diff PsiCLASS-1.0.2/samtools-0.1.19/bam_index.c @ 0:903fc43d6227 draft default tip

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author lsong10
date Fri, 26 Mar 2021 16:52:45 +0000
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--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/PsiCLASS-1.0.2/samtools-0.1.19/bam_index.c	Fri Mar 26 16:52:45 2021 +0000
@@ -0,0 +1,726 @@
+#include <ctype.h>
+#include <assert.h>
+#include "bam.h"
+#include "khash.h"
+#include "ksort.h"
+#include "bam_endian.h"
+#ifdef _USE_KNETFILE
+#include "knetfile.h"
+#endif
+
+/*!
+  @header
+
+  Alignment indexing. Before indexing, BAM must be sorted based on the
+  leftmost coordinate of alignments. In indexing, BAM uses two indices:
+  a UCSC binning index and a simple linear index. The binning index is
+  efficient for alignments spanning long distance, while the auxiliary
+  linear index helps to reduce unnecessary seek calls especially for
+  short alignments.
+
+  The UCSC binning scheme was suggested by Richard Durbin and Lincoln
+  Stein and is explained by Kent et al. (2002). In this scheme, each bin
+  represents a contiguous genomic region which can be fully contained in
+  another bin; each alignment is associated with a bin which represents
+  the smallest region containing the entire alignment. The binning
+  scheme is essentially another representation of R-tree. A distinct bin
+  uniquely corresponds to a distinct internal node in a R-tree. Bin A is
+  a child of Bin B if region A is contained in B.
+
+  In BAM, each bin may span 2^29, 2^26, 2^23, 2^20, 2^17 or 2^14 bp. Bin
+  0 spans a 512Mbp region, bins 1-8 span 64Mbp, 9-72 8Mbp, 73-584 1Mbp,
+  585-4680 128Kbp and bins 4681-37449 span 16Kbp regions. If we want to
+  find the alignments overlapped with a region [rbeg,rend), we need to
+  calculate the list of bins that may be overlapped the region and test
+  the alignments in the bins to confirm the overlaps. If the specified
+  region is short, typically only a few alignments in six bins need to
+  be retrieved. The overlapping alignments can be quickly fetched.
+
+ */
+
+#define BAM_MIN_CHUNK_GAP 32768
+// 1<<14 is the size of minimum bin.
+#define BAM_LIDX_SHIFT    14
+
+#define BAM_MAX_BIN 37450 // =(8^6-1)/7+1
+
+typedef struct {
+	uint64_t u, v;
+} pair64_t;
+
+#define pair64_lt(a,b) ((a).u < (b).u)
+KSORT_INIT(off, pair64_t, pair64_lt)
+
+typedef struct {
+	uint32_t m, n;
+	pair64_t *list;
+} bam_binlist_t;
+
+typedef struct {
+	int32_t n, m;
+	uint64_t *offset;
+} bam_lidx_t;
+
+KHASH_MAP_INIT_INT(i, bam_binlist_t)
+
+struct __bam_index_t {
+	int32_t n;
+	uint64_t n_no_coor; // unmapped reads without coordinate
+	khash_t(i) **index;
+	bam_lidx_t *index2;
+};
+
+// requirement: len <= LEN_MASK
+static inline void insert_offset(khash_t(i) *h, int bin, uint64_t beg, uint64_t end)
+{
+	khint_t k;
+	bam_binlist_t *l;
+	int ret;
+	k = kh_put(i, h, bin, &ret);
+	l = &kh_value(h, k);
+	if (ret) { // not present
+		l->m = 1; l->n = 0;
+		l->list = (pair64_t*)calloc(l->m, 16);
+	}
+	if (l->n == l->m) {
+		l->m <<= 1;
+		l->list = (pair64_t*)realloc(l->list, l->m * 16);
+	}
+	l->list[l->n].u = beg; l->list[l->n++].v = end;
+}
+
+static inline void insert_offset2(bam_lidx_t *index2, bam1_t *b, uint64_t offset)
+{
+	int i, beg, end;
+	beg = b->core.pos >> BAM_LIDX_SHIFT;
+	end = (bam_calend(&b->core, bam1_cigar(b)) - 1) >> BAM_LIDX_SHIFT;
+	if (index2->m < end + 1) {
+		int old_m = index2->m;
+		index2->m = end + 1;
+		kroundup32(index2->m);
+		index2->offset = (uint64_t*)realloc(index2->offset, index2->m * 8);
+		memset(index2->offset + old_m, 0, 8 * (index2->m - old_m));
+	}
+	if (beg == end) {
+		if (index2->offset[beg] == 0) index2->offset[beg] = offset;
+	} else {
+		for (i = beg; i <= end; ++i)
+			if (index2->offset[i] == 0) index2->offset[i] = offset;
+	}
+	index2->n = end + 1;
+}
+
+static void merge_chunks(bam_index_t *idx)
+{
+#if defined(BAM_TRUE_OFFSET) || defined(BAM_VIRTUAL_OFFSET16)
+	khash_t(i) *index;
+	int i, l, m;
+	khint_t k;
+	for (i = 0; i < idx->n; ++i) {
+		index = idx->index[i];
+		for (k = kh_begin(index); k != kh_end(index); ++k) {
+			bam_binlist_t *p;
+			if (!kh_exist(index, k) || kh_key(index, k) == BAM_MAX_BIN) continue;
+			p = &kh_value(index, k);
+			m = 0;
+			for (l = 1; l < p->n; ++l) {
+#ifdef BAM_TRUE_OFFSET
+				if (p->list[m].v + BAM_MIN_CHUNK_GAP > p->list[l].u) p->list[m].v = p->list[l].v;
+#else
+				if (p->list[m].v>>16 == p->list[l].u>>16) p->list[m].v = p->list[l].v;
+#endif
+				else p->list[++m] = p->list[l];
+			} // ~for(l)
+			p->n = m + 1;
+		} // ~for(k)
+	} // ~for(i)
+#endif // defined(BAM_TRUE_OFFSET) || defined(BAM_BGZF)
+}
+
+static void fill_missing(bam_index_t *idx)
+{
+	int i, j;
+	for (i = 0; i < idx->n; ++i) {
+		bam_lidx_t *idx2 = &idx->index2[i];
+		for (j = 1; j < idx2->n; ++j)
+			if (idx2->offset[j] == 0)
+				idx2->offset[j] = idx2->offset[j-1];
+	}
+}
+
+bam_index_t *bam_index_core(bamFile fp)
+{
+	bam1_t *b;
+	bam_header_t *h;
+	int i, ret;
+	bam_index_t *idx;
+	uint32_t last_bin, save_bin;
+	int32_t last_coor, last_tid, save_tid;
+	bam1_core_t *c;
+	uint64_t save_off, last_off, n_mapped, n_unmapped, off_beg, off_end, n_no_coor;
+
+	h = bam_header_read(fp);
+	if(h == 0) {
+	    fprintf(stderr, "[bam_index_core] Invalid BAM header.");
+	    return NULL;
+	}
+
+	idx = (bam_index_t*)calloc(1, sizeof(bam_index_t));
+	b = (bam1_t*)calloc(1, sizeof(bam1_t));
+	c = &b->core;
+
+	idx->n = h->n_targets;
+	bam_header_destroy(h);
+	idx->index = (khash_t(i)**)calloc(idx->n, sizeof(void*));
+	for (i = 0; i < idx->n; ++i) idx->index[i] = kh_init(i);
+	idx->index2 = (bam_lidx_t*)calloc(idx->n, sizeof(bam_lidx_t));
+
+	save_bin = save_tid = last_tid = last_bin = 0xffffffffu;
+	save_off = last_off = bam_tell(fp); last_coor = 0xffffffffu;
+	n_mapped = n_unmapped = n_no_coor = off_end = 0;
+	off_beg = off_end = bam_tell(fp);
+	while ((ret = bam_read1(fp, b)) >= 0) {
+		if (c->tid < 0) ++n_no_coor;
+		if (last_tid < c->tid || (last_tid >= 0 && c->tid < 0)) { // change of chromosomes
+			last_tid = c->tid;
+			last_bin = 0xffffffffu;
+		} else if ((uint32_t)last_tid > (uint32_t)c->tid) {
+			fprintf(stderr, "[bam_index_core] the alignment is not sorted (%s): %d-th chr > %d-th chr\n",
+					bam1_qname(b), last_tid+1, c->tid+1);
+			return NULL;
+		} else if ((int32_t)c->tid >= 0 && last_coor > c->pos) {
+			fprintf(stderr, "[bam_index_core] the alignment is not sorted (%s): %u > %u in %d-th chr\n",
+					bam1_qname(b), last_coor, c->pos, c->tid+1);
+			return NULL;
+		}
+		if (c->tid >= 0 && !(c->flag & BAM_FUNMAP)) insert_offset2(&idx->index2[b->core.tid], b, last_off);
+		if (c->bin != last_bin) { // then possibly write the binning index
+			if (save_bin != 0xffffffffu) // save_bin==0xffffffffu only happens to the first record
+				insert_offset(idx->index[save_tid], save_bin, save_off, last_off);
+			if (last_bin == 0xffffffffu && save_tid != 0xffffffffu) { // write the meta element
+				off_end = last_off;
+				insert_offset(idx->index[save_tid], BAM_MAX_BIN, off_beg, off_end);
+				insert_offset(idx->index[save_tid], BAM_MAX_BIN, n_mapped, n_unmapped);
+				n_mapped = n_unmapped = 0;
+				off_beg = off_end;
+			}
+			save_off = last_off;
+			save_bin = last_bin = c->bin;
+			save_tid = c->tid;
+			if (save_tid < 0) break;
+		}
+		if (bam_tell(fp) <= last_off) {
+			fprintf(stderr, "[bam_index_core] bug in BGZF/RAZF: %llx < %llx\n",
+					(unsigned long long)bam_tell(fp), (unsigned long long)last_off);
+			return NULL;
+		}
+		if (c->flag & BAM_FUNMAP) ++n_unmapped;
+		else ++n_mapped;
+		last_off = bam_tell(fp);
+		last_coor = b->core.pos;
+	}
+	if (save_tid >= 0) {
+		insert_offset(idx->index[save_tid], save_bin, save_off, bam_tell(fp));
+		insert_offset(idx->index[save_tid], BAM_MAX_BIN, off_beg, bam_tell(fp));
+		insert_offset(idx->index[save_tid], BAM_MAX_BIN, n_mapped, n_unmapped);
+	}
+	merge_chunks(idx);
+	fill_missing(idx);
+	if (ret >= 0) {
+		while ((ret = bam_read1(fp, b)) >= 0) {
+			++n_no_coor;
+			if (c->tid >= 0 && n_no_coor) {
+				fprintf(stderr, "[bam_index_core] the alignment is not sorted: reads without coordinates prior to reads with coordinates.\n");
+				return NULL;
+			}
+		}
+	}
+	if (ret < -1) fprintf(stderr, "[bam_index_core] truncated file? Continue anyway. (%d)\n", ret);
+	free(b->data); free(b);
+	idx->n_no_coor = n_no_coor;
+	return idx;
+}
+
+void bam_index_destroy(bam_index_t *idx)
+{
+	khint_t k;
+	int i;
+	if (idx == 0) return;
+	for (i = 0; i < idx->n; ++i) {
+		khash_t(i) *index = idx->index[i];
+		bam_lidx_t *index2 = idx->index2 + i;
+		for (k = kh_begin(index); k != kh_end(index); ++k) {
+			if (kh_exist(index, k))
+				free(kh_value(index, k).list);
+		}
+		kh_destroy(i, index);
+		free(index2->offset);
+	}
+	free(idx->index); free(idx->index2);
+	free(idx);
+}
+
+void bam_index_save(const bam_index_t *idx, FILE *fp)
+{
+	int32_t i, size;
+	khint_t k;
+	fwrite("BAI\1", 1, 4, fp);
+	if (bam_is_be) {
+		uint32_t x = idx->n;
+		fwrite(bam_swap_endian_4p(&x), 4, 1, fp);
+	} else fwrite(&idx->n, 4, 1, fp);
+	for (i = 0; i < idx->n; ++i) {
+		khash_t(i) *index = idx->index[i];
+		bam_lidx_t *index2 = idx->index2 + i;
+		// write binning index
+		size = kh_size(index);
+		if (bam_is_be) { // big endian
+			uint32_t x = size;
+			fwrite(bam_swap_endian_4p(&x), 4, 1, fp);
+		} else fwrite(&size, 4, 1, fp);
+		for (k = kh_begin(index); k != kh_end(index); ++k) {
+			if (kh_exist(index, k)) {
+				bam_binlist_t *p = &kh_value(index, k);
+				if (bam_is_be) { // big endian
+					uint32_t x;
+					x = kh_key(index, k); fwrite(bam_swap_endian_4p(&x), 4, 1, fp);
+					x = p->n; fwrite(bam_swap_endian_4p(&x), 4, 1, fp);
+					for (x = 0; (int)x < p->n; ++x) {
+						bam_swap_endian_8p(&p->list[x].u);
+						bam_swap_endian_8p(&p->list[x].v);
+					}
+					fwrite(p->list, 16, p->n, fp);
+					for (x = 0; (int)x < p->n; ++x) {
+						bam_swap_endian_8p(&p->list[x].u);
+						bam_swap_endian_8p(&p->list[x].v);
+					}
+				} else {
+					fwrite(&kh_key(index, k), 4, 1, fp);
+					fwrite(&p->n, 4, 1, fp);
+					fwrite(p->list, 16, p->n, fp);
+				}
+			}
+		}
+		// write linear index (index2)
+		if (bam_is_be) {
+			int x = index2->n;
+			fwrite(bam_swap_endian_4p(&x), 4, 1, fp);
+		} else fwrite(&index2->n, 4, 1, fp);
+		if (bam_is_be) { // big endian
+			int x;
+			for (x = 0; (int)x < index2->n; ++x)
+				bam_swap_endian_8p(&index2->offset[x]);
+			fwrite(index2->offset, 8, index2->n, fp);
+			for (x = 0; (int)x < index2->n; ++x)
+				bam_swap_endian_8p(&index2->offset[x]);
+		} else fwrite(index2->offset, 8, index2->n, fp);
+	}
+	{ // write the number of reads coor-less records.
+		uint64_t x = idx->n_no_coor;
+		if (bam_is_be) bam_swap_endian_8p(&x);
+		fwrite(&x, 8, 1, fp);
+	}
+	fflush(fp);
+}
+
+static bam_index_t *bam_index_load_core(FILE *fp)
+{
+	int i;
+	char magic[4];
+	bam_index_t *idx;
+	if (fp == 0) {
+		fprintf(stderr, "[bam_index_load_core] fail to load index.\n");
+		return 0;
+	}
+	fread(magic, 1, 4, fp);
+	if (strncmp(magic, "BAI\1", 4)) {
+		fprintf(stderr, "[bam_index_load] wrong magic number.\n");
+		fclose(fp);
+		return 0;
+	}
+	idx = (bam_index_t*)calloc(1, sizeof(bam_index_t));	
+	fread(&idx->n, 4, 1, fp);
+	if (bam_is_be) bam_swap_endian_4p(&idx->n);
+	idx->index = (khash_t(i)**)calloc(idx->n, sizeof(void*));
+	idx->index2 = (bam_lidx_t*)calloc(idx->n, sizeof(bam_lidx_t));
+	for (i = 0; i < idx->n; ++i) {
+		khash_t(i) *index;
+		bam_lidx_t *index2 = idx->index2 + i;
+		uint32_t key, size;
+		khint_t k;
+		int j, ret;
+		bam_binlist_t *p;
+		index = idx->index[i] = kh_init(i);
+		// load binning index
+		fread(&size, 4, 1, fp);
+		if (bam_is_be) bam_swap_endian_4p(&size);
+		for (j = 0; j < (int)size; ++j) {
+			fread(&key, 4, 1, fp);
+			if (bam_is_be) bam_swap_endian_4p(&key);
+			k = kh_put(i, index, key, &ret);
+			p = &kh_value(index, k);
+			fread(&p->n, 4, 1, fp);
+			if (bam_is_be) bam_swap_endian_4p(&p->n);
+			p->m = p->n;
+			p->list = (pair64_t*)malloc(p->m * 16);
+			fread(p->list, 16, p->n, fp);
+			if (bam_is_be) {
+				int x;
+				for (x = 0; x < p->n; ++x) {
+					bam_swap_endian_8p(&p->list[x].u);
+					bam_swap_endian_8p(&p->list[x].v);
+				}
+			}
+		}
+		// load linear index
+		fread(&index2->n, 4, 1, fp);
+		if (bam_is_be) bam_swap_endian_4p(&index2->n);
+		index2->m = index2->n;
+		index2->offset = (uint64_t*)calloc(index2->m, 8);
+		fread(index2->offset, index2->n, 8, fp);
+		if (bam_is_be)
+			for (j = 0; j < index2->n; ++j) bam_swap_endian_8p(&index2->offset[j]);
+	}
+	if (fread(&idx->n_no_coor, 8, 1, fp) == 0) idx->n_no_coor = 0;
+	if (bam_is_be) bam_swap_endian_8p(&idx->n_no_coor);
+	return idx;
+}
+
+bam_index_t *bam_index_load_local(const char *_fn)
+{
+	FILE *fp;
+	char *fnidx, *fn;
+
+	if (strstr(_fn, "ftp://") == _fn || strstr(_fn, "http://") == _fn) {
+		const char *p;
+		int l = strlen(_fn);
+		for (p = _fn + l - 1; p >= _fn; --p)
+			if (*p == '/') break;
+		fn = strdup(p + 1);
+	} else fn = strdup(_fn);
+	fnidx = (char*)calloc(strlen(fn) + 5, 1);
+	strcpy(fnidx, fn); strcat(fnidx, ".bai");
+	fp = fopen(fnidx, "rb");
+	if (fp == 0) { // try "{base}.bai"
+		char *s = strstr(fn, "bam");
+		if (s == fn + strlen(fn) - 3) {
+			strcpy(fnidx, fn);
+			fnidx[strlen(fn)-1] = 'i';
+			fp = fopen(fnidx, "rb");
+		}
+	}
+	free(fnidx); free(fn);
+	if (fp) {
+		bam_index_t *idx = bam_index_load_core(fp);
+		fclose(fp);
+		return idx;
+	} else return 0;
+}
+
+#ifdef _USE_KNETFILE
+static void download_from_remote(const char *url)
+{
+	const int buf_size = 1 * 1024 * 1024;
+	char *fn;
+	FILE *fp;
+	uint8_t *buf;
+	knetFile *fp_remote;
+	int l;
+	if (strstr(url, "ftp://") != url && strstr(url, "http://") != url) return;
+	l = strlen(url);
+	for (fn = (char*)url + l - 1; fn >= url; --fn)
+		if (*fn == '/') break;
+	++fn; // fn now points to the file name
+	fp_remote = knet_open(url, "r");
+	if (fp_remote == 0) {
+		fprintf(stderr, "[download_from_remote] fail to open remote file.\n");
+		return;
+	}
+	if ((fp = fopen(fn, "wb")) == 0) {
+		fprintf(stderr, "[download_from_remote] fail to create file in the working directory.\n");
+		knet_close(fp_remote);
+		return;
+	}
+	buf = (uint8_t*)calloc(buf_size, 1);
+	while ((l = knet_read(fp_remote, buf, buf_size)) != 0)
+		fwrite(buf, 1, l, fp);
+	free(buf);
+	fclose(fp);
+	knet_close(fp_remote);
+}
+#else
+static void download_from_remote(const char *url)
+{
+	return;
+}
+#endif
+
+bam_index_t *bam_index_load(const char *fn)
+{
+	bam_index_t *idx;
+	idx = bam_index_load_local(fn);
+	if (idx == 0 && (strstr(fn, "ftp://") == fn || strstr(fn, "http://") == fn)) {
+		char *fnidx = calloc(strlen(fn) + 5, 1);
+		strcat(strcpy(fnidx, fn), ".bai");
+		fprintf(stderr, "[bam_index_load] attempting to download the remote index file.\n");
+		download_from_remote(fnidx);
+        free(fnidx);
+		idx = bam_index_load_local(fn);
+	}
+	if (idx == 0) fprintf(stderr, "[bam_index_load] fail to load BAM index.\n");
+	return idx;
+}
+
+int bam_index_build2(const char *fn, const char *_fnidx)
+{
+	char *fnidx;
+	FILE *fpidx;
+	bamFile fp;
+	bam_index_t *idx;
+	if ((fp = bam_open(fn, "r")) == 0) {
+		fprintf(stderr, "[bam_index_build2] fail to open the BAM file.\n");
+		return -1;
+	}
+	idx = bam_index_core(fp);
+	bam_close(fp);
+	if(idx == 0) {
+		fprintf(stderr, "[bam_index_build2] fail to index the BAM file.\n");
+		return -1;
+	}
+	if (_fnidx == 0) {
+		fnidx = (char*)calloc(strlen(fn) + 5, 1);
+		strcpy(fnidx, fn); strcat(fnidx, ".bai");
+	} else fnidx = strdup(_fnidx);
+	fpidx = fopen(fnidx, "wb");
+	if (fpidx == 0) {
+		fprintf(stderr, "[bam_index_build2] fail to create the index file.\n");
+		free(fnidx);
+        bam_index_destroy(idx);
+		return -1;
+	}
+	bam_index_save(idx, fpidx);
+	bam_index_destroy(idx);
+	fclose(fpidx);
+	free(fnidx);
+	return 0;
+}
+
+int bam_index_build(const char *fn)
+{
+	return bam_index_build2(fn, 0);
+}
+
+int bam_index(int argc, char *argv[])
+{
+	if (argc < 2) {
+		fprintf(stderr, "Usage: samtools index <in.bam> [out.index]\n");
+		return 1;
+	}
+	if (argc >= 3) bam_index_build2(argv[1], argv[2]);
+	else bam_index_build(argv[1]);
+	return 0;
+}
+
+int bam_idxstats(int argc, char *argv[])
+{
+	bam_index_t *idx;
+	bam_header_t *header;
+	bamFile fp;
+	int i;
+	if (argc < 2) {
+		fprintf(stderr, "Usage: samtools idxstats <in.bam>\n");
+		return 1;
+	}
+	fp = bam_open(argv[1], "r");
+	if (fp == 0) { fprintf(stderr, "[%s] fail to open BAM.\n", __func__); return 1; }
+	header = bam_header_read(fp);
+	bam_close(fp);
+	idx = bam_index_load(argv[1]);
+	if (idx == 0) { fprintf(stderr, "[%s] fail to load the index.\n", __func__); return 1; }
+	for (i = 0; i < idx->n; ++i) {
+		khint_t k;
+		khash_t(i) *h = idx->index[i];
+		printf("%s\t%d", header->target_name[i], header->target_len[i]);
+		k = kh_get(i, h, BAM_MAX_BIN);
+		if (k != kh_end(h))
+			printf("\t%llu\t%llu", (long long)kh_val(h, k).list[1].u, (long long)kh_val(h, k).list[1].v);
+		else printf("\t0\t0");
+		putchar('\n');
+	}
+	printf("*\t0\t0\t%llu\n", (long long)idx->n_no_coor);
+	bam_header_destroy(header);
+	bam_index_destroy(idx);
+	return 0;
+}
+
+static inline int reg2bins(uint32_t beg, uint32_t end, uint16_t list[BAM_MAX_BIN])
+{
+	int i = 0, k;
+	if (beg >= end) return 0;
+	if (end >= 1u<<29) end = 1u<<29;
+	--end;
+	list[i++] = 0;
+	for (k =    1 + (beg>>26); k <=    1 + (end>>26); ++k) list[i++] = k;
+	for (k =    9 + (beg>>23); k <=    9 + (end>>23); ++k) list[i++] = k;
+	for (k =   73 + (beg>>20); k <=   73 + (end>>20); ++k) list[i++] = k;
+	for (k =  585 + (beg>>17); k <=  585 + (end>>17); ++k) list[i++] = k;
+	for (k = 4681 + (beg>>14); k <= 4681 + (end>>14); ++k) list[i++] = k;
+	return i;
+}
+
+static inline int is_overlap(uint32_t beg, uint32_t end, const bam1_t *b)
+{
+	uint32_t rbeg = b->core.pos;
+	uint32_t rend = b->core.n_cigar? bam_calend(&b->core, bam1_cigar(b)) : b->core.pos + 1;
+	return (rend > beg && rbeg < end);
+}
+
+struct __bam_iter_t {
+	int from_first; // read from the first record; no random access
+	int tid, beg, end, n_off, i, finished;
+	uint64_t curr_off;
+	pair64_t *off;
+};
+
+// bam_fetch helper function retrieves 
+bam_iter_t bam_iter_query(const bam_index_t *idx, int tid, int beg, int end)
+{
+	uint16_t *bins;
+	int i, n_bins, n_off;
+	pair64_t *off;
+	khint_t k;
+	khash_t(i) *index;
+	uint64_t min_off;
+	bam_iter_t iter = 0;
+
+	if (beg < 0) beg = 0;
+	if (end < beg) return 0;
+	// initialize iter
+	iter = calloc(1, sizeof(struct __bam_iter_t));
+	iter->tid = tid, iter->beg = beg, iter->end = end; iter->i = -1;
+	//
+	bins = (uint16_t*)calloc(BAM_MAX_BIN, 2);
+	n_bins = reg2bins(beg, end, bins);
+	index = idx->index[tid];
+	if (idx->index2[tid].n > 0) {
+		min_off = (beg>>BAM_LIDX_SHIFT >= idx->index2[tid].n)? idx->index2[tid].offset[idx->index2[tid].n-1]
+			: idx->index2[tid].offset[beg>>BAM_LIDX_SHIFT];
+		if (min_off == 0) { // improvement for index files built by tabix prior to 0.1.4
+			int n = beg>>BAM_LIDX_SHIFT;
+			if (n > idx->index2[tid].n) n = idx->index2[tid].n;
+			for (i = n - 1; i >= 0; --i)
+				if (idx->index2[tid].offset[i] != 0) break;
+			if (i >= 0) min_off = idx->index2[tid].offset[i];
+		}
+	} else min_off = 0; // tabix 0.1.2 may produce such index files
+	for (i = n_off = 0; i < n_bins; ++i) {
+		if ((k = kh_get(i, index, bins[i])) != kh_end(index))
+			n_off += kh_value(index, k).n;
+	}
+	if (n_off == 0) {
+		free(bins); return iter;
+	}
+	off = (pair64_t*)calloc(n_off, 16);
+	for (i = n_off = 0; i < n_bins; ++i) {
+		if ((k = kh_get(i, index, bins[i])) != kh_end(index)) {
+			int j;
+			bam_binlist_t *p = &kh_value(index, k);
+			for (j = 0; j < p->n; ++j)
+				if (p->list[j].v > min_off) off[n_off++] = p->list[j];
+		}
+	}
+	free(bins);
+	if (n_off == 0) {
+		free(off); return iter;
+	}
+	{
+		bam1_t *b = (bam1_t*)calloc(1, sizeof(bam1_t));
+		int l;
+		ks_introsort(off, n_off, off);
+		// resolve completely contained adjacent blocks
+		for (i = 1, l = 0; i < n_off; ++i)
+			if (off[l].v < off[i].v)
+				off[++l] = off[i];
+		n_off = l + 1;
+		// resolve overlaps between adjacent blocks; this may happen due to the merge in indexing
+		for (i = 1; i < n_off; ++i)
+			if (off[i-1].v >= off[i].u) off[i-1].v = off[i].u;
+		{ // merge adjacent blocks
+#if defined(BAM_TRUE_OFFSET) || defined(BAM_VIRTUAL_OFFSET16)
+			for (i = 1, l = 0; i < n_off; ++i) {
+#ifdef BAM_TRUE_OFFSET
+				if (off[l].v + BAM_MIN_CHUNK_GAP > off[i].u) off[l].v = off[i].v;
+#else
+				if (off[l].v>>16 == off[i].u>>16) off[l].v = off[i].v;
+#endif
+				else off[++l] = off[i];
+			}
+			n_off = l + 1;
+#endif
+		}
+		bam_destroy1(b);
+	}
+	iter->n_off = n_off; iter->off = off;
+	return iter;
+}
+
+pair64_t *get_chunk_coordinates(const bam_index_t *idx, int tid, int beg, int end, int *cnt_off)
+{ // for pysam compatibility
+	bam_iter_t iter;
+	pair64_t *off;
+	iter = bam_iter_query(idx, tid, beg, end);
+	off = iter->off; *cnt_off = iter->n_off;
+	free(iter);
+	return off;
+}
+
+void bam_iter_destroy(bam_iter_t iter)
+{
+	if (iter) { free(iter->off); free(iter); }
+}
+
+int bam_iter_read(bamFile fp, bam_iter_t iter, bam1_t *b)
+{
+	int ret;
+	if (iter && iter->finished) return -1;
+	if (iter == 0 || iter->from_first) {
+		ret = bam_read1(fp, b);
+		if (ret < 0 && iter) iter->finished = 1;
+		return ret;
+	}
+	if (iter->off == 0) return -1;
+	for (;;) {
+		if (iter->curr_off == 0 || iter->curr_off >= iter->off[iter->i].v) { // then jump to the next chunk
+			if (iter->i == iter->n_off - 1) { ret = -1; break; } // no more chunks
+			if (iter->i >= 0) assert(iter->curr_off == iter->off[iter->i].v); // otherwise bug
+			if (iter->i < 0 || iter->off[iter->i].v != iter->off[iter->i+1].u) { // not adjacent chunks; then seek
+				bam_seek(fp, iter->off[iter->i+1].u, SEEK_SET);
+				iter->curr_off = bam_tell(fp);
+			}
+			++iter->i;
+		}
+		if ((ret = bam_read1(fp, b)) >= 0) {
+			iter->curr_off = bam_tell(fp);
+			if (b->core.tid != iter->tid || b->core.pos >= iter->end) { // no need to proceed
+				ret = bam_validate1(NULL, b)? -1 : -5; // determine whether end of region or error
+				break;
+			}
+			else if (is_overlap(iter->beg, iter->end, b)) return ret;
+		} else break; // end of file or error
+	}
+	iter->finished = 1;
+	return ret;
+}
+
+int bam_fetch(bamFile fp, const bam_index_t *idx, int tid, int beg, int end, void *data, bam_fetch_f func)
+{
+	int ret;
+	bam_iter_t iter;
+	bam1_t *b;
+	b = bam_init1();
+	iter = bam_iter_query(idx, tid, beg, end);
+	while ((ret = bam_iter_read(fp, iter, b)) >= 0) func(b, data);
+	bam_iter_destroy(iter);
+	bam_destroy1(b);
+	return (ret == -1)? 0 : ret;
+}