adding support for SAM/BAM output using htslib. Please turn on within

the Makefile.

Makefile

@@ -2,30 +2,44 @@ CC=			gcc
 #CC=			clang --analyze
 CFLAGS=		-g -Wall -Wno-unused-function -O2
 WRAP_MALLOC=-DUSE_MALLOC_WRAPPERS
+# set to 1 if you wish to have bam support, type 'make clean; make all'
+USE_HTSLIB=0
 AR=			ar
-DFLAGS=		-DHAVE_PTHREAD $(WRAP_MALLOC)
+DFLAGS=		-DHAVE_PTHREAD $(WRAP_MALLOC) 
 LOBJS=		utils.o kthread.o kstring.o ksw.o bwt.o bntseq.o bwa.o bwamem.o bwamem_pair.o bwamem_extra.o malloc_wrap.o
 AOBJS=		QSufSort.o bwt_gen.o bwase.o bwaseqio.o bwtgap.o bwtaln.o bamlite.o \
 			is.o bwtindex.o bwape.o kopen.o pemerge.o \
 			bwtsw2_core.o bwtsw2_main.o bwtsw2_aux.o bwt_lite.o \
 			bwtsw2_chain.o fastmap.o bwtsw2_pair.o
 PROG=		bwa
 INCLUDES=	
-LIBS=		-lm -lz -lpthread
+LIBS=		-lm -lz -lpthread 
 SUBDIRS=	.
 
 .SUFFIXES:.c .o .cc
 
 .c.o:
-		$(CC) -c $(CFLAGS) $(DFLAGS) $(INCLUDES) $< -o $@
+ifeq ($(USE_HTSLIB),1)
+	$(CC) -c $(CFLAGS) $(DFLAGS) -DUSE_HTSLIB $(INCLUDES) -I ../htslib $< -o $@
+else
+	$(CC) -c $(CFLAGS) $(DFLAGS) $(INCLUDES) $< -o $@
+endif
 
 all:$(PROG)
 
 bwa:libbwa.a $(AOBJS) main.o
-		$(CC) $(CFLAGS) $(DFLAGS) $(AOBJS) main.o -o $@ -L. -lbwa $(LIBS)
+ifeq ($(USE_HTSLIB),1)
+	$(CC) $(CFLAGS) $(DFLAGS) $(AOBJS) main.o -o $@ ../htslib/libhts.a -L. -L../htslib -lbwa $(LIBS)
+else
+	$(CC) $(CFLAGS) $(DFLAGS) $(AOBJS) main.o -o $@ -L. -lbwa $(LIBS)
+endif
 
 bwamem-lite:libbwa.a example.o
-		$(CC) $(CFLAGS) $(DFLAGS) example.o -o $@ -L. -lbwa $(LIBS)
+ifeq ($(USE_HTSLIB),1)
+	$(CC) $(CFLAGS) $(DFLAGS) example.o -o $@ ../htslib/libhts.a -L. -L../htslib -lbwa $(LIBS)
+else
+	$(CC) $(CFLAGS) $(DFLAGS) example.o -o $@ -L. -lbwa $(LIBS)
+endif
 
 libbwa.a:$(LOBJS)
 		$(AR) -csru $@ $(LOBJS)

bamlite.c

@@ -1,3 +1,4 @@
+#ifndef USE_HTSLIB
 #include <stdlib.h>
 #include <ctype.h>
 #include <string.h>
@@ -208,3 +209,4 @@ int bamlite_gzclose(gzFile file) {
 	return ret;
 }
 #endif /* USE_VERBOSE_ZLIB_WRAPPERS */
+#endif

bamlite.h

@@ -1,5 +1,6 @@
 #ifndef BAMLITE_H_
 #define BAMLITE_H_
+#ifndef USE_HTSLIB
 
 #include <stdint.h>
 #include <zlib.h>
@@ -112,3 +113,4 @@ extern "C" {
 #endif
 
 #endif
+#endif

bwa.c

@@ -7,6 +7,9 @@
 #include "ksw.h"
 #include "utils.h"
 #include "kstring.h"
+#ifdef USE_HTSLIB
+#include <htslib/sam.h>
+#endif
 
 #ifdef USE_MALLOC_WRAPPERS
 #  include "malloc_wrap.h"
@@ -274,6 +277,19 @@ void bwa_print_sam_hdr(const bntseq_t *bns, const char *rg_line)
 	err_printf("%s\n", bwa_pg);
 }
 
+#ifdef USE_HTSLIB
+void bwa_format_sam_hdr(const bntseq_t *bns, const char *rg_line, kstring_t *str)
+{
+	int i;
+	extern char *bwa_pg;
+	str->l = 0; str->s = 0;
+	for (i = 0; i < bns->n_seqs; ++i) 
+		ksprintf(str, "@SQ\tSN:%s\tLN:%d\n", bns->anns[i].name, bns->anns[i].len);
+	if (rg_line) ksprintf(str, "%s\n", rg_line);
+	ksprintf(str, "%s\n", bwa_pg);
+}
+#endif
+
 static char *bwa_escape(char *s)
 {
 	char *p, *q;
@@ -319,3 +335,26 @@ char *bwa_set_rg(const char *s)
 	return 0;
 }
 
+#ifdef USE_HTSLIB
+bams_t *bams_init() {
+	return calloc(1, sizeof(bams_t));
+}
+
+void bams_add(bams_t *bams, bam1_t *b) {
+	if (bams->m == bams->l) {
+		bams->m = bams->m << 2;
+		bams->bams = realloc(bams->bams, sizeof(bam1_t) * bams->m);
+	}
+	bams->bams[bams->l] = b;
+	bams->l++;
+}
+
+void bams_destroy(bams_t *bams) {
+	int i;
+	for (i = 0; i < bams->l; i++) {
+		bam_destroy1(bams->bams[i]);
+	}
+	free(bams->bams);
+	free(bams);
+}
+#endif

bwa.h

@@ -4,6 +4,9 @@
 #include <stdint.h>
 #include "bntseq.h"
 #include "bwt.h"
+#ifdef USE_HTSLIB
+#include <htslib/sam.h>
+#endif
 
 #define BWA_IDX_BWT 0x1
 #define BWA_IDX_BNS 0x2
@@ -16,11 +19,31 @@ typedef struct {
 	uint8_t  *pac; // the actual 2-bit encoded reference sequences with 'N' converted to a random base
 } bwaidx_t;
 
+#ifdef USE_HTSLIB
+typedef struct {
+	int l, m;
+	bam1_t **bams;
+} bams_t;
+#endif
+
 typedef struct {
 	int l_seq;
+#ifdef USE_HTSLIB
+	char *name, *comment, *seq, *qual;
+	bams_t *bams;
+#else
 	char *name, *comment, *seq, *qual, *sam;
+#endif
 } bseq1_t;
 
+// This is here to faciliate passing around HTSLIB's bam_hdr_t structure when we are not compiling with HTSLIB
+#ifndef USE_HTSLIB
+typedef struct {
+	void *ptr;
+} bam_hdr_t; // DO NOT USE
+#endif
+
+
 extern int bwa_verbose;
 extern char bwa_rg_id[256];
 
@@ -41,8 +64,17 @@ extern "C" {
 	void bwa_idx_destroy(bwaidx_t *idx);
 
 	void bwa_print_sam_hdr(const bntseq_t *bns, const char *rg_line);
+#ifdef USE_HTSLIB
+	void bwa_format_sam_hdr(const bntseq_t *bns, const char *rg_line, kstring_t *str);
+#endif
 	char *bwa_set_rg(const char *s);
 
+#ifdef USE_HTSLIB
+	bams_t *bams_init();
+	void bams_add(bams_t *bams, bam1_t *b);
+	void bams_destroy(bams_t *bams);
+#endif
+
 #ifdef __cplusplus
 }
 #endif

bwamem.c

@@ -15,6 +15,10 @@
 #include "ksort.h"
 #include "utils.h"
 
+#ifdef USE_HTSLIB
+#include <htslib/sam.h>
+#endif
+
 #ifdef USE_MALLOC_WRAPPERS
 #  include "malloc_wrap.h"
 #endif
@@ -805,7 +809,7 @@ static inline int get_rlen(int n_cigar, const uint32_t *cigar)
 	return l;
 }
 
-void mem_aln2sam(const bntseq_t *bns, kstring_t *str, bseq1_t *s, int n, const mem_aln_t *list, int which, const mem_aln_t *m_, int softclip_all)
+void mem_aln2sam(const bntseq_t *bns, kstring_t *str, bseq1_t *s, int n, const mem_aln_t *list, int which, const mem_aln_t *m_, int softclip_all, bam_hdr_t *h)
 {
 	int i, l_name;
 	mem_aln_t ptmp = list[which], *p = &ptmp, mtmp, *m = 0; // make a copy of the alignment to convert
@@ -922,6 +926,15 @@ void mem_aln2sam(const bntseq_t *bns, kstring_t *str, bseq1_t *s, int n, const m
 	if (p->XA) { kputsn("\tXA:Z:", 6, str); kputs(p->XA, str); }
 	if (s->comment) { kputc('\t', str); kputs(s->comment, str); }
 	kputc('\n', str);
+
+#ifdef USE_HTSLIB
+	bam1_t *b = bam_init1();
+	if (sam_parse1(str, h, b) < 0) {
+		// TODO: error!
+	}
+	bams_add(s->bams, b);
+	str->l = 0; str->s = 0;
+#endif
 }
 
 /************************
@@ -955,7 +968,7 @@ int mem_approx_mapq_se(const mem_opt_t *opt, const mem_alnreg_t *a)
 }
 
 // TODO (future plan): group hits into a uint64_t[] array. This will be cleaner and more flexible
-void mem_reg2sam_se(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a, int extra_flag, const mem_aln_t *m)
+void mem_reg2sam_se(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a, int extra_flag, const mem_aln_t *m, bam_hdr_t *h)
 {
 	extern char **mem_gen_alt(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, mem_alnreg_v *a, int l_query, const char *query);
 	kstring_t str;
@@ -987,14 +1000,16 @@ void mem_reg2sam_se(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pa
 		mem_aln_t t;
 		t = mem_reg2aln(opt, bns, pac, s->l_seq, s->seq, 0);
 		t.flag |= extra_flag;
-		mem_aln2sam(bns, &str, s, 1, &t, 0, m, opt->flag&MEM_F_SOFTCLIP);
+		mem_aln2sam(bns, &str, s, 1, &t, 0, m, opt->flag&MEM_F_SOFTCLIP, h);
 	} else {
 		for (k = 0; k < aa.n; ++k)
-			mem_aln2sam(bns, &str, s, aa.n, aa.a, k, m, opt->flag&MEM_F_SOFTCLIP);
+			mem_aln2sam(bns, &str, s, aa.n, aa.a, k, m, opt->flag&MEM_F_SOFTCLIP, h);
 		for (k = 0; k < aa.n; ++k) free(aa.a[k].cigar);
 		free(aa.a);
 	}
+#ifndef USE_HTSLIB
 	s->sam = str.s;
+#endif
 	if (XA) {
 		for (k = 0; k < a->n; ++k) free(XA[k]);
 		free(XA);
@@ -1120,6 +1135,7 @@ typedef struct {
 	bseq1_t *seqs;
 	mem_alnreg_v *regs;
 	int64_t n_processed;
+	bam_hdr_t *h;
 } worker_t;
 
 static void worker1(void *data, int i, int tid)
@@ -1138,26 +1154,33 @@ static void worker1(void *data, int i, int tid)
 
 static void worker2(void *data, int i, int tid)
 {
-	extern int mem_sam_pe(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, const mem_pestat_t pes[4], uint64_t id, bseq1_t s[2], mem_alnreg_v a[2]);
+	extern int mem_sam_pe(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, const mem_pestat_t pes[4], uint64_t id, bseq1_t s[2], mem_alnreg_v a[2], bam_hdr_t *h);
 	extern void mem_reg2ovlp(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a);
 	worker_t *w = (worker_t*)data;
 	if (!(w->opt->flag&MEM_F_PE)) {
+#ifdef USE_HTSLIB
+		w->seqs[i].bams = bams_init();
+#endif
 		if (bwa_verbose >= 4) printf("=====> Finalizing read '%s' <=====\n", w->seqs[i].name);
 		if (w->opt->flag & MEM_F_ALN_REG) {
 			mem_reg2ovlp(w->opt, w->bns, w->pac, &w->seqs[i], &w->regs[i]);
 		} else {
 			mem_mark_primary_se(w->opt, w->regs[i].n, w->regs[i].a, w->n_processed + i);
-			mem_reg2sam_se(w->opt, w->bns, w->pac, &w->seqs[i], &w->regs[i], 0, 0);
+			mem_reg2sam_se(w->opt, w->bns, w->pac, &w->seqs[i], &w->regs[i], 0, 0, w->h);
 		}
 		free(w->regs[i].a);
 	} else {
 		if (bwa_verbose >= 4) printf("=====> Finalizing read pair '%s' <=====\n", w->seqs[i<<1|0].name);
-		mem_sam_pe(w->opt, w->bns, w->pac, w->pes, (w->n_processed>>1) + i, &w->seqs[i<<1], &w->regs[i<<1]);
+#ifdef USE_HTSLIB
+		w->seqs[i<<1].bams = bams_init();
+		w->seqs[1+(i<<1)].bams = bams_init();
+#endif
+		mem_sam_pe(w->opt, w->bns, w->pac, w->pes, (w->n_processed>>1) + i, &w->seqs[i<<1], &w->regs[i<<1], w->h);
 		free(w->regs[i<<1|0].a); free(w->regs[i<<1|1].a);
 	}
 }
 
-void mem_process_seqs(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *bns, const uint8_t *pac, int64_t n_processed, int n, bseq1_t *seqs, const mem_pestat_t *pes0)
+void mem_process_seqs(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *bns, const uint8_t *pac, int64_t n_processed, int n, bseq1_t *seqs, const mem_pestat_t *pes0, bam_hdr_t *h)
 {
 	extern void kt_for(int n_threads, void (*func)(void*,int,int), void *data, int n);
 	worker_t w;
@@ -1169,12 +1192,13 @@ void mem_process_seqs(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *bn
 	ctime = cputime(); rtime = realtime();
 	global_bns = bns;
 	regs = malloc(n * sizeof(mem_alnreg_v));
-	w.opt = opt; w.bwt = bwt; w.bns = bns; w.pac = pac;
+    w.opt = opt; w.bwt = bwt; w.bns = bns; w.pac = pac;
 	w.seqs = seqs; w.regs = regs; w.n_processed = n_processed;
 	w.pes = &pes[0];
 	w.aux = malloc(opt->n_threads * sizeof(smem_aux_t));
 	for (i = 0; i < opt->n_threads; ++i)
 		w.aux[i] = smem_aux_init();
+	w.h = h;
 	kt_for(opt->n_threads, worker1, &w, (opt->flag&MEM_F_PE)? n>>1 : n); // find mapping positions
 	for (i = 0; i < opt->n_threads; ++i)
 		smem_aux_destroy(w.aux[i]);

bwamem.h

@@ -50,6 +50,9 @@ typedef struct {
 	int max_matesw;         // perform maximally max_matesw rounds of mate-SW for each end
 	int max_hits;           // if there are max_hits or fewer, output them all
 	int8_t mat[25];         // scoring matrix; mat[0] == 0 if unset
+#ifdef USE_HTSLIB
+	int bam_output;         
+#endif
 } mem_opt_t;
 
 typedef struct {
@@ -123,8 +126,9 @@ extern "C" {
 	 * @param seqs   query sequences; $seqs[i].seq/sam to be modified after the call
 	 * @param pes0   insert-size info; if NULL, infer from data; if not NULL, it should be an array with 4 elements,
 	 *               corresponding to each FF, FR, RF and RR orientation. See mem_pestat() for more info.
+	 * @param h      the BAM header, NULL if not using HTSLIB
 	 */
-	void mem_process_seqs(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *bns, const uint8_t *pac, int64_t n_processed, int n, bseq1_t *seqs, const mem_pestat_t *pes0);
+	void mem_process_seqs(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *bns, const uint8_t *pac, int64_t n_processed, int n, bseq1_t *seqs, const mem_pestat_t *pes0, bam_hdr_t *h);
 
 	/**
 	 * Find the aligned regions for one query sequence

bwamem_extra.c

@@ -80,7 +80,11 @@ mem_alnreg_v mem_align1(const mem_opt_t *opt, const bwt_t *bwt, const bntseq_t *
 	return ar;
 }
 
+#ifdef USE_HTSLIB
+void mem_reg2ovlp(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a, bam_hdr_t *h)
+#else
 void mem_reg2ovlp(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac, bseq1_t *s, mem_alnreg_v *a)
+#endif
 {
 	int i;
 	kstring_t str = {0,0,0};
@@ -102,7 +106,15 @@ void mem_reg2ovlp(const mem_opt_t *opt, const bntseq_t *bns, const uint8_t *pac,
 		ksprintf(&str, "%.3f", (double)p->truesc / opt->a / (qe - qb > re - rb? qe - qb : re - rb));
 		kputc('\n', &str);
 	}
+#ifdef USE_HTSLIB
+	bam1_t *b = bam_init1();
+	if (sam_parse1(&str, h, b) < 0) {
+		// TODO: error!
+	}
+	bams_add(s->bams, b);
+#else
 	s->sam = str.s;
+#endif
 }
 
 // Okay, returning strings is bad, but this has happened a lot elsewhere. If I have time, I need serious code cleanup.