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#include "piler2.h"
#if defined(DEBUG) && defined(_MSC_VER)
#include <crtdbg.h>
#endif
#define GFFRecord GFFRecord2
/***
Find LTR families.
1. LTR candidates
------===--------------------===------------ genome
^----------------------^
Hit
Hit is candidate pair of LTRs bounding a candidate LINE if:
(a) hit length >= MIN_LENGTH_LTR and <= MAX_LENGTH_LTR, and
(b) offset is >= MIN_LENGTH_LINE and <= MAX_LENGTH_LINE.
2. Same family if a local alignment connects two LTR candidates
of similar length.
Cand A Cand B
------===........===----------===........===----- genome
^------------^
Hit
***/
static int MIN_LENGTH_LINE = 50;
static int MAX_LENGTH_LINE = 12000;
static int MIN_LENGTH_LTR = 50;
static int MAX_LENGTH_LTR = 2000;
static double MIN_LINE_RATIO = 0.9;
static int MIN_FAM_SIZE = 3;
static double MIN_HIT_LENGTH_RATIO = 0.5;
static int MIN_DIST_EDGE = 50000;
static EdgeList Edges;
static double Ratio(int i, int j)
{
if (i == 0 && j == 0)
return 0;
if (i < j)
return (double) i / (double) j;
else
return (double) j / (double) i;
}
static int GetHitLength(const HitData &Hit)
{
const int QueryHitLength = Hit.QueryTo - Hit.QueryFrom + 1;
const int TargetHitLength = Hit.TargetTo - Hit.TargetFrom + 1;
return (QueryHitLength + TargetHitLength)/2;
}
static int GetLTRLength(const HitData &Hit)
{
const int QueryLTRLength = Hit.QueryTo - Hit.QueryFrom + 1;
const int TargetLTRLength = Hit.TargetTo - Hit.TargetFrom + 1;
return (QueryLTRLength + TargetLTRLength)/2;
}
static int GetHitFrom(const HitData &Hit)
{
return min(Hit.QueryFrom, Hit.TargetFrom);
}
static int GetHitTo(const HitData &Hit)
{
return max(Hit.QueryTo, Hit.TargetTo);
}
static int GetLINELength(const HitData &Hit)
{
return GetHitTo(Hit) - GetHitFrom(Hit) + 1;
}
static bool IsCandLTR(const HitData &Hit)
{
const int LTRLength = GetLTRLength(Hit);
if (LTRLength < MIN_LENGTH_LTR || LTRLength > MAX_LENGTH_LTR)
return false;
const int LINELength = GetLINELength(Hit);
if (LINELength < MIN_LENGTH_LINE || LINELength > MAX_LENGTH_LINE)
return false;
return true;
}
static HitData *Cands;
static int CandCount = 0;
static int CandBufferSize = 0;
static void AddCand(const HitData &Hit, IIX &IntervalIndex)
{
if (CandCount >= CandBufferSize)
{
CandBufferSize += 10000;
Cands = reall(Cands, HitData, CandBufferSize);
}
int From;
int To;
if (Hit.QueryFrom < Hit.TargetFrom)
{
From = Hit.QueryFrom;
To = Hit.TargetTo;
}
else
{
From = Hit.TargetFrom;
To = Hit.TargetTo;
}
IntervalIndex.AddGlobal(From, To, CandCount);
Cands[CandCount++] = Hit;
}
static bool TooClose(const GLIX &HitGlix, const HitData &Hit1, const HitData &Hit2)
{
const int Hit1From = Hit1.QueryFrom;
const int Hit2From = Hit2.QueryFrom;
int SeqFrom1;
int SeqFrom2;
const char *Label1 = HitGlix.GlobalToSeq(Hit1From, &SeqFrom1);
const char *Label2 = HitGlix.GlobalToSeq(Hit2From, &SeqFrom2);
if (0 != strcmp(Label1, Label2))
return false;
return iabs(SeqFrom2 - SeqFrom1) < MIN_DIST_EDGE;
}
static bool IsEdge(const GLIX &HitGlix, const HitData &Hit, int i, int j)
{
if (i == j)
return false;
assert(i >= 0 && i < CandCount);
assert(j >= 0 && j < CandCount);
const HitData &Hit_i = Cands[i];
const HitData &Hit_j = Cands[j];
const int HitLength = GetHitLength(Hit);
const int HitLength_i = GetHitLength(Hit_i);
const int HitLength_j = GetHitLength(Hit_j);
if (Ratio(HitLength, HitLength_i) < MIN_HIT_LENGTH_RATIO ||
Ratio(HitLength, HitLength_j) < MIN_HIT_LENGTH_RATIO ||
Ratio(HitLength_i, HitLength_j) < MIN_HIT_LENGTH_RATIO)
return false;
const int LINELength_i = GetLINELength(Hit_i);
const int LINELength_j = GetLINELength(Hit_j);
if (Ratio(LINELength_i, LINELength_j) < MIN_LINE_RATIO)
return false;
if (TooClose(HitGlix, Hit_i, Hit_j))
return false;
return true;
}
static void FindEdges(const HitData &Hit, const GLIX &HitGlix, const IIX &IntervalIndex)
{
int *QueryMatches;
int *TargetMatches;
const int QueryMatchCount = IntervalIndex.LookupGlobal(Hit.QueryFrom, Hit.QueryTo, &QueryMatches);
const int TargetMatchCount = IntervalIndex.LookupGlobal(Hit.TargetFrom, Hit.TargetTo, &TargetMatches);
const int MatchCount = QueryMatchCount + TargetMatchCount;
int *Matches = all(int, MatchCount);
memcpy(Matches, QueryMatches, QueryMatchCount*sizeof(int));
memcpy(Matches + QueryMatchCount, TargetMatches, TargetMatchCount*sizeof(int));
for (int i = 0; i < MatchCount; ++i)
{
const int m = Matches[i];
if (m < 0 || m > CandCount)
Quit("m=%d count=%d", m, CandCount);
}
for (int i = 0; i < MatchCount; ++i)
{
const int CandIndex1 = Matches[i];
for (int j = 0; j < i; ++j)
{
const int CandIndex2 = Matches[j];
if (IsEdge(HitGlix, Hit, CandIndex1, CandIndex2))
{
EdgeData Edge;
Edge.Node1 = CandIndex1;
Edge.Node2 = CandIndex2;
Edge.Rev = Hit.Rev;
Edges.push_back(Edge);
}
}
}
}
static void WriteOutputFile(FILE *fOut, const GLIX &HitGlix, FamList &Fams)
{
GFFRecord Rec;
Rec.Feature = "tr";
Rec.Source = "piler";
Rec.Score = 0;
Rec.Strand = '.';
Rec.Frame = -1;
int FamIndex = 0;
for (PtrFamList p = Fams.begin(); p != Fams.end(); ++p)
{
FamData *Fam = *p;
for (PtrFamData q = Fam->begin(); q != Fam->end(); ++q)
{
FamMemberData &FamMember = *q;
int CandIndex = FamMember.PileIndex;
assert(CandIndex >= 0 && CandIndex < CandCount);
const HitData &Hit = Cands[CandIndex];
const int GlobalFrom = GetHitFrom(Hit);
const int GlobalTo = GetHitTo(Hit);
const int Length = GlobalTo - GlobalFrom + 1;
int SeqFrom;
const char *Label = HitGlix.GlobalToSeq(GlobalFrom, &SeqFrom);
int SeqTo = SeqFrom + Length - 1;
Rec.SeqName = Label;
Rec.Start = SeqFrom + 1;
Rec.End = SeqTo + 1;
Rec.Strand = (FamMember.Rev ? '-' : '+');
char Attrs[1024];
sprintf(Attrs, "Family %d ; Cand %d", FamIndex, CandIndex);
Rec.Attrs = Attrs;
WriteGFFRecord(fOut, Rec);
}
++FamIndex;
}
}
static void WriteCands(FILE *f, const GLIX &HitGlix)
{
GFFRecord Rec;
for (int CandIndex = 0; CandIndex < CandCount; ++CandIndex)
{
const HitData &Hit = Cands[CandIndex];
char AnnotBuffer[1024];
HitToGFFRecord(HitGlix, Hit, Rec, AnnotBuffer);
char s[4096];
sprintf(s, "%s ; Cand %d", Rec.Attrs, CandIndex);
Rec.Attrs = s;
WriteGFFRecord(f, Rec);
}
}
void TR()
{
#if defined(DEBUG) && defined(_MSC_VER)
_CrtSetDbgFlag(0); // too expensive
#endif
const char *HitFileName = RequiredValueOpt("tr");
const char *OutFileName = RequiredValueOpt("out");
const char *CandFileName = ValueOpt("cand");
const char *strMinTrSpacing = ValueOpt("mintrspacing");
const char *strMaxTrSpacing = ValueOpt("maxtrspacing");
const char *strMinTrLength = ValueOpt("mintrlength");
const char *strMaxTrLength = ValueOpt("minspacingratio");
const char *strMinFam = ValueOpt("minfam");
const char *strMinHitRatio = ValueOpt("minhitratio");
const char *strMinDistPairs = ValueOpt("mindistpairs");
if (0 != strMinTrSpacing)
MIN_LENGTH_LINE = atoi(strMinTrSpacing);
if (0 != strMaxTrSpacing)
MAX_LENGTH_LINE = atoi(strMaxTrSpacing);
if (0 != strMinTrLength)
MIN_LENGTH_LTR = atoi(strMinTrLength);
if (0 != strMaxTrLength)
MAX_LENGTH_LTR = atoi(strMaxTrLength);
if (0 != strMinFam)
MIN_FAM_SIZE = atoi(strMinFam);
if (0 != strMinHitRatio)
MIN_HIT_LENGTH_RATIO = atoi(strMinHitRatio);
if (0 != strMinDistPairs)
MIN_DIST_EDGE = atoi(strMinDistPairs);
FILE *fHit = OpenStdioFile(HitFileName, FILEIO_MODE_ReadOnly);
ProgressStart("Index hits");
GLIX HitGlix;
HitGlix.Init();
HitGlix.FromGFFFile(fHit);
HitGlix.MakeGlobalToLocalIndex();
ProgressDone();
const int GlobalLength = HitGlix.GetGlobalLength();
IIX IntervalIndex;
IntervalIndex.Init(GlobalLength);
ProgressStart("Find candidate TRs");
Rewind(fHit);
GFFRecord Rec;
while (GetNextGFFRecord(fHit, Rec))
{
HitData Hit;
GFFRecordToHit(HitGlix, Rec, Hit);
if (IsCandLTR(Hit))
AddCand(Hit, IntervalIndex);
}
ProgressDone();
Progress("%d candidates", CandCount);
if (0 != CandFileName)
{
ProgressStart("Write candidates");
FILE *fCand = OpenStdioFile(CandFileName, FILEIO_MODE_WriteOnly);
WriteCands(fCand, HitGlix);
ProgressDone();
}
ProgressStart("Make graph");
Rewind(fHit);
while (GetNextGFFRecord(fHit, Rec))
{
HitData Hit;
GFFRecordToHit(HitGlix, Rec, Hit);
FindEdges(Hit, HitGlix, IntervalIndex);
}
fclose(fHit);
fHit = 0;
ProgressDone();
Progress("%d edges", (int) Edges.size());
ProgressStart("Find families");
FamList Fams;
FindConnectedComponents(Edges, Fams, MIN_FAM_SIZE);
ProgressDone();
Progress("%d families", (int) Fams.size());
FILE *fOut = OpenStdioFile(OutFileName, FILEIO_MODE_WriteOnly);
WriteOutputFile(fOut, HitGlix, Fams);
}
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