src/hg/tcga/pBamBam/pBamBamSNP.c 1.2
1.2 2010/06/01 21:46:13 jsanborn
added new mutation caller
Index: src/hg/tcga/pBamBam/pBamBamSNP.c
===================================================================
RCS file: /projects/compbio/cvsroot/kent/src/hg/tcga/pBamBam/pBamBamSNP.c,v
retrieving revision 1.1
retrieving revision 1.2
diff -b -B -U 1000000 -r1.1 -r1.2
--- src/hg/tcga/pBamBam/pBamBamSNP.c 28 Apr 2010 00:37:21 -0000 1.1
+++ src/hg/tcga/pBamBam/pBamBamSNP.c 1 Jun 2010 21:46:13 -0000 1.2
@@ -1,1128 +1,1161 @@
/* asBamBam -- discovering variants from BAM file
* code adapted from Heng Li's Samtools library functions
*/
#ifdef USE_BAM
#include "common.h"
#include "hCommon.h"
#include "linefile.h"
#include "hash.h"
#include "hdb.h"
#include "options.h"
#include "jksql.h"
#define _IOLIB 2
#include "bam.h"
#include "sam.h"
#include "bam_helper.h"
static char const rcsid[] = "$Id";
void usage()
/* Explain usage and exit. */
{
errAbort(
"bamBamSNP - Allele-Specific BamBam.\n"
"usage:\n"
" asBamBam [options] <left.bam> <right.bam>\n"
"options:\n"
" -fa=file - FASTA filename of reference [NULL]\n"
" -position=chr1:1-100 - Position to do analysis. [NULL=process all reads]\n"
" -minSuppSNP=INT - Minimum Support for SNP/Het Calling. [4]\n"
" -minSuppSV=INT - Minimum Support for struct vars. [2]\n"
" -minQ=INT - Minimum acceptable base quality. [10]\n"
" -minMapQ=INT - Minimum acceptable mapping quality. [20]\n"
" -avgMapQ=INT - Minimum acceptable average mapping quality. [30]\n"
" -minChiSq=INT - Minimum acceptable chi square of nucleotide freqs. [250]\n"
" -fracGerm=FLOAT - Fraction of normal contamination [0.0]\n"
"\n"
);
}
static struct optionSpec options[] = {
{"fa", OPTION_STRING},
{"position", OPTION_STRING},
{"minSuppSNP", OPTION_INT},
{"minSuppSV", OPTION_INT},
{"minQ", OPTION_INT},
{"minMapQ", OPTION_INT},
{"avgMapQ", OPTION_INT},
{"minChiSq", OPTION_INT},
{"fracGerm", OPTION_FLOAT},
{NULL, 0}
};
+#define IN_PROB 0.94 // probability of getting base that's member of genotype
+ // (1.0 - IN_PROB) / 3.0 = prob of getting error
+
#define BAD_TID -999
/* Option variables */
char *faidx = NULL;
char *position = NULL;
int minSuppSNP = 4;
int minSuppSV = 2;
int minQ = 10;
int minMapQ = 20;
int avgMapQ = 30;
int minChiSq = 250;
float fracGerm = 0.0;
typedef struct {
int minQ;
int minMapQ;
int avgMapQ;
int maxISize;
int minChiSq;
int minSuppSNP;
int minSuppSV;
int sites;
int readsPerBin;
int pStartPrev;
int pStopPrev;
int pStart;
int pStop;
/* Overall Copy Number */
int32_t tid;
int32_t lstart;
int32_t lstop;
int lcounts;
int32_t rstart;
int32_t rstop;
int rcounts;
int32_t prevTid;
int32_t prevStart;
int32_t prevStop;
/* ASCN */
int32_t tidAS;
int32_t startAS;
int32_t stopAS;
int lcountsMin;
int lcountsMax;
int rcountsMin;
int rcountsMax;
/* SV */
int svStartL;
int svStopL;
int svStartR;
int svStopR;
long double fracGerm;
} analysis_params_t;
static int32_t countsL1[4];
static int32_t countsL2[4];
static int32_t countsL3[4];
static int32_t countsR1[4];
static int32_t countsR2[4];
static int32_t countsR3[4];
static int32_t votesL[4];
static int32_t countsL[4];
static int32_t votesR[4];
static int32_t countsR[4];
typedef struct {
char nuc;
int count;
int vote;
} variant_t;
variant_t minorL, majorL;
variant_t minorR, majorR;
static int32_t insL, delL, insR, delR;
typedef struct {
int tid;
int mtid;
int32_t qstart;
int32_t qstop;
int32_t mstart;
int32_t mstop;
int supp;
int qual;
int mstrand;
int qstrand;
int mdir; // trend of mate directions
int pmstart; // previos start
} sv_t;
#define BUF 100 // buffer around reads' starts/stops
static int nuc_index(char c)
{
switch (c)
{
case 'A':
return 0;
case 'G':
return 1;
case 'T':
return 2;
case 'C':
return 3;
default:
return -1;
}
return -1;
}
#define NUCS "AGTC"
static inline void reset_globals(analysis_params_t *ap)
{
/* reset nuc counts */
int i;
for (i = 0; i < 4; i++)
{ // sum up the qualities of each base
votesL[i] = 0;
countsL[i] = 0;
votesR[i] = 0;
countsR[i] = 0;
countsL1[i] = 0;
countsL2[i] = 0;
countsL3[i] = 0;
countsR1[i] = 0;
countsR2[i] = 0;
countsR3[i] = 0;
}
/* reset indel stats */
insL = 0;
insR = 0;
delL = 0;
delR = 0;
/* reset pileup info */
ap->pStart = -1, ap->pStop = -1;
}
static inline int check_read(const bam_pileup1_t *p, analysis_params_t *ap)
{
bam1_core_t *c = &p->b->core;
/* Check if unmapped or PCR optical dupe */
if (((c)->flag & BAM_FUNMAP) || ((c)->flag & BAM_FDUP) )
return 0;
/* check base quality */
if (bam1_qual(p->b)[p->qpos] < ap->minQ)
return 0;
/* check mapping quality */
if ((c)->qual < ap->minMapQ)
return 0;
/* all good */
return 1;
}
static inline void nuc_counts(dual_pileup_t *d, analysis_params_t *ap)
{
/* reset global vars */
reset_globals(ap);
int i, index;
int32_t start, stop;
int32_t prevStart = -1;
const bam_pileup1_t *p;
char best_b1 = 'N';
int best_q1 = -1;
char best_b2 = 'N';
int best_q2 = -1;
int insertion = 0, deletion = 0;
for (i = 0; i < d->nL; ++i)
{
p = d->puL + i;
if (!check_read(p, ap))
continue;
bam1_core_t *c = &p->b->core;
int qual = bam1_qual(p->b)[p->qpos];
/* Check if start & stop has already been visited, to dupes missed in prev step*/
start = (c)->pos;
stop = start + (c)->l_qseq;
if (ap->pStart == -1)
{
ap->pStart = start;
ap->pStop = stop;
}
else
{
if (start < ap->pStart)
ap->pStart = start;
if (stop > ap->pStop)
ap->pStop = stop;
}
if (prevStart == -1)
prevStart = start;
if (start < prevStart)
continue;
if (start == prevStart)
{
if (p->is_del)
{
if (p->indel > 0)
insertion = 1;
else if (p->indel < 0)
deletion = 1;
}
else
{
int b = toupper(bam_nt16_rev_table[bam1_seqi(bam1_seq(p->b), p->qpos)]);
if (best_b1 == 'N')
{
best_b1 = b;
best_q1 = qual;
}
else if (qual > best_q1)
{
best_b2 = best_b1;
best_q2 = best_q1;
best_b1 = b;
best_q1 = qual;
}
else if (qual > best_q2)
{
best_b2 = b;
best_q2 = qual;
}
}
continue;
}
prevStart = start;
if (insertion)
insL += 1;
else if (deletion)
delL += 1;
double lseq = (double) p->b->core.l_qseq;
if ((index = nuc_index(best_b1)) >= 0)
{
votesL[index] += best_q1;
countsL[index]++;
if (p->qpos < round(0.33 * lseq))
countsL1[index]++;
else if (p->qpos < round(0.67 * lseq))
countsL2[index]++;
else
countsL3[index]++;
}
if ((index = nuc_index(best_b2)) >= 0)
{
votesL[index] += best_q2;
countsL[index]++;
if (p->qpos < round(0.33 * lseq))
countsL1[index]++;
else if (p->qpos < round(0.67 * lseq))
countsL2[index]++;
else
countsL3[index]++;
}
best_b1 = 'N';
best_q1 = -1;
best_b2 = 'N';
best_q2 = -1;
insertion = 0, deletion = 0;
if (p->is_del)
{
if (p->indel > 0)
insertion = 1;
else if (p->indel < 0)
deletion = 1;
}
else
{
int b = toupper(bam_nt16_rev_table[bam1_seqi(bam1_seq(p->b), p->qpos)]);
if (best_b1 == 'N')
{
best_b1 = b;
best_q1 = qual;
}
else if (qual > best_q1)
{
best_b2 = best_b1;
best_q2 = best_q1;
best_b1 = b;
best_q1 = qual;
}
else if (qual > best_q2)
{
best_b2 = b;
best_q2 = qual;
}
}
}
prevStart = -1;
for (i = 0; i < d->nR; ++i)
{
p = d->puR + i;
if (!check_read(p, ap))
continue;
bam1_core_t *c = &p->b->core;
int qual = bam1_qual(p->b)[p->qpos];
/* Check if start & stop has already been visited, to dupes missed in prev step*/
start = (c)->pos;
stop = start + (c)->l_qseq;
if (start <= prevStart)
continue;
prevStart = start;
if (ap->pStart == -1)
{
ap->pStart = start;
ap->pStop = stop;
}
if (start < ap->pStart)
ap->pStart = start;
if (stop > ap->pStop)
ap->pStop = stop;
if (p->indel > 0)
insR += 1;
else if (p->indel < 0)
delR += 1;
if (!p->is_del && p->indel == 0)
{
double lseq = (double) p->b->core.l_qseq;
int b = toupper(bam_nt16_rev_table[bam1_seqi(bam1_seq(p->b), p->qpos)]);
if ((index = nuc_index(b)) < 0)
continue;
votesR[index] += qual;
countsR[index]++;
if (p->qpos < round(0.33 * lseq))
countsR1[index]++;
else if (p->qpos < round(0.67 * lseq))
countsR2[index]++;
else
countsR3[index]++;
}
}
int iL1 = -1, iL2 = -1, maxL1 = 0, maxL2 = 0;
int iR1 = -1, iR2 = -1, maxR1 = 0, maxR2 = 0;
int countL1 = -1, countL2 = -1, countR1 = -1, countR2 = -1;
for (i = 0; i < 4; i++)
{
if (countsL[i] > countL1)
{
iL2 = iL1; // set prev max to max2
maxL2 = maxL1;
countL2 = countL1;
iL1 = i;
maxL1 = votesL[i];
countL1 = countsL[i];
}
else if (countsL[i] > countL2)
{
iL2 = i;
maxL2 = votesL[i];
countL2 = countsL[i];
}
if (countsR[i] > countR1)
{
iR2 = iR1;
maxR2 = maxR1;
countR2 = countR1;
iR1 = i;
maxR1 = votesR[i];
countR1 = countsR[i];
}
else if (countsR[i] > countR2)
{
iR2 = i;
maxR2 = votesR[i];
countR2 = countsR[i];
}
}
majorL.nuc = 'N';
majorL.vote = 0;
majorL.count = 0;
if (iL1 != -1 && countL1 >= ap->minSuppSNP)
{
majorL.nuc = NUCS[iL1];
majorL.vote = maxL1;
majorL.count = countL1;
}
minorL.nuc = 'N';
minorL.vote = 0;
minorL.count = 0;
if (iL2 != -1 && countL2 >= ap->minSuppSNP)
{
minorL.nuc = NUCS[iL2];
minorL.vote = maxL2;
minorL.count = countL2;
}
majorR.nuc = 'N';
majorR.vote = 0;
majorR.count = 0;
if (iR1 != -1 && countR1 >= ap->minSuppSNP)
{
majorR.nuc = NUCS[iR1];
majorR.vote = maxR1;
majorR.count = countR1;
}
minorR.nuc = 'N';
minorR.vote = 0;
minorR.count = 0;
if (iR2 != -1 && countR2 >= ap->minSuppSNP)
{
minorR.nuc = NUCS[iR2];
minorR.vote = maxR2;
minorR.count = countR2;
}
}
double chi_square(int obs1, int obs2, double p) // p = binomial prob of getting 1
{
double pseudo = 1.0;
int count = obs1 + obs2;
double exp1 = p * ((double) count) + pseudo;
double exp2 = (1.0 - p) * ((double) count) + pseudo;
// apply Yates correction... will often have small observed values.
return pow(abs((double)obs1 - exp1) - 0.5, 2.0)/exp1 + pow(abs((double)obs2 - exp2) - 0.5, 2.0)/exp2;
}
static int sig_diff(dual_pileup_t *d, analysis_params_t *ap)
{
int i;
double pseudo = 1.0;
int totalL = 0, totalR = 0;
for (i = 0; i < 4; i++)
{
totalL += countsL[i];
totalR += countsR[i];
}
double obs, exp, chi_sq = 0.0;
for (i = 0; i < 4; i++)
{
obs = ((double) countsL[i] * 100.0) / (double) totalL + pseudo;
exp = ((double) countsR[i] * 100.0) / (double) totalR + pseudo;
chi_sq += pow(abs(obs - exp) - 0.5, 2.0) / exp;
}
return chi_sq;
}
static int is_mut(dual_pileup_t *d, analysis_params_t *ap, char *ref,
char *callL1, char *callL2, char *callR1, char *callR2)
{
if (majorR.vote == 0 || majorL.vote == 0)
return 0; // most likely a bad quality region.
if (sig_diff(d, ap) < ap->minChiSq)
return 0;
int i = 0;
int rCount = 0;
for (i = 0; i < 4; i++)
rCount += countsR1[i] + countsR2[i] + countsR3[i];
if (rCount < 10)
return 0;
char rb = (d->ref && (int)d->posL < d->len)? d->ref[d->posL] : 'N';
int retVal1 = 0, retVal2 = 0;
for (i = 0; i < 4; i++)
{
if (NUCS[i] != majorL.nuc && NUCS[i] != minorL.nuc)
continue;
if (NUCS[i] == majorL.nuc && majorL.nuc != majorR.nuc && majorL.nuc != minorR.nuc)
{
if (countsL1[i] > 0 && countsL2[i] > 0 && countsL1[i] + countsL2[i] >= 3)
retVal1 = 1;
else if (countsL1[i] > 0 && countsL3[i] > 0 && countsL1[i] + countsL3[i] >= 3)
retVal1 = 1;
else if (countsL2[i] > 0 && countsL3[i] > 0 && countsL2[i] + countsL3[i] >= 3)
retVal1 = 1;
if (retVal1)
{
if (rCount >= 30 && countsR[i] <= 1)
retVal1 = 1;
else if (rCount < 30 && countsR[i] == 0)
retVal1 = 1;
else
retVal1 = 0;
}
}
if (NUCS[i] == minorL.nuc && (minorL.nuc != majorR.nuc && minorL.nuc != minorR.nuc))
{
if (countsL1[i] > 0 && countsL2[i] > 0 && countsL1[i] + countsL2[i] >= 3)
retVal2 = 1;
else if (countsL1[i] > 0 && countsL3[i] > 0 && countsL1[i] + countsL3[i] >= 3)
retVal2 = 1;
else if (countsL2[i] > 0 && countsL3[i] > 0 && countsL2[i] + countsL3[i] >= 3)
retVal2 = 1;
if (retVal2)
{
if (rCount >= 30 && countsR[i] <= 1)
retVal2 = 1;
else if (rCount < 30 && countsR[i] == 0)
retVal2 = 1;
else
retVal2 = 0;
}
}
}
if (!retVal1 && !retVal2)
return 0;
*ref = rb;
*callL1 = majorL.nuc;
*callL2 = minorL.nuc;
*callR1 = majorR.nuc;
*callR2 = minorR.nuc;
if (majorL.nuc != majorR.nuc && majorL.nuc != minorR.nuc)
return 1;
if (minorL.nuc != 'N' && (minorL.nuc != majorR.nuc && minorL.nuc != minorR.nuc))
return 1;
return 0;
}
void print_seq(uint32_t tid, uint32_t pos, int n,
const bam_pileup1_t *pu, dual_pileup_t *d)
{
int i, rb;
rb = (d->ref && (int)pos < d->len)? d->ref[pos] : 'N';
for (i = 0; i < n; ++i)
{
const bam_pileup1_t *p = pu + i;
if (p->b->core.qual < minMapQ)
continue;
int qual = bam1_qual(p->b)[p->qpos];
if (qual < minQ)
continue;
if (!p->is_del)
{
int c = bam_nt16_rev_table[bam1_seqi(bam1_seq(p->b), p->qpos)];
c = toupper(c);
putchar(c);
}
}
return;
putchar('\t');
// print base quality
for (i = 0; i < n; ++i)
{
const bam_pileup1_t *p = pu + i;
if (p->b->core.qual < minMapQ)
continue;
int qual = bam1_qual(p->b)[p->qpos];
if (qual < minQ)
continue;
int c = qual + 33;
if (c > 126)
c = 126;
putchar(c);
}
putchar('\t');
// print mapping quality
for (i = 0; i < n; ++i)
{
const bam_pileup1_t *p = pu + i;
int qual = p->b->core.qual;
if (qual < minMapQ)
continue;
if (bam1_qual(p->b)[p->qpos] < minQ)
continue;
int c = qual + 33;
if (c > 126)
c = 126;
putchar(c);
}
}
static void print_nuc_info()
{
int i, first = 1;
for (i = 0; i < 4; i++)
{
if (countsR[i] == 0)
continue;
if (!first)
putchar(' ');
printf("%c:%d/%2.1f", NUCS[i], countsR[i], (double) votesR[i] / (double) countsR[i]);
first = 0;
}
putchar('\t');
first = 1;
for (i = 0; i < 4; i++)
{
if (countsL[i] == 0)
continue;
if (!first)
putchar(' ');
printf("%c:%d/%2.1f", NUCS[i], countsL[i], (double) votesL[i] / (double) countsL[i]);
first = 0;
}
putchar('\n');
}
static void do_mut(dual_pileup_t *d, analysis_params_t *ap)
{
char ref, callL1, callL2, callR1, callR2;
if (!is_mut(d, ap, &ref, &callL1, &callL2, &callR1, &callR2))
return;
printf("MUT1\t%s\t%d\t%d\t",
d->hL->target_name[d->tidL], d->posL, d->posL + 1);
printf("%c\t", ref);
if (callR2 == 'N')
printf("%c>", callR1);
else
printf("%c/%c>", callR1, callR2);
if (callL2 == 'N')
printf("%c\t", callL1);
else
printf("%c/%c\t", callL1, callL2);
double chi_sq = sig_diff(d, ap);
printf("%f\t", chi_sq);
print_nuc_info();
}
#define A 0
#define G 1
#define T 2
#define C 3
#define NUM_NUC 4
#define AA 0
#define AG 1
#define AT 2
#define AC 3
#define GA 1
#define GG 4
#define GT 5
#define GC 6
#define TA 2
#define TG 5
#define TT 7
#define TC 8
#define CA 3
#define CG 6
#define CT 8
#define CC 9
#define NUM_GENO 10
+#define MAX_COUNT 1000
+
+static long double *logvals;
static long double **genoPrior;
static long double **mutProb;
static long double **mutProbGeno;
static long double **baseProb;
#define GENO_1 "AAAAGGGTTC"
#define GENO_2 "AGTCGTCTCC"
void initProbTables()
{
int i, j;
+logvals = (long double *)(malloc(MAX_COUNT * sizeof(long double)));
+for (i = 0; i < MAX_COUNT; i++)
+ logvals[i] = logl((long double) i + 1.0);
+
genoPrior = (long double **)(malloc(NUM_GENO * sizeof(long double*)));
for (i = 0; i < NUM_GENO; i++)
genoPrior[i] = (long double *)(malloc(NUM_NUC * sizeof(long double)));
for (i = 0; i < NUM_GENO; i++)
{
int i1 = nuc_index(GENO_1[i]);
int i2 = nuc_index(GENO_2[i]);
for (j = 0; j < NUM_NUC; j++)
{
long double val;
if (i1 == j && i2 == j)
val = 0.80;
else if (i1 == j || i2 == j)
val = 0.10;
else
val = 0.05;
genoPrior[i][j] = logl(val);
fprintf(stderr, "%c%c-%c %Lf\t", GENO_1[i], GENO_2[i], NUCS[i], genoPrior[i][j]);
}
fprintf(stderr, "\n");
}
mutProb = (long double **)(malloc(NUM_NUC * sizeof(long double*)));
for (i = 0; i < NUM_NUC; i++)
mutProb[i] = (long double *)(malloc(NUM_NUC * sizeof(long double)));
long double val, tot;
for (i = 0; i < NUM_NUC; i++)
{
tot = 0.0;
for (j = 0; j < NUM_NUC; j++)
{
/* else, transitions 4x more likely than transitions */
if (i == j)
val = 1.0;
else if ((NUCS[i] == 'A' && NUCS[j] == 'G') || (NUCS[i] == 'G' && NUCS[j] == 'A'))
val = 0.1;
else if ((NUCS[i] == 'C' && NUCS[j] == 'T') || (NUCS[i] == 'T' && NUCS[j] == 'C'))
val = 0.1;
else
val = 0.025;
mutProb[i][j] = val;
tot += val;
}
/* normalize probs, conditioned on germline call */
for (j = 0; j < NUM_NUC; j++)
{
mutProb[i][j] = logl(mutProb[i][j]/tot);
fprintf(stderr, "%c%c %Lf\t", NUCS[i], NUCS[j], mutProb[i][j]);
}
fprintf(stderr, "\n");
}
mutProbGeno = (long double **)(malloc(NUM_GENO * sizeof(long double*)));
for (i = 0; i < NUM_GENO; i++)
mutProbGeno[i] = (long double *)(malloc(NUM_GENO * sizeof(long double)));
for (i = 0; i < NUM_GENO; i++)
{
int i1 = nuc_index(GENO_1[i]);
int i2 = nuc_index(GENO_2[i]);
for (j = 0; j < NUM_GENO; j++)
{
int j1 = nuc_index(GENO_1[j]);
int j2 = nuc_index(GENO_2[j]);
long double val1 = mutProb[i1][j1] + mutProb[i2][j2];
long double val2 = mutProb[i1][j2] + mutProb[i2][j1];
if (val1 > val2)
mutProbGeno[i][j] = val1;
else
mutProbGeno[i][j] = val2;
fprintf(stderr, "%c%c->%c%c %Lf\t", GENO_1[i], GENO_2[i], GENO_1[j], GENO_2[j], mutProbGeno[i][j]);
}
fprintf(stderr, "\n");
}
baseProb = (long double **)(malloc(NUM_GENO * sizeof(long double*)));
for (i = 0; i < NUM_GENO; i++)
baseProb[i] = (long double *)(malloc(NUM_NUC * sizeof(long double)));
-long double inprob = 0.9;
+long double inprob = IN_PROB;
long double outprob = (1.0 - inprob) / 3.0;
for (i = 0; i < NUM_GENO; i++)
{
int i1 = nuc_index(GENO_1[i]);
int i2 = nuc_index(GENO_2[i]);
for (j = 0; j < NUM_NUC; j++)
{
if (i1 == j && i2 == j)
baseProb[i][j] = inprob;
else if (i1 == j || i2 == j)
baseProb[i][j] = (inprob + outprob) / 2.0;
else
baseProb[i][j] = outprob;
baseProb[i][j] = logl(baseProb[i][j]);
fprintf(stderr, "%c%c-%c %Lf\t", GENO_1[i], GENO_2[i], NUCS[j], baseProb[i][j]);
}
fprintf(stderr, "\n");
}
}
static long double dataProbGerm(int geno)
{
int i, j, tot = 0;
long double p = 0.0, scale = 0.0;
for (i = 0; i < NUM_NUC; i++)
{
p += (long double) countsR[i] * baseProb[geno][i];
tot += countsR[i];
for (j = 0; j < countsR[i]; j++)
- scale -= logl((long double) (j + 1.0));
+ scale -= logvals[j];
}
for (i = 0; i < tot; i++)
- scale += logl((long double) (i + 1.0));
+ scale += logvals[i];
return p + scale;
}
static long double dataProbTum(int genoG, int genoT, long double alpha)
{
int i, j, tot = 0;
long double p = 0.0, scale = 0.0;
for (i = 0; i < NUM_NUC; i++)
{
p += (long double) countsL[i] * (alpha * baseProb[genoG][i] + (1.0 - alpha) * baseProb[genoT][i]);
tot += countsL[i];
for (j = 0; j < countsL[i]; j++)
- scale -= logl((long double) (j + 1.0));
+ scale -= logvals[j];
}
for (i = 0; i < tot; i++)
- scale += logl((long double) (i + 1.0));
+ scale += logvals[i];
return p + scale;
}
static int is_mut_prob(dual_pileup_t *d, analysis_params_t *ap, char *ref,
char *callL1, char *callL2, char *callR1, char *callR2,
long double *conf)
{
if (majorR.vote == 0 || majorL.vote == 0)
return 0; // most likely a bad quality region.
int i, j, imax = -1, jmax = -1;
int totalL = 0, totalR = 0;
for (i = 0; i < NUM_NUC; i++)
{
totalL += countsL[i];
totalR += countsR[i];
}
+if (totalL < ap->minSuppSNP || totalR < ap->minSuppSNP)
+ return 0;
+
+/* rescale counts to total to less than MAX_COUNT, if exceeded */
+if (totalL > MAX_COUNT)
+ for (i = 0; i < NUM_NUC; i++)
+ countsL[i] = (int) floor((float) countsL[i] * (float) MAX_COUNT / (float) totalL);
+if (totalR > MAX_COUNT)
+ for (i = 0; i < NUM_NUC; i++)
+ countsR[i] = (int) floor((float) countsR[i] * (float) MAX_COUNT / (float) totalR);
+
long double alpha = (ap->fracGerm * (long double) totalR) / (long double) totalL;
if (alpha > ap->fracGerm)
alpha = ap->fracGerm;
-char rb = (d->ref && (int)d->posL < d->len)? toupper(d->ref[d->posL]) : 'N';
+char rb = (d->ref && (int)d->posL < d->len) ? toupper(d->ref[d->posL]) : 'N';
int ri = nuc_index(rb);
+int i1, i2, j1, j2;
long double p, ptot = 0.0, pmax = -999999999.99;
for (i = 0; i < NUM_GENO; i++)
{ // loop germline genotypes
+ i1 = nuc_index(GENO_1[i]);
+ i2 = nuc_index(GENO_2[i]);
+ if (!countsL[i1] && !countsL[i2] && !countsR[i1] && !countsR[i2])
+ continue; // skip genotypes
+
+ long double germP = 0.0;
+ if (ri >= 0)
+ germP = genoPrior[i][ri];
+ germP += dataProbGerm(i);
+
for (j = 0; j < NUM_GENO; j++)
{ // loop tumor genotypes
- if (ri < 0)
- p = 0.0;
- else
- p = genoPrior[i][ri];
- p = 0.0;
+ j1 = nuc_index(GENO_1[j]);
+ j2 = nuc_index(GENO_2[j]);
+ if (!countsL[j1] && !countsL[j2] && !countsR[j1] && !countsR[j2])
+ continue;
+
+ p = germP;
p += mutProbGeno[i][j];
p += dataProbTum(i, j, alpha);
- p += dataProbGerm(i);
+
+ ptot += expl(p);
if (p > pmax)
{
pmax = p;
imax = i;
jmax = j;
}
- ptot += expl(p);
}
}
if (imax < 0 || jmax < 0)
return 0;
*ref = rb;
*callL1 = GENO_1[jmax];
*callL2 = GENO_2[jmax];
*callR1 = GENO_1[imax];
*callR2 = GENO_2[imax];
*conf = expl(pmax) / ptot;
if (imax != jmax)
return 1;
if (GENO_1[imax] != GENO_2[imax] || (rb != GENO_1[imax] && rb != GENO_2[imax]))
return 2;
return 0;
}
static void do_mut_prob(dual_pileup_t *d, analysis_params_t *ap)
{
int ret;
char ref, callL1, callL2, callR1, callR2;
long double conf;
if ((ret = is_mut_prob(d, ap, &ref, &callL1, &callL2, &callR1, &callR2, &conf)) == 0)
return;
printf("MUT2\t%s\t%d\t%d\t",
d->hL->target_name[d->tidL], d->posL, d->posL + 1);
if (ret == 1)
printf("SOM\t");
else
printf("GERM\t");
printf("%c\t", ref);
printf("%c%c>", callR1, callR2);
printf("%c%c\t", callL1, callL2);
printf("%Lf\t", conf);
print_nuc_info();
}
static void perform_analysis(dual_pileup_t *d, void *func_data)
{
analysis_params_t *ap = (analysis_params_t *)func_data;
/* processes pileup for het and mut analysis */
nuc_counts(d, ap);
/* mutation discovery */
do_mut(d, ap); // old way
do_mut_prob(d, ap); // new way
fflush(stdout);
}
void bamBam(char *inbamL, char *inbamR, char *faidx, int mask)
{
analysis_params_t ap;
ap.minQ = minQ;
ap.minChiSq = minChiSq;
ap.minMapQ = minMapQ;
ap.avgMapQ = avgMapQ;
ap.minSuppSNP = minSuppSNP;
ap.minSuppSV = minSuppSV;
ap.sites = 0;
ap.pStart = -1;
ap.pStop = -1;
ap.pStartPrev = -1;
ap.pStopPrev = -1;
/* Overall Copy Number */
ap.tid = BAD_TID;
ap.lstart = -1;
ap.lstop = -1;
ap.lcounts = 0;
ap.rstart = -1;
ap.rstop = -1;
ap.rcounts = 0;
ap.prevTid = BAD_TID;
ap.prevStart = -1;
ap.prevStop = -1;
/* ASCN */
ap.tidAS = BAD_TID;
ap.startAS = -1;
ap.stopAS = -1;
ap.lcountsMin = 0;
ap.lcountsMax = 0;
ap.rcountsMin = 0;
ap.rcountsMax = 0;
/* SV */
ap.svStartL = -1;
ap.svStopL = -1;
ap.svStartR = -1;
ap.svStopR = -1;
ap.fracGerm = (long double) fracGerm;
initProbTables();
bam_bam_file(inbamL, inbamR, faidx, position, mask, perform_analysis, &ap);
}
int main(int argc, char *argv[])
/* Process command line. */
{
optionInit(&argc, argv, options);
if (argc < 3)
usage();
if (optionExists("fa"))
faidx = optionVal("fa", NULL);
if (optionExists("position"))
position = optionVal("position", NULL);
if (optionExists("minSuppSNP"))
minSuppSNP = optionInt("minSuppSNP", 4);
if (optionExists("minSuppSV"))
minSuppSV = optionInt("minSuppSV", 2);
if (optionExists("minQ"))
minQ = optionInt("minQ", 10);
if (optionExists("minMapQ"))
minMapQ = optionInt("minMapQ", 20);
if (optionExists("avgMapQ"))
avgMapQ = optionInt("avgMapQ", 30);
if (optionExists("minChiSq"))
minChiSq = optionInt("minChiSq", 250);
if (optionExists("fracGerm"))
fracGerm = optionFloat("fracGerm", 0.0);
char *inbamL = argv[1];
char *inbamR = argv[2];
bamBam(inbamL, inbamR, faidx, BAM_DEF_MASK);
return 0;
}
#else // USE_BAM not defined
int main(int argc, char *argv[])
/* Process command line. */
{
printf("BAM not installed");
return 0;
}
#endif