Imported Upstream version 0.1.13
[samtools.git] / phase.c
diff --git a/phase.c b/phase.c
new file mode 100644 (file)
index 0000000..ef4eff9
--- /dev/null
+++ b/phase.c
@@ -0,0 +1,687 @@
+#include <stdio.h>
+#include <stdlib.h>
+#include <unistd.h>
+#include <stdint.h>
+#include <math.h>
+#include <zlib.h>
+#include "bam.h"
+#include "errmod.h"
+
+#include "kseq.h"
+KSTREAM_INIT(gzFile, gzread, 16384)
+
+#define MAX_VARS 256
+#define FLIP_PENALTY 2
+#define FLIP_THRES 4
+#define MASK_THRES 3
+
+#define FLAG_FIX_CHIMERA 0x1
+#define FLAG_LIST_EXCL   0x4
+#define FLAG_DROP_AMBI   0x8
+
+typedef struct {
+       // configurations, initialized in the main function
+       int flag, k, min_baseQ, min_varLOD, max_depth;
+       // other global variables
+       int vpos_shift;
+       bamFile fp;
+       char *pre;
+       bamFile out[3];
+       // alignment queue
+       int n, m;
+       bam1_t **b;
+} phaseg_t;
+
+typedef struct {
+       int8_t seq[MAX_VARS]; // TODO: change to dynamic memory allocation!
+       int vpos, beg, end;
+       uint32_t vlen:16, single:1, flip:1, phase:1, phased:1, ambig:1;
+       uint32_t in:16, out:16; // in-phase and out-phase
+} frag_t, *frag_p;
+
+#define rseq_lt(a,b) ((a)->vpos < (b)->vpos)
+
+#include "khash.h"
+KHASH_SET_INIT_INT64(set64)
+KHASH_MAP_INIT_INT64(64, frag_t)
+
+typedef khash_t(64) nseq_t;
+
+#include "ksort.h"
+KSORT_INIT(rseq, frag_p, rseq_lt)
+
+static char nt16_nt4_table[] = { 4, 0, 1, 4, 2, 4, 4, 4, 3, 4, 4, 4, 4, 4, 4, 4 };
+
+static inline uint64_t X31_hash_string(const char *s)
+{
+       uint64_t h = *s;
+       if (h) for (++s ; *s; ++s) h = (h << 5) - h + *s;
+       return h;
+}
+
+static void count1(int l, const uint8_t *seq, int *cnt)
+{
+       int i, j, n_ambi;
+       uint32_t z, x;
+       if (seq[l-1] == 0) return; // do nothing is the last base is ambiguous
+       for (i = n_ambi = 0; i < l; ++i) // collect ambiguous bases
+               if (seq[i] == 0) ++n_ambi;
+       if (l - n_ambi <= 1) return; // only one SNP
+       for (x = 0; x < 1u<<n_ambi; ++x) { // count
+               for (i = j = 0, z = 0; i < l; ++i) {
+                       int c;
+                       if (seq[i]) c = seq[i] - 1;
+                       else {
+                               c = x>>j&1;
+                               ++j;
+                       }
+                       z = z<<1 | c;
+               }
+               ++cnt[z];
+       }
+}
+
+static int **count_all(int l, int vpos, nseq_t *hash)
+{
+       khint_t k;
+       int i, j, **cnt;
+       uint8_t *seq;
+       seq = calloc(l, 1);
+       cnt = calloc(vpos, sizeof(void*));
+       for (i = 0; i < vpos; ++i) cnt[i] = calloc(1<<l, sizeof(int));
+       for (k = 0; k < kh_end(hash); ++k) {
+               if (kh_exist(hash, k)) {
+                       frag_t *f = &kh_val(hash, k);
+                       if (f->vpos >= vpos || f->single) continue; // out of region; or singleton
+                       if (f->vlen == 1) { // such reads should be flagged as deleted previously if everything is right
+                               f->single = 1;
+                               continue;
+                       }
+                       for (j = 1; j < f->vlen; ++j) {
+                               for (i = 0; i < l; ++i)
+                                       seq[i] = j < l - 1 - i? 0 : f->seq[j - (l - 1 - i)];
+                               count1(l, seq, cnt[f->vpos + j]);
+                       }
+               }
+       }
+       free(seq);
+       return cnt;
+}
+
+// phasing
+static int8_t *dynaprog(int l, int vpos, int **w)
+{
+       int *f[2], *curr, *prev, max, i;
+       int8_t **b, *h = 0;
+       uint32_t x, z = 1u<<(l-1), mask = (1u<<l) - 1;
+       f[0] = calloc(z, sizeof(int));
+       f[1] = calloc(z, sizeof(int));
+       b = calloc(vpos, sizeof(void*));
+       prev = f[0]; curr = f[1];
+       // fill the backtrack matrix
+       for (i = 0; i < vpos; ++i) {
+               int *wi = w[i], *tmp;
+               int8_t *bi;
+               bi = b[i] = calloc(z, 1);
+               /* In the following, x is the current state, which is the
+                * lexicographically smaller local haplotype. xc is the complement of
+                * x, or the larger local haplotype; y0 and y1 are the two predecessors
+                * of x. */
+               for (x = 0; x < z; ++x) { // x0 is the smaller 
+                       uint32_t y0, y1, xc;
+                       int c0, c1;
+                       xc = ~x&mask; y0 = x>>1; y1 = xc>>1;
+                       c0 = prev[y0] + wi[x] + wi[xc];
+                       c1 = prev[y1] + wi[x] + wi[xc];
+                       if (c0 > c1) bi[x] = 0, curr[x] = c0;
+                       else bi[x] = 1, curr[x] = c1;
+               }
+               tmp = prev; prev = curr; curr = tmp; // swap
+       }
+       { // backtrack
+               uint32_t max_x = 0;
+               int which = 0;
+               h = calloc(vpos, 1);
+               for (x = 0, max = 0, max_x = 0; x < z; ++x)
+                       if (prev[x] > max) max = prev[x], max_x = x;
+               for (i = vpos - 1, x = max_x; i >= 0; --i) {
+                       h[i] = which? (~x&1) : (x&1);
+                       which = b[i][x]? !which : which;
+                       x = b[i][x]? (~x&mask)>>1 : x>>1;
+               }
+       }
+       // free
+       for (i = 0; i < vpos; ++i) free(b[i]);
+       free(f[0]); free(f[1]); free(b);
+       return h;
+}
+
+// phase each fragment
+static uint64_t *fragphase(int vpos, const int8_t *path, nseq_t *hash, int flip)
+{
+       khint_t k;
+       uint64_t *pcnt;
+       uint32_t *left, *rght, max;
+       left = rght = 0; max = 0;
+       pcnt = calloc(vpos, 8);
+       for (k = 0; k < kh_end(hash); ++k) {
+               if (kh_exist(hash, k)) {
+                       int i, c[2];
+                       frag_t *f = &kh_val(hash, k);
+                       if (f->vpos >= vpos) continue;
+                       // get the phase
+                       c[0] = c[1] = 0;
+                       for (i = 0; i < f->vlen; ++i) {
+                               if (f->seq[i] == 0) continue;
+                               ++c[f->seq[i] == path[f->vpos + i] + 1? 0 : 1];
+                       }
+                       f->phase = c[0] > c[1]? 0 : 1;
+                       f->in = c[f->phase]; f->out = c[1 - f->phase];
+                       f->phased = f->in == f->out? 0 : 1;
+                       f->ambig = (f->in && f->out && f->out < 3 && f->in <= f->out + 1)? 1 : 0;
+                       // fix chimera
+                       f->flip = 0;
+                       if (flip && c[0] >= 3 && c[1] >= 3) {
+                               int sum[2], m, mi, md;
+                               if (f->vlen > max) { // enlarge the array
+                                       max = f->vlen;
+                                       kroundup32(max);
+                                       left = realloc(left, max * 4);
+                                       rght = realloc(rght, max * 4);
+                               }
+                               for (i = 0, sum[0] = sum[1] = 0; i < f->vlen; ++i) { // get left counts
+                                       if (f->seq[i]) {
+                                               int c = f->phase? 2 - f->seq[i] : f->seq[i] - 1;
+                                               ++sum[c == path[f->vpos + i]? 0 : 1];
+                                       }
+                                       left[i] = sum[1]<<16 | sum[0];
+                               }
+                               for (i = f->vlen - 1, sum[0] = sum[1] = 0; i >= 0; --i) { // get right counts
+                                       if (f->seq[i]) {
+                                               int c = f->phase? 2 - f->seq[i] : f->seq[i] - 1;
+                                               ++sum[c == path[f->vpos + i]? 0 : 1];
+                                       }
+                                       rght[i] = sum[1]<<16 | sum[0];
+                               }
+                               // find the best flip point
+                               for (i = m = 0, mi = -1, md = -1; i < f->vlen - 1; ++i) {
+                                       int a[2];
+                                       a[0] = (left[i]&0xffff) + (rght[i+1]>>16&0xffff) - (rght[i+1]&0xffff) * FLIP_PENALTY;
+                                       a[1] = (left[i]>>16&0xffff) + (rght[i+1]&0xffff) - (rght[i+1]>>16&0xffff) * FLIP_PENALTY;
+                                       if (a[0] > a[1]) {
+                                               if (a[0] > m) m = a[0], md = 0, mi = i;
+                                       } else {
+                                               if (a[1] > m) m = a[1], md = 1, mi = i;
+                                       }
+                               }
+                               if (m - c[0] >= FLIP_THRES && m - c[1] >= FLIP_THRES) { // then flip
+                                       f->flip = 1;
+                                       if (md == 0) { // flip the tail
+                                               for (i = mi + 1; i < f->vlen; ++i)
+                                                       if (f->seq[i] == 1) f->seq[i] = 2;
+                                                       else if (f->seq[i] == 2) f->seq[i] = 1;
+                                       } else { // flip the head
+                                               for (i = 0; i <= mi; ++i)
+                                                       if (f->seq[i] == 1) f->seq[i] = 2;
+                                                       else if (f->seq[i] == 2) f->seq[i] = 1;
+                                       }
+                               }
+                       }
+                       // update pcnt[]
+                       if (!f->single) {
+                               for (i = 0; i < f->vlen; ++i) {
+                                       int c;
+                                       if (f->seq[i] == 0) continue;
+                                       c = f->phase? 2 - f->seq[i] : f->seq[i] - 1;
+                                       if (c == path[f->vpos + i]) {
+                                               if (f->phase == 0) ++pcnt[f->vpos + i];
+                                               else pcnt[f->vpos + i] += 1ull<<32;
+                                       } else {
+                                               if (f->phase == 0) pcnt[f->vpos + i] += 1<<16;
+                                               else pcnt[f->vpos + i] += 1ull<<48;
+                                       }
+                               }
+                       }
+               }
+       }
+       free(left); free(rght);
+       return pcnt;
+}
+
+static uint64_t *genmask(int vpos, const uint64_t *pcnt, int *_n)
+{
+       int i, max = 0, max_i = -1, m = 0, n = 0, beg = 0, score = 0;
+       uint64_t *list = 0;
+       for (i = 0; i < vpos; ++i) {
+               uint64_t x = pcnt[i];
+               int c[4], pre = score, s;
+               c[0] = x&0xffff; c[1] = x>>16&0xffff; c[2] = x>>32&0xffff; c[3] = x>>48&0xffff;
+               s = (c[1] + c[3] == 0)? -(c[0] + c[2]) : (c[1] + c[3] - 1);
+               if (c[3] > c[2]) s += c[3] - c[2];
+               if (c[1] > c[0]) s += c[1] - c[0];
+               score += s;
+               if (score < 0) score = 0;
+               if (pre == 0 && score > 0) beg = i; // change from zero to non-zero
+               if ((i == vpos - 1 || score == 0) && max >= MASK_THRES) {
+                       if (n == m) {
+                               m = m? m<<1 : 4;
+                               list = realloc(list, m * 8);
+                       }
+                       list[n++] = (uint64_t)beg<<32 | max_i;
+                       i = max_i; // reset i to max_i
+                       score = 0;
+               } else if (score > max) max = score, max_i = i;
+               if (score == 0) max = 0;
+       }
+       *_n = n;
+       return list;
+}
+
+// trim heading and tailing ambiguous bases; mark deleted and remove sequence
+static int clean_seqs(int vpos, nseq_t *hash)
+{
+       khint_t k;
+       int ret = 0;
+       for (k = 0; k < kh_end(hash); ++k) {
+               if (kh_exist(hash, k)) {
+                       frag_t *f = &kh_val(hash, k);
+                       int beg, end, i;
+                       if (f->vpos >= vpos) {
+                               ret = 1;
+                               continue;
+                       }
+                       for (i = 0; i < f->vlen; ++i)
+                               if (f->seq[i] != 0) break;
+                       beg = i;
+                       for (i = f->vlen - 1; i >= 0; --i)
+                               if (f->seq[i] != 0) break;
+                       end = i + 1;
+                       if (end - beg <= 0) kh_del(64, hash, k);
+                       else {
+                               if (beg != 0) memmove(f->seq, f->seq + beg, end - beg);
+                               f->vpos += beg; f->vlen = end - beg;
+                               f->single = f->vlen == 1? 1 : 0;
+                       }
+               }
+       }
+       return ret;
+}
+
+static void dump_aln(phaseg_t *g, int min_pos, const nseq_t *hash)
+{
+       int i, is_flip, drop_ambi;
+       drop_ambi = g->flag & FLAG_DROP_AMBI;
+       is_flip = (drand48() < 0.5);
+       for (i = 0; i < g->n; ++i) {
+               int end, which;
+               uint64_t key;
+               khint_t k;
+               bam1_t *b = g->b[i];
+               key = X31_hash_string(bam1_qname(b));
+               end = bam_calend(&b->core, bam1_cigar(b));
+               if (end > min_pos) break;
+               k = kh_get(64, hash, key);
+               if (k == kh_end(hash)) which = 3;
+               else {
+                       frag_t *f = &kh_val(hash, k);
+                       if (f->ambig) which = drop_ambi? 2 : 3;
+                       else if (f->phased && f->flip) which = 2;
+                       else if (f->phased == 0) which = 3;
+                       else { // phased and not flipped
+                               char c = 'Y';
+                               which = f->phase;
+                               bam_aux_append(b, "ZP", 'A', 1, (uint8_t*)&c);
+                       }
+                       if (which < 2 && is_flip) which = 1 - which; // increase the randomness
+               }
+               if (which == 3) which = (drand48() < 0.5);
+               bam_write1(g->out[which], b);
+               bam_destroy1(b);
+               g->b[i] = 0;
+       }
+       memmove(g->b, g->b + i, (g->n - i) * sizeof(void*));
+       g->n -= i;
+}
+
+static int phase(phaseg_t *g, const char *chr, int vpos, uint64_t *cns, nseq_t *hash)
+{
+       int i, j, n_seqs = kh_size(hash), n_masked = 0, min_pos;
+       khint_t k;
+       frag_t **seqs;
+       int8_t *path, *sitemask;
+       uint64_t *pcnt, *regmask;
+
+       if (vpos == 0) return 0;
+       i = clean_seqs(vpos, hash); // i is true if hash has an element with its vpos >= vpos
+       min_pos = i? cns[vpos]>>32 : 0x7fffffff;
+       if (vpos == 1) {
+               printf("PS\t%s\t%d\t%d\n", chr, (int)(cns[0]>>32) + 1, (int)(cns[0]>>32) + 1);
+               printf("M0\t%s\t%d\t%d\t%c\t%c\t%d\t0\t0\t0\t0\n//\n", chr, (int)(cns[0]>>32) + 1, (int)(cns[0]>>32) + 1,
+                       "ACGTX"[cns[0]&3], "ACGTX"[cns[0]>>16&3], g->vpos_shift + 1);
+               for (k = 0; k < kh_end(hash); ++k) {
+                       if (kh_exist(hash, k)) {
+                               frag_t *f = &kh_val(hash, k);
+                               if (f->vpos) continue;
+                               f->flip = 0;
+                               if (f->seq[0] == 0) f->phased = 0;
+                               else f->phased = 1, f->phase = f->seq[0] - 1;
+                       }
+               }
+               dump_aln(g, min_pos, hash);
+               ++g->vpos_shift;
+               return 1;
+       }
+       { // phase
+               int **cnt;
+               uint64_t *mask;
+               printf("PS\t%s\t%d\t%d\n", chr, (int)(cns[0]>>32) + 1, (int)(cns[vpos-1]>>32) + 1);
+               sitemask = calloc(vpos, 1);
+               cnt = count_all(g->k, vpos, hash);
+               path = dynaprog(g->k, vpos, cnt);
+               for (i = 0; i < vpos; ++i) free(cnt[i]);
+               free(cnt);
+               pcnt = fragphase(vpos, path, hash, 0); // do not fix chimeras when masking
+               mask = genmask(vpos, pcnt, &n_masked);
+               regmask = calloc(n_masked, 8);
+               for (i = 0; i < n_masked; ++i) {
+                       regmask[i] = cns[mask[i]>>32]>>32<<32 | cns[(uint32_t)mask[i]]>>32;
+                       for (j = mask[i]>>32; j <= (int32_t)mask[i]; ++j)
+                               sitemask[j] = 1;
+               }
+               free(mask);
+               if (g->flag & FLAG_FIX_CHIMERA) {
+                       free(pcnt);
+                       pcnt = fragphase(vpos, path, hash, 1);
+               }
+       }
+       for (i = 0; i < n_masked; ++i)
+               printf("FL\t%s\t%d\t%d\n", chr, (int)(regmask[i]>>32) + 1, (int)regmask[i] + 1);
+       for (i = 0; i < vpos; ++i) {
+               uint64_t x = pcnt[i];
+               int8_t c[2];
+               c[0] = (cns[i]&0xffff)>>2 == 0? 4 : (cns[i]&3);
+               c[1] = (cns[i]>>16&0xffff)>>2 == 0? 4 : (cns[i]>>16&3);
+               printf("M%d\t%s\t%d\t%d\t%c\t%c\t%d\t%d\t%d\t%d\t%d\n", sitemask[i]+1, chr, (int)(cns[0]>>32) + 1, (int)(cns[i]>>32) + 1, "ACGTX"[c[path[i]]], "ACGTX"[c[1-path[i]]],
+                       i + g->vpos_shift + 1, (int)(x&0xffff), (int)(x>>16&0xffff), (int)(x>>32&0xffff), (int)(x>>48&0xffff));
+       }
+       free(path); free(pcnt); free(regmask); free(sitemask);
+       seqs = calloc(n_seqs, sizeof(void*));
+       for (k = 0, i = 0; k < kh_end(hash); ++k) 
+               if (kh_exist(hash, k) && kh_val(hash, k).vpos < vpos && !kh_val(hash, k).single)
+                       seqs[i++] = &kh_val(hash, k);
+       n_seqs = i;
+       ks_introsort_rseq(n_seqs, seqs);
+       for (i = 0; i < n_seqs; ++i) {
+               frag_t *f = seqs[i];
+               printf("EV\t0\t%s\t%d\t40\t%dM\t*\t0\t0\t", chr, f->vpos + 1 + g->vpos_shift, f->vlen);
+               for (j = 0; j < f->vlen; ++j) {
+                       uint32_t c = cns[f->vpos + j];
+                       if (f->seq[j] == 0) putchar('N');
+                       else putchar("ACGT"[f->seq[j] == 1? (c&3) : (c>>16&3)]);
+               }
+               printf("\t*\tYP:i:%d\tYF:i:%d\tYI:i:%d\tYO:i:%d\tYS:i:%d\n", f->phase, f->flip, f->in, f->out, f->beg+1);
+       }
+       free(seqs);
+       printf("//\n");
+       fflush(stdout);
+       g->vpos_shift += vpos;
+       dump_aln(g, min_pos, hash);
+       return vpos;
+}
+
+static void update_vpos(int vpos, nseq_t *hash)
+{
+       khint_t k;
+       for (k = 0; k < kh_end(hash); ++k) {
+               if (kh_exist(hash, k)) {
+                       frag_t *f = &kh_val(hash, k);
+                       if (f->vpos < vpos) kh_del(64, hash, k); // TODO: if frag_t::seq is allocated dynamically, free it
+                       else f->vpos -= vpos;
+               }
+       }
+}
+
+static nseq_t *shrink_hash(nseq_t *hash) // TODO: to implement
+{
+       return hash;
+}
+
+static int readaln(void *data, bam1_t *b)
+{
+       phaseg_t *g = (phaseg_t*)data;
+       int ret;
+       ret = bam_read1(g->fp, b);
+       if (ret < 0) return ret;
+       if (!(b->core.flag & (BAM_FUNMAP|BAM_FSECONDARY|BAM_FQCFAIL|BAM_FDUP)) && g->pre) {
+               if (g->n == g->m) {
+                       g->m = g->m? g->m<<1 : 16;
+                       g->b = realloc(g->b, g->m * sizeof(void*));
+               }
+               g->b[g->n++] = bam_dup1(b);
+       }
+       return ret;
+}
+
+static khash_t(set64) *loadpos(const char *fn, bam_header_t *h)
+{
+       gzFile fp;
+       kstream_t *ks;
+       int ret, dret;
+       kstring_t *str;
+       khash_t(set64) *hash;
+
+       hash = kh_init(set64);
+       str = calloc(1, sizeof(kstring_t));
+       fp = strcmp(fn, "-")? gzopen(fn, "r") : gzdopen(fileno(stdin), "r");
+       ks = ks_init(fp);
+       while (ks_getuntil(ks, 0, str, &dret) >= 0) {
+               int tid = bam_get_tid(h, str->s);
+               if (tid >= 0 && dret != '\n') {
+                       if (ks_getuntil(ks, 0, str, &dret) >= 0) {
+                               uint64_t x = (uint64_t)tid<<32 | (atoi(str->s) - 1);
+                               kh_put(set64, hash, x, &ret);
+                       } else break;
+               }
+               if (dret != '\n') while ((dret = ks_getc(ks)) > 0 && dret != '\n');
+               if (dret < 0) break;
+       }
+       ks_destroy(ks);
+       gzclose(fp);
+       free(str->s); free(str);
+       return hash;
+}
+
+static int gl2cns(float q[16])
+{
+       int i, j, min_ij;
+       float min, min2;
+       min = min2 = 1e30; min_ij = -1;
+       for (i = 0; i < 4; ++i) {
+               for (j = i; j < 4; ++j) {
+                       if (q[i<<2|j] < min) min_ij = i<<2|j, min2 = min, min = q[i<<2|j];
+                       else if (q[i<<2|j] < min2) min2 = q[i<<2|j];
+               }
+       }
+       return (min_ij>>2&3) == (min_ij&3)? 0 : 1<<18 | (min_ij>>2&3)<<16 | (min_ij&3) | (int)(min2 - min + .499) << 2;
+}
+
+int main_phase(int argc, char *argv[])
+{
+       extern void bam_init_header_hash(bam_header_t *header);
+       int c, tid, pos, vpos = 0, n, lasttid = -1, max_vpos = 0;
+       const bam_pileup1_t *plp;
+       bam_plp_t iter;
+       bam_header_t *h;
+       nseq_t *seqs;
+       uint64_t *cns = 0;
+       phaseg_t g;
+       char *fn_list = 0;
+       khash_t(set64) *set = 0;
+       errmod_t *em;
+       uint16_t *bases;
+
+       memset(&g, 0, sizeof(phaseg_t));
+       g.flag = FLAG_FIX_CHIMERA;
+       g.min_varLOD = 37; g.k = 13; g.min_baseQ = 13; g.max_depth = 256;
+       while ((c = getopt(argc, argv, "Q:eFq:k:b:l:D:A:")) >= 0) {
+               switch (c) {
+                       case 'D': g.max_depth = atoi(optarg); break;
+                       case 'q': g.min_varLOD = atoi(optarg); break;
+                       case 'Q': g.min_baseQ = atoi(optarg); break;
+                       case 'k': g.k = atoi(optarg); break;
+                       case 'F': g.flag &= ~FLAG_FIX_CHIMERA; break;
+                       case 'e': g.flag |= FLAG_LIST_EXCL; break;
+                       case 'A': g.flag |= FLAG_DROP_AMBI; break;
+                       case 'b': g.pre = strdup(optarg); break;
+                       case 'l': fn_list = strdup(optarg); break;
+               }
+       }
+       if (argc == optind) {
+               fprintf(stderr, "\n");
+               fprintf(stderr, "Usage:   samtools phase [options] <in.bam>\n\n");
+               fprintf(stderr, "Options: -k INT    block length [%d]\n", g.k);
+               fprintf(stderr, "         -b STR    prefix of BAMs to output [null]\n");
+               fprintf(stderr, "         -q INT    min het phred-LOD [%d]\n", g.min_varLOD);
+               fprintf(stderr, "         -Q INT    min base quality in het calling [%d]\n", g.min_baseQ);
+               fprintf(stderr, "         -D INT    max read depth [%d]\n", g.max_depth);
+//             fprintf(stderr, "         -l FILE   list of sites to phase [null]\n");
+               fprintf(stderr, "         -F        do not attempt to fix chimeras\n");
+               fprintf(stderr, "         -A        drop reads with ambiguous phase\n");
+//             fprintf(stderr, "         -e        do not discover SNPs (effective with -l)\n");
+               fprintf(stderr, "\n");
+               return 1;
+       }
+       g.fp = strcmp(argv[optind], "-")? bam_open(argv[optind], "r") : bam_dopen(fileno(stdin), "r");
+       h = bam_header_read(g.fp);
+       if (fn_list) { // read the list of sites to phase
+               bam_init_header_hash(h);
+               set = loadpos(fn_list, h);
+               free(fn_list);
+       } else g.flag &= ~FLAG_LIST_EXCL;
+       if (g.pre) { // open BAMs to write
+               char *s = malloc(strlen(g.pre) + 20);
+               strcpy(s, g.pre); strcat(s, ".0.bam"); g.out[0] = bam_open(s, "w");
+               strcpy(s, g.pre); strcat(s, ".1.bam"); g.out[1] = bam_open(s, "w");
+               strcpy(s, g.pre); strcat(s, ".chimera.bam"); g.out[2] = bam_open(s, "w");
+               for (c = 0; c <= 2; ++c) bam_header_write(g.out[c], h);
+               free(s);
+       }
+
+       iter = bam_plp_init(readaln, &g);
+       g.vpos_shift = 0;
+       seqs = kh_init(64);
+       em = errmod_init(1. - 0.83);
+       bases = calloc(g.max_depth, 2);
+       printf("CC\n");
+       printf("CC\tDescriptions:\nCC\n");
+       printf("CC\t  CC      comments\n");
+       printf("CC\t  PS      start of a phase set\n");
+       printf("CC\t  FL      filtered region\n");
+       printf("CC\t  M[012]  markers; 0 for singletons, 1 for phased and 2 for filtered\n");
+       printf("CC\t  EV      supporting reads; SAM format\n");
+       printf("CC\t  //      end of a phase set\nCC\n");
+       printf("CC\tFormats of PS, FL and M[012] lines (1-based coordinates):\nCC\n");
+       printf("CC\t  PS  chr  phaseSetStart  phaseSetEnd\n");
+       printf("CC\t  FL  chr  filterStart    filterEnd\n");
+       printf("CC\t  M?  chr  PS  pos  allele0  allele1  hetIndex  #supports0  #errors0  #supp1  #err1\n");
+       printf("CC\nCC\n");
+       fflush(stdout);
+       while ((plp = bam_plp_auto(iter, &tid, &pos, &n)) != 0) {
+               int i, k, c, tmp, dophase = 1, in_set = 0;
+               float q[16];
+               if (tid < 0) break;
+               if (tid != lasttid) { // change of chromosome
+                       g.vpos_shift = 0;
+                       if (lasttid >= 0) {
+                               seqs = shrink_hash(seqs);
+                               phase(&g, h->target_name[lasttid], vpos, cns, seqs);
+                               update_vpos(0x7fffffff, seqs);
+                       }
+                       lasttid = tid;
+                       vpos = 0;
+               }
+               if (set && kh_get(set64, set, (uint64_t)tid<<32 | pos) != kh_end(set)) in_set = 1;
+               if (n > g.max_depth) continue; // do not proceed if the depth is too high
+               // fill the bases array and check if there is a variant
+               for (i = k = 0; i < n; ++i) {
+                       const bam_pileup1_t *p = plp + i;
+                       uint8_t *seq;
+                       int q, baseQ, b;
+                       if (p->is_del || p->is_refskip) continue;
+                       baseQ = bam1_qual(p->b)[p->qpos];
+                       if (baseQ < g.min_baseQ) continue;
+                       seq = bam1_seq(p->b);
+                       b = bam_nt16_nt4_table[bam1_seqi(seq, p->qpos)];
+                       if (b > 3) continue;
+                       q = baseQ < p->b->core.qual? baseQ : p->b->core.qual;
+                       if (q < 4) q = 4;
+                       if (q > 63) q = 63;
+                       bases[k++] = q<<5 | (int)bam1_strand(p->b)<<4 | b;
+               }
+               if (k == 0) continue;
+               errmod_cal(em, k, 4, bases, q); // compute genotype likelihood
+               c = gl2cns(q); // get the consensus
+               // tell if to proceed
+               if (set && (g.flag&FLAG_LIST_EXCL) && !in_set) continue; // not in the list
+               if (!in_set && (c&0xffff)>>2 < g.min_varLOD) continue; // not a variant
+               // add the variant
+               if (vpos == max_vpos) {
+                       max_vpos = max_vpos? max_vpos<<1 : 128;
+                       cns = realloc(cns, max_vpos * 8);
+               }
+               cns[vpos] = (uint64_t)pos<<32 | c;
+               for (i = 0; i < n; ++i) {
+                       const bam_pileup1_t *p = plp + i;
+                       uint64_t key;
+                       khint_t k;
+                       uint8_t *seq = bam1_seq(p->b);
+                       frag_t *f;
+                       if (p->is_del || p->is_refskip) continue;
+                       if (p->b->core.qual == 0) continue;
+                       // get the base code
+                       c = nt16_nt4_table[(int)bam1_seqi(seq, p->qpos)];
+                       if (c == (cns[vpos]&3)) c = 1;
+                       else if (c == (cns[vpos]>>16&3)) c = 2;
+                       else c = 0;
+                       // write to seqs
+                       key = X31_hash_string(bam1_qname(p->b));
+                       k = kh_put(64, seqs, key, &tmp);
+                       f = &kh_val(seqs, k);
+                       if (tmp == 0) { // present in the hash table
+                               if (vpos - f->vpos + 1 < MAX_VARS) {
+                                       f->vlen = vpos - f->vpos + 1;
+                                       f->seq[f->vlen-1] = c;
+                                       f->end = bam_calend(&p->b->core, bam1_cigar(p->b));
+                               }
+                               dophase = 0;
+                       } else { // absent
+                               memset(f->seq, 0, MAX_VARS);
+                               f->beg = p->b->core.pos;
+                               f->end = bam_calend(&p->b->core, bam1_cigar(p->b));
+                               f->vpos = vpos, f->vlen = 1, f->seq[0] = c, f->single = f->phased = f->flip = f->ambig = 0;
+                       }
+               }
+               if (dophase) {
+                       seqs = shrink_hash(seqs);
+                       phase(&g, h->target_name[tid], vpos, cns, seqs);
+                       update_vpos(vpos, seqs);
+                       cns[0] = cns[vpos];
+                       vpos = 0;
+               }
+               ++vpos;
+       }
+       if (tid >= 0) phase(&g, h->target_name[tid], vpos, cns, seqs);
+       bam_header_destroy(h);
+       bam_plp_destroy(iter);
+       bam_close(g.fp);
+       kh_destroy(64, seqs);
+       kh_destroy(set64, set);
+       free(cns);
+       errmod_destroy(em);
+       free(bases);
+       if (g.pre) {
+               for (c = 0; c <= 2; ++c) bam_close(g.out[c]);
+               free(g.pre); free(g.b);
+       }
+       return 0;
+}