X-Git-Url: https://git.donarmstrong.com/?a=blobdiff_plain;f=bam2bcf.c;h=ab5bfcd20d4a6233109821846842d9996aab93a9;hb=df7cadac556f302bdd0bc48c235c2b61b699dfe1;hp=e55212ca98cbb28041fb6a6dfc46619ff595ee09;hpb=4fe4b27b44d067c21948870d9e48976662dec397;p=samtools.git

diff --git a/bam2bcf.c b/bam2bcf.c
index e55212c..ab5bfcd 100644
--- a/bam2bcf.c
+++ b/bam2bcf.c
@@ -3,7 +3,6 @@
 #include "bam.h"
 #include "kstring.h"
 #include "bam2bcf.h"
-#include "errmod.h"
 #include "bcftools/bcf.h"
 
 extern	void ks_introsort_uint32_t(size_t n, uint32_t a[]);
@@ -14,18 +13,15 @@ extern	void ks_introsort_uint32_t(size_t n, uint32_t a[]);
 
 #define CAP_DIST 25
 
-struct __bcf_callaux_t {
-	int max_bases, capQ, min_baseQ;
-	uint16_t *bases;
-	errmod_t *e;
-};
-
 bcf_callaux_t *bcf_call_init(double theta, int min_baseQ)
 {
 	bcf_callaux_t *bca;
 	if (theta <= 0.) theta = CALL_DEFTHETA;
 	bca = calloc(1, sizeof(bcf_callaux_t));
 	bca->capQ = 60;
+	bca->openQ = 40;
+	bca->extQ = 20;
+	bca->tandemQ = 100;
 	bca->min_baseQ = min_baseQ;
 	bca->e = errmod_init(1. - theta);
 	return bca;
@@ -57,7 +53,7 @@ int bcf_call_glfgen(int _n, const bam_pileup1_t *pl, int ref_base /*4-bit*/, bcf
 		const bam_pileup1_t *p = pl + i;
 		int q, b, mapQ, baseQ, is_diff, min_dist;
 		// set base
-		if (p->is_del || (p->b->core.flag&BAM_FUNMAP)) continue; // skip unmapped reads and deleted bases
+		if (p->is_del || p->is_refskip || (p->b->core.flag&BAM_FUNMAP)) continue;
 		baseQ = q = (int)bam1_qual(p->b)[p->qpos]; // base quality
 		if (q < bca->min_baseQ) continue;
 		mapQ = p->b->core.qual < bca->capQ? p->b->core.qual : bca->capQ;
@@ -87,11 +83,125 @@ int bcf_call_glfgen(int _n, const bam_pileup1_t *pl, int ref_base /*4-bit*/, bcf
 	return r->depth;
 }
 
+int bcf_call_glfgen_gap(int pos, int _n, const bam_pileup1_t *pl, bcf_callaux_t *bca, bcf_callret1_t *r)
+{
+	int i, n, n_ins, n_del;
+	memset(r, 0, sizeof(bcf_callret1_t));
+	if (_n == 0) return -1;
+
+	// enlarge the bases array if necessary
+	if (bca->max_bases < _n) {
+		bca->max_bases = _n;
+		kroundup32(bca->max_bases);
+		bca->bases = (uint16_t*)realloc(bca->bases, 2 * bca->max_bases);
+	}
+	// fill the bases array
+	memset(r, 0, sizeof(bcf_callret1_t));
+	r->indelreg = 10000;
+	n_ins = n_del = 0;
+	for (i = n = 0; i < _n; ++i) {
+		const bam_pileup1_t *p = pl + i;
+		int q, b, mapQ, indelQ, is_diff, min_dist;
+		if (p->is_del || p->is_refskip || (p->b->core.flag&BAM_FUNMAP)) continue;
+		{ // compute indel (base) quality
+			// this can be made more efficient, but realignment is the bottleneck anyway
+			int j, k, x, y, op, len = 0, max_left, max_rght, seqQ, indelreg;
+			bam1_core_t *c = &p->b->core;
+			uint32_t *cigar = bam1_cigar(p->b);
+			uint8_t *qual = bam1_qual(p->b);
+			for (k = y = 0, x = c->pos; k < c->n_cigar && y <= p->qpos; ++k) {
+				op = cigar[k]&0xf;
+				len = cigar[k]>>4;
+				if (op == BAM_CMATCH) {
+					if (pos > x && pos < x + len) break;
+					x += len; y += len;
+				} else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) y += len;
+				else if (op == BAM_CDEL || op == BAM_CREF_SKIP) x += len;
+			}
+			if (k == c->n_cigar) continue; // this actually should not happen
+			max_left = max_rght = 0; indelreg = 0;
+			if (pos == x + len - 1 && k+2 < c->n_cigar && ((cigar[k+1]&0xf) == BAM_CINS || (cigar[k+1]&0xf) == BAM_CDEL)
+				&& (cigar[k+2]&0xf) == BAM_CMATCH)
+			{
+				for (j = y; j < y + len; ++j)
+					if (max_left < qual[j]) max_left = qual[j];
+				if ((cigar[k+1]&0xf) == BAM_CINS) y += cigar[k+1]>>4;
+				else x += cigar[k+1]>>4;
+				op = cigar[k+2]&0xf; len = cigar[k+2]>>4;
+				for (j = y; j < y + len; ++j) {
+					if (max_rght < qual[j]) max_rght = qual[j];
+					if (qual[j] > BAM2BCF_INDELREG_THRES && indelreg == 0)
+						indelreg = j - y + 1;
+				}
+				if (r->indelreg > indelreg) r->indelreg = indelreg;
+			} else {
+				for (j = y; j <= p->qpos; ++j)
+					if (max_left < qual[j]) max_left = qual[j];
+				for (j = p->qpos + 1; j < y + len; ++j)
+					if (max_rght < qual[j]) max_rght = qual[j];
+					
+			}
+			indelQ = max_left < max_rght? max_left : max_rght;
+			// estimate the sequencing error rate
+			seqQ = bca->openQ;
+			if (p->indel != 0) seqQ += bca->extQ * (abs(p->indel) - 1); // FIXME: better to model homopolymer
+			if (p->indel > 0) {
+				++n_ins; r->ins_len += p->indel;
+			} else if (p->indel < 0) {
+				++n_del; r->del_len += -p->indel;
+			}
+			if (p->indel != 0) { // a different model for tandem repeats
+				uint8_t *seq = bam1_seq(p->b);
+				int tandemQ, qb = bam1_seqi(seq, p->qpos), l;
+				for (j = p->qpos + 1; j < c->l_qseq; ++j)
+					if (qb != bam1_seqi(seq, j)) break;
+				l = j;
+				for (j = (int)p->qpos - 1; j >= 0; --j)
+					if (qb != bam1_seqi(seq, j)) break;
+				l = l - (j + 1);
+				tandemQ = (int)((double)(abs(p->indel)) / l * bca->tandemQ + .499);
+				if (seqQ > tandemQ) seqQ = tandemQ;
+			}
+//			fprintf(stderr, "%s\t%d\t%d\t%d\t%d\t%d\t%d\n", bam1_qname(p->b), pos+1, p->indel, indelQ, seqQ, max_left, max_rght);
+			if (indelQ > seqQ) indelQ = seqQ;
+			q = indelQ;
+		}
+		if (q < bca->min_baseQ) continue;
+		mapQ = p->b->core.qual < bca->capQ? p->b->core.qual : bca->capQ;
+		if (q > mapQ) q = mapQ;
+		if (q > 63) q = 63;
+		if (q < 4) q = 4;
+		b = p->indel? 1 : 0;
+		bca->bases[n++] = q<<5 | (int)bam1_strand(p->b)<<4 | b;
+		// collect annotations
+		r->qsum[b] += q;
+		is_diff = b;
+		++r->anno[0<<2|is_diff<<1|bam1_strand(p->b)];
+		min_dist = p->b->core.l_qseq - 1 - p->qpos;
+		if (min_dist > p->qpos) min_dist = p->qpos;
+		if (min_dist > CAP_DIST) min_dist = CAP_DIST;
+		r->anno[1<<2|is_diff<<1|0] += indelQ;
+		r->anno[1<<2|is_diff<<1|1] += indelQ * indelQ;
+		r->anno[2<<2|is_diff<<1|0] += mapQ;
+		r->anno[2<<2|is_diff<<1|1] += mapQ * mapQ;
+		r->anno[3<<2|is_diff<<1|0] += min_dist;
+		r->anno[3<<2|is_diff<<1|1] += min_dist * min_dist;
+	}
+	r->depth = n;
+	r->ins_len = n_ins? r->ins_len / n_ins : 0;
+	r->del_len = n_del? r->del_len / n_del : 0;
+	if (r->indelreg >= 10000) r->indelreg = 0;
+	// glfgen
+	errmod_cal(bca->e, n, 2, bca->bases, r->p);
+	return r->depth;	
+}
+
 int bcf_call_combine(int n, const bcf_callret1_t *calls, int ref_base /*4-bit*/, bcf_call_t *call)
 {
 	int ref4, i, j, qsum[4];
 	int64_t tmp;
 	call->ori_ref = ref4 = bam_nt16_nt4_table[ref_base];
+	call->ins_len = call->del_len = 0; call->indelreg = 0;
 	if (ref4 > 4) ref4 = 4;
 	// calculate qsum
 	memset(qsum, 0, 4 * sizeof(int));
@@ -154,19 +264,88 @@ int bcf_call_combine(int n, const bcf_callret1_t *calls, int ref_base /*4-bit*/,
 	return 0;
 }
 
-int bcf_call2bcf(int tid, int pos, bcf_call_t *bc, bcf1_t *b)
+int bcf_call_combine_gap(int n, const bcf_callret1_t *calls, bcf_call_t *call)
 {
+	int i, j, n_ins, n_del;
+	// combine annotations
+	call->ori_ref = 4;
+	memset(call->anno, 0, 16 * sizeof(int));
+	call->ins_len = call->del_len = 0; call->indelreg = 10000;
+	for (i = call->depth = 0, n_ins = n_del = 0; i < n; ++i) {
+		const bcf_callret1_t *r = calls + i;
+		if (r->depth > 0) {
+			call->depth += r->depth;
+			if (r->ins_len > 0) {
+				call->ins_len += r->ins_len;
+				++n_ins;
+			}
+			if (r->del_len > 0) {
+				call->del_len += r->del_len;
+				++n_del;
+			}
+			if (r->indelreg > 0 && call->indelreg > r->indelreg)
+				call->indelreg = r->indelreg;
+			for (j = 0; j < 16; ++j) call->anno[j] += r->anno[j];
+		}
+	}
+	if (call->depth == 0) return 0; // no indels
+	call->ins_len = n_ins? call->ins_len / n_ins : 0;
+	call->del_len = n_del? call->del_len / n_del : 0;
+	//
+	for (i = 0; i < 5; ++i) call->a[i] = -1;
+	call->a[0] = 0; call->a[1] = 1;
+	call->unseen = -1;
+	call->n_alleles = 2;
+	// set the PL array
+	if (call->n < n) {
+		call->n = n;
+		call->PL = realloc(call->PL, 15 * n);
+	}
+	{
+		int g[3];
+		double sum_min = 0.;
+		g[0] = 0; g[1] = 1; g[2] = 3;
+		for (i = 0; i < n; ++i) {
+			uint8_t *PL = call->PL + 3 * i;
+			const bcf_callret1_t *r = calls + i;
+			float min = 1e37;
+			for (j = 0; j < 3; ++j)
+				if (min > r->p[g[j]]) min = r->p[g[j]];
+			sum_min += min;
+			for (j = 0; j < 3; ++j) {
+				int y;
+				y = (int)(r->p[g[j]] - min + .499);
+				if (y > 255) y = 255;
+				PL[j] = y;
+			}
+		}
+		call->shift = (int)(sum_min + .499);
+	}
+	return 0;
+}
+
+int bcf_call2bcf(int tid, int pos, bcf_call_t *bc, bcf1_t *b, bcf_callret1_t *bcr, int is_SP)
+{
+	extern double kt_fisher_exact(int n11, int n12, int n21, int n22, double *_left, double *_right, double *two);
 	kstring_t s;
 	int i;
 	b->n_smpl = bc->n;
 	b->tid = tid; b->pos = pos; b->qual = 0;
 	s.s = b->str; s.m = b->m_str; s.l = 0;
 	kputc('\0', &s);
-	kputc("ACGTN"[bc->ori_ref], &s); kputc('\0', &s);
-	for (i = 1; i < 5; ++i) {
-		if (bc->a[i] < 0) break;
-		if (i > 1) kputc(',', &s);
-		kputc(bc->unseen == i? 'X' : "ACGT"[bc->a[i]], &s);
+	if (bc->ins_len > 0 || bc->del_len > 0) { // an indel
+		for (i = 0; i < bc->indelreg; ++i) kputc('N', &s);
+		kputc('\0', &s);
+		if (bc->ins_len > 0 && bc->del_len > 0) kputs("<INDEL>", &s);
+		else if (bc->ins_len > 0) kputs("<INS>", &s);
+		else if (bc->del_len > 0) kputs("<DEL>", &s);
+	} else { // SNP
+		kputc("ACGTN"[bc->ori_ref], &s); kputc('\0', &s);
+		for (i = 1; i < 5; ++i) {
+			if (bc->a[i] < 0) break;
+			if (i > 1) kputc(',', &s);
+			kputc(bc->unseen == i? 'X' : "ACGT"[bc->a[i]], &s);
+		}
 	}
 	kputc('\0', &s);
 	kputc('\0', &s);
@@ -178,9 +357,36 @@ int bcf_call2bcf(int tid, int pos, bcf_call_t *bc, bcf1_t *b)
 	}
 	kputc('\0', &s);
 	// FMT
-	kputs("PL", &s); kputc('\0', &s);
+	kputs("PL", &s);
+	if (bcr) {
+		kputs(":DP", &s);
+		if (is_SP) kputs(":SP", &s);
+	}
+	kputc('\0', &s);
 	b->m_str = s.m; b->str = s.s; b->l_str = s.l;
 	bcf_sync(b);
 	memcpy(b->gi[0].data, bc->PL, b->gi[0].len * bc->n);
+	if (bcr) {
+		uint16_t *dp = (uint16_t*)b->gi[1].data;
+		uint8_t *sp = is_SP? b->gi[2].data : 0;
+		for (i = 0; i < bc->n; ++i) {
+			bcf_callret1_t *p = bcr + i;
+			dp[i] = p->depth < 0xffff? p->depth : 0xffff;
+			if (is_SP) {
+				if (p->anno[0] + p->anno[1] < 2 || p->anno[2] + p->anno[3] < 2
+					|| p->anno[0] + p->anno[2] < 2 || p->anno[1] + p->anno[3] < 2)
+				{
+					sp[i] = 0;
+				} else {
+					double left, right, two;
+					int x;
+					kt_fisher_exact(p->anno[0], p->anno[1], p->anno[2], p->anno[3], &left, &right, &two);
+					x = (int)(-4.343 * log(two) + .499);
+					if (x > 255) x = 255;
+					sp[i] = x;
+				}
+			}
+		}
+	}
 	return 0;
 }