof(short));
#ifdef ALIGN_COVERAGE_DATA
GCALLOC(cov,seqlen*sizeof(int));
#endif
}
};
GASeq(const char* sname, const char* sdescr=NULL, const char* sseq=NULL, int slen=0, int soffset=0);
GASeq(const char* sname, int soffset, int slen, int sclipL=0, int sclipR=0, char rev=0);
~GASeq();
void refineClipping(GDynArray<char>& cons, int cpos, bool skipDels=false);
void setGap(int pos, short gaplen=1); // set the gap in this pos
void addGap(int pos, short gapadd); //extend the gap in this pos
//bitno is 0 based here, for simplicity:
inline void setFlag(unsigned char bitno) { flags |= ((unsigned char)1 << bitno); }
inline void clearFlag(unsigned char bitno) { flags ^= ((unsigned char)1 << bitno); }
inline bool hasFlag(unsigned char bitno) { return ( (((unsigned char)1 << bitno) & flags) !=0 ); }
int getNumGaps() { return numgaps; }
int gap(int pos) { return ofs[pos]; }
void removeBase(int pos); //remove the nucleotide at that position
int endOffset() { return offset+seqlen+numgaps; }
int endNgOffset() { return ng_ofs+seqlen; }
int removeClipGaps(); //remove gaps within clipped regions
//offset should be corrected appropriately!
void printGappedSeq(FILE* f, int baseoffs=0);
void printGappedSeq(int baseoffs=0) { printGappedSeq(stdout, baseoffs); }
void printGappedFasta(FILE* f);
void printMFasta(FILE* f, int llen=60); //offset padded
//void loadProcessing(); //to be called immediately after loading the sequence
// it will revCompl if needed and apply delops
void finalize(); //delete inserts and reverse complement sequence if needed
#ifdef ALIGN_COVERAGE_DATA
void addCoverage(GASeq* s);
#endif
void reverseGaps(); //don't update offset and flags
//useful after reading mgblast gap info
void revComplement(int alignlen=0);
void toMSA(MSAColumns& msa, int nucValue=1);
};
// -- nucleotide origin -- for every nucleotide in a MSA column
// this info is needed by SNP reporting
class NucOri {
public:
GASeq* seq;
int pos; //0-based position of nucleotide letter
NucOri() { seq=NULL; pos=0; }
NucOri(GASeq* s, int p) { seq=s; pos=p; }
bool operator==(NucOri& d){
return (strcmp(seq->id,d.seq->id)==0 && pos==d.pos);
}
bool operator>(NucOri& d){
int cmp=strcmp(seq->id,d.seq->id);
if (cmp==0) return pos>d.pos;
else return cmp>0;
}
bool operator<(NucOri& d){
int cmp=strcmp(seq->id,d.seq->id);
if (cmp==0) return pos<d.pos;
else return cmp<0;
}
};
struct SeqClipOp {
GASeq* seq;
int clp[2];
SeqClipOp(GASeq* s, int newclp5, int newclp3=-1) {
seq=s;
clp[0]=newclp5;
clp[1]=newclp3;
}
//--
bool operator==(SeqClipOp& d){
return (this==&d);
}
bool operator>(SeqClipOp& d){
return (this>&d);
}
bool operator<(SeqClipOp& d){
return (this<&d);
}
};
class AlnClipOps :public GList<SeqClipOp> {
public:
char q_rev;
int d5;
int d3;
//---
int total;
AlnClipOps():GList<SeqClipOp>(false,true,false) {
total=0;
d5=0;
d3=0;
q_rev=false;
}
bool add5(GASeq* s, int clp, float clipmax) {
if (s->clp5<clp) {
if (clipmax>0) {
int maxovh = clipmax>1 ? (int)clipmax : iround(clipmax * (float)s->seqlen);
if (clp>maxovh) return false;
}
//----- base test: the read should be left with no less than 25% of its length
if (s->seqlen-s->clp3-clp < (s->seqlen >> 2)) return false;
total+=10000+clp-s->clp5;
Add(new SeqClipOp(s,clp,-1));
}
return true;
}
bool add3(GASeq* s, int clp, float clipmax) {
if (s->clp3<clp) {
if (clipmax>0) {
int maxovh = clipmax>1 ? (int)clipmax : iround(clipmax * (float)s->seqlen);
if (clp>maxovh) return false;
}
//----- base test: if the read is left with less than 25% of its length
if (s->seqlen-s->clp5-clp < (s->seqlen >> 2)) return false;
total+= 10000+clp-s->clp3;
Add(new SeqClipOp(s,-1,clp));
}
return true;
}
bool add(GASeq* s, int clp5, int clp3, float clipmax) {
int newclp5=-1;
int newclp3=-1;
int add=0;
if (s->clp5<clp5) {
if (clipmax>0) {
int maxovh = clipmax>1 ? (int)clipmax : iround(clipmax * (float)s->seqlen);
if (clp5>maxovh) return false;
}
//----- base test: if the read is left with less than 25% of its length!
if (s->seqlen-s->clp3-clp5 < (s->seqlen >> 2)) return false;
add+= 10000+clp5-s->clp5;
newclp5=clp5;
}
else clp5=s->clp5;
if (s->clp3<clp3) {
if (clipmax>0) {
int maxovh = clipmax>1 ? (int)clipmax : iround(clipmax * (float)s->seqlen);
if (clp3>maxovh) return false;
}
//----- base test: if the read is left with less than 25% of its length!
if (s->seqlen-clp5-clp3 < (s->seqlen >> 2)) return false;
add+=10000+clp3-s->clp3;
newclp3=clp3;
}
if (add>0) {
total+=add;
Add(new SeqClipOp(s,newclp5,newclp3));
}
return true;
}
};
class GAlnColumn {
protected:
struct NucCount {
char nt; // A, C, G, T, N or -
// precisely in this order (except after qsort)
int count;
void set(char l, int num=0) { nt=l;count=num; }
};
enum { ncA=0, ncC, ncG, ncT, ncN, ncGap };
NucCount counts[6];
bool countsSorted;
public:
bool hasClip;
char consensus;
int layers; //total "thickness"
NucOri* clipnuc;
GList<NucOri>* nucs;
friend int qsortnuc(const void* p1, const void* p2);
//int total() { return numgaps+numN+numA()+numC()+numG()+numT(); }
GAlnColumn():countsSorted(false),hasClip(false), consensus(0),
layers(0), clipnuc(NULL), nucs(NULL) { //sorted?, free?, unique?
nucs=new GList<NucOri>(false,true,false);
/*lstC=new GList<NucOri>(false,true,false);
lstG=new GList<NucOri>(false,true,false);
lstT=new GList<NucOri>(false,true,false);*/
counts[ncA].set('A');
counts[ncC].set('C');
counts[ncG].set('G');
counts[ncT].set('T');
counts[ncN].set('N');
counts[ncGap].set('-');
}
~GAlnColumn() {
delete nucs;
if (clipnuc!=NULL) delete clipnuc;
}
void addGap(int nucVal=1) { counts[ncGap].count+=nucVal;
layers++; //-- Not a "layer", actually
//numgaps++;
}
void addNuc(GASeq* seq, int pos, bool clipped=false, short nucVal=1) {
//assumes the seq is already loaded and reverse complemented if necessary
//position is precisely where it should be
if (clipped) {
if (hasClip==false) {
hasClip=true;
clipnuc = new NucOri(seq,pos);
}
return;
}
char c=(char)toupper(seq->seq[pos]);
switch (c) {
case 'A':nucs->Add(new NucOri(seq,pos));
counts[ncA].count+=nucVal;
layers++;
break;
case 'C':nucs->Add(new NucOri(seq,pos));
counts[ncC].count+=nucVal;
layers++;
break;
case 'G':nucs->Add(new NucOri(seq,pos));
counts[ncG].count+=nucVal;
layers++;
break;
case 'T':nucs->Add(new NucOri(seq,pos));
counts[ncT].count+=nucVal;
layers++;
break;
case '-': //this shouldn't be the case!
case '*':counts[ncGap].count+=nucVal;
layers++;
//numgaps++;
break;
default: nucs->Add(new NucOri(seq,pos));
counts[ncN].count+=nucVal;
layers++;
//numN++;
}//switch
}
char bestChar(int16_t *qscore=NULL);
void remove(); //removes a nucleotide from all involved sequences
//adjust all affected offsets in the alignment
};
// A MSA columns container
class MSAColumns {
int size;
public:
static bool removeConsGaps;
static bool refineClipping;
GAlnColumn* columns;
int baseoffset;
int mincol;
int maxcol;
MSAColumns(int len, int baseofs=0) {
columns=new GAlnColumn[len];
size=len;
baseoffset=baseofs;
mincol=INT_MAX;
maxcol=0;
}
~MSAColumns() {
size=0;
baseoffset=0;
delete[] columns;
}
GAlnColumn& operator[](int idx) {
if (idx<0 || idx>=size)
GError("MSAColumns op[]: bad index %d (size=%d)\n", idx,size);
return columns[idx];
}
int len() { return maxcol-mincol+1; }
void updateMinMax(int minc, int maxc) {
if (minc<mincol) mincol=minc;
if (maxc>maxcol) maxcol=maxc;
}
};
//-----------------------------------------------
// a sequence alignment: could be pairwise or MSA
class GSeqAlign :public GList<GASeq> {
//static unsigned int counter;
int length;
int minoffset;
//int consensus_cap;
void buildMSA(bool refWeighDown=false);
void ErrZeroCov(int col);
public:
bool refinedMSA; //if refineMSA() was applied
MSAColumns* msacolumns;
unsigned int ordnum; //order number -- when it was created
// the lower the better (earlier=higher score)
int ng_len; //ungapped length and minoffset (approximative,
int ng_minofs; // for clipping constraints only)
int badseqs;
//char* consensus; //consensus sequence (built by refineMSA())
GDynArray<char> consensus;
GDynArray<int16_t> consensus_bq;
//int consensus_len;
friend class GASeq;
bool operator==(GSeqAlign& d){
return (this==&d);
}
bool operator>(GSeqAlign& d){
return (this>&d);
}
bool operator<(GSeqAlign& d){
return (this<&d);
}
//--
//GSeqAlign():GList<GASeq>(true,true,false), length(0), minoffset(0),
GSeqAlign():GList<GASeq>(false,true,false), length(0), minoffset(0),
refinedMSA(false), msacolumns(NULL), ordnum(0),
ng_len(0),ng_minofs(0), badseqs(0), consensus(512), consensus_bq(512) {
//default is: sorted by GASeq offset, free nodes, non-unique
}
GSeqAlign(bool sorted, bool free_elements=true, bool beUnique=false)
:GList<GASeq>(sorted,free_elements,beUnique), length(0), minoffset(0),
refinedMSA(false), msacolumns(NULL), ordnum(0),
ng_len(0),ng_minofs(0), badseqs(0), consensus(512), consensus_bq(512) {
}
//void incOrd() { ordnum = ++counter; }
void incOrd() { ordnum++; }
//first time creation from a pairwise alignment:
#ifdef ALIGN_COVERAGE_DATA
GSeqAlign(GASeq* s1, int l1, int r1, GASeq* s2, int l2, int r2);
#else
GSeqAlign(GASeq* s1, GASeq* s2);
#endif
~GSeqAlign() {
if (msacolumns!=NULL) delete msacolumns;
}
int len() { return length; }
void revComplement();
void addSeq(GASeq* s, int soffs, int ngofs);
void injectGap(GASeq* seq, int pos, int xgap);
void removeBase(GASeq* seq, int pos);
void extendConsensus(char c, int16_t bq=SHRT_MIN);
//try to propagate the planned trimming of a read
//to the whole MSA containing it
// returns false if too much is trimmed of any component read
void applyClipping(AlnClipOps& clipops);
bool evalClipping(GASeq* seq, int c5, int c3, float clipmax,
AlnClipOps& clipops);
//merge other alignment into this msa
//seq->id MUST be the same with oseq->id
// *if OK, gaps AND coverage values are propagated
// and omsa is deallocated
// *if not OK <=> the layout doesn't accept the merge
// due to clipmax constraint, then nothing happens
bool addAlign(GASeq* seq, GSeqAlign* omsa, GASeq* oseq);
void finalize(); //delete inserts and reverse complement sequences as needed
void print(FILE* f, char c=0); //debug printing one-line alignments
void print() { print(stdout); }
void removeColumn(int column);
void freeMSA();
void refineMSA(bool refWeighDown=false, bool redo_ends=false);
// find consensus, refine clipping, remove gap-columns
void writeACE(FILE* f, const char* name, bool refWeighDown=false);
void writeMSA(FILE* f, int linelen=60); //write as multi-FASTA (MAF?) file
void writeInfo(FILE* f, const char* name, bool refWeighDown=false);
};
int compareOrdnum(void* p1, void* p2);
int compareCounts(void* p1, void* p2);
#endif
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