--- /dev/null
+#include <assert.h>
+#include "bam.h"
+#include "bam2bcf.h"
+#include "ksort.h"
+#include "kaln.h"
+
+#define INDEL_DEBUG
+
+#define MINUS_CONST 0x10000000
+#define INDEL_WINDOW_SIZE 50
+#define INDEL_BAD_SCORE 10000
+
+static int tpos2qpos(const bam1_core_t *c, const uint32_t *cigar, int32_t tpos, int is_left, int32_t *_tpos)
+{
+ int k, x = c->pos, y = 0, last_y = 0;
+ *_tpos = c->pos;
+ for (k = 0; k < c->n_cigar; ++k) {
+ int op = cigar[k] & BAM_CIGAR_MASK;
+ int l = cigar[k] >> BAM_CIGAR_SHIFT;
+ if (op == BAM_CMATCH) {
+ if (c->pos > tpos) return y;
+ if (x + l > tpos) {
+ *_tpos = tpos;
+ return y + (tpos - x);
+ }
+ x += l; y += l;
+ last_y = y;
+ } else if (op == BAM_CINS || op == BAM_CSOFT_CLIP) y += l;
+ else if (op == BAM_CDEL || op == BAM_CREF_SKIP) {
+ if (x + l > tpos) {
+ *_tpos = is_left? x : x + l;
+ return y;
+ }
+ x += l;
+ }
+ }
+ *_tpos = x;
+ return last_y;
+}
+// l is the relative gap length and l_run is the length of the homopolymer on the reference
+static inline int est_seqQ(const bcf_callaux_t *bca, int l, int l_run)
+{
+ int q, qh;
+ q = bca->openQ + bca->extQ * (abs(l) - 1);
+ qh = l_run >= 3? (int)(bca->tandemQ * (double)l / l_run + .499) : 1000;
+ return q < qh? q : qh;
+}
+
+int bcf_call_gap_prep(int n, int *n_plp, bam_pileup1_t **plp, int pos, bcf_callaux_t *bca, const char *ref)
+{
+ extern void ks_introsort_uint32_t(int, uint32_t*);
+ int i, s, j, k, t, n_types, *types, max_rd_len, left, right, max_ins, *score, N, K, l_run, ref_type;
+ char *inscns = 0, *ref2, *query;
+ if (ref == 0 || bca == 0) return -1;
+ // determine if there is a gap
+ for (s = 0; s < n; ++s) {
+ for (i = 0; i < n_plp[s]; ++i)
+ if (plp[s][i].indel != 0) break;
+ if (i < n_plp[s]) break;
+ }
+ if (s == n) return -1; // there is no indel at this position.
+ { // find out how many types of indels are present
+ int m;
+ uint32_t *aux;
+ aux = calloc(n + 1, 4);
+ m = max_rd_len = 0;
+ aux[m++] = MINUS_CONST; // zero indel is always a type
+ for (s = N = 0; s < n; ++s) {
+ N += n_plp[s]; // N is the total number of reads
+ for (i = 0; i < n_plp[s]; ++i) {
+ const bam_pileup1_t *p = plp[s] + i;
+ if (p->indel != 0)
+ aux[m++] = MINUS_CONST + p->indel;
+ j = bam_cigar2qlen(&p->b->core, bam1_cigar(p->b));
+ if (j > max_rd_len) max_rd_len = j;
+ }
+ }
+ ks_introsort(uint32_t, m, aux);
+ // squeeze out identical types
+ for (i = 1, n_types = 1; i < m; ++i)
+ if (aux[i] != aux[i-1]) ++n_types;
+ assert(n_types > 1); // there must at least one type of non-reference indel
+ types = (int*)calloc(n_types, sizeof(int));
+ t = 0;
+ types[t++] = aux[0] - MINUS_CONST;
+ for (i = 1; i < m; ++i)
+ if (aux[i] != aux[i-1])
+ types[t++] = aux[i] - MINUS_CONST;
+ free(aux);
+ for (t = 0; t < n_types; ++t)
+ if (types[t] == 0) break;
+ ref_type = t; // the index of the reference type (0)
+ assert(n_types < 64);
+ }
+ { // calculate left and right boundary
+ left = pos > INDEL_WINDOW_SIZE? pos - INDEL_WINDOW_SIZE : 0;
+ right = pos + INDEL_WINDOW_SIZE;
+ if (types[0] < 0) right -= types[0];
+ // in case the alignments stand out the reference
+ for (i = pos; i < right; ++i)
+ if (ref[i] == 0) break;
+ right = i;
+ }
+ { // the length of the homopolymer run around the current position
+ int c = bam_nt16_table[(int)ref[pos + 1]];
+ if (c == 15) l_run = 1;
+ else {
+ for (i = pos + 2; ref[i]; ++i)
+ if (bam_nt16_table[(int)ref[i]] != c) break;
+ l_run = i;
+ for (i = pos; i >= 0; --i)
+ if (bam_nt16_table[(int)ref[i]] != c) break;
+ l_run -= i + 1;
+ }
+ }
+ // construct the consensus sequence
+ max_ins = types[n_types - 1]; // max_ins is at least 0
+ if (max_ins > 0) {
+ int *inscns_aux = calloc(4 * n_types * max_ins, sizeof(int));
+ // count the number of occurrences of each base at each position for each type of insertion
+ for (t = 0; t < n_types; ++t) {
+ if (types[t] > 0) {
+ for (s = 0; s < n; ++s) {
+ for (i = 0; i < n_plp[s]; ++i) {
+ bam_pileup1_t *p = plp[s] + i;
+ if (p->indel == types[t]) {
+ uint8_t *seq = bam1_seq(p->b);
+ for (k = 1; k <= p->indel; ++k) {
+ int c = bam_nt16_nt4_table[bam1_seqi(seq, p->qpos + k)];
+ if (c < 4) ++inscns_aux[(t*max_ins+(k-1))*4 + c];
+ }
+ }
+ }
+ }
+ }
+ }
+ // use the majority rule to construct the consensus
+ inscns = calloc(n_types * max_ins, 1);
+ for (t = 0; t < n_types; ++t) {
+ for (j = 0; j < types[t]; ++j) {
+ int max = 0, max_k = -1, *ia = &inscns_aux[(t*max_ins+j)*4];
+ for (k = 0; k < 4; ++k)
+ if (ia[k] > max)
+ max = ia[k], max_k = k;
+ inscns[t*max_ins + j] = max? max_k : 4;
+ }
+ }
+ free(inscns_aux);
+ }
+ // compute the likelihood given each type of indel for each read
+ ref2 = calloc(right - left + max_ins + 2, 1);
+ query = calloc(right - left + max_rd_len + max_ins + 2, 1);
+ score = calloc(N * n_types, sizeof(int));
+ for (t = 0; t < n_types; ++t) {
+ int l;
+ ka_param2_t ap = ka_param2_qual;
+ ap.band_width = abs(types[t]) + 3;
+ // write ref2
+ for (k = 0, j = left; j <= pos; ++j)
+ ref2[k++] = bam_nt16_nt4_table[bam_nt16_table[(int)ref[j]]];
+ if (types[t] <= 0) j += -types[t];
+ else for (l = 0; l < types[t]; ++l)
+ ref2[k++] = inscns[t*max_ins + l];
+ if (types[0] < 0) { // mask deleted sequences to avoid a particular error in the model.
+ int jj, tmp = types[t] >= 0? -types[0] : -types[0] + types[t];
+ for (jj = 0; jj < tmp && j < right && ref[j]; ++jj, ++j)
+ ref2[k++] = 4;
+ }
+ for (; j < right && ref[j]; ++j)
+ ref2[k++] = bam_nt16_nt4_table[bam_nt16_table[(int)ref[j]]];
+ if (j < right) right = j;
+ // align each read to ref2
+ for (s = K = 0; s < n; ++s) {
+ for (i = 0; i < n_plp[s]; ++i, ++K) {
+ bam_pileup1_t *p = plp[s] + i;
+ int qbeg, qend, tbeg, tend, sc;
+ uint8_t *seq = bam1_seq(p->b);
+ // determine the start and end of sequences for alignment
+ qbeg = tpos2qpos(&p->b->core, bam1_cigar(p->b), left, 0, &tbeg);
+ qend = tpos2qpos(&p->b->core, bam1_cigar(p->b), right, 1, &tend);
+ assert(tbeg >= left);
+ // write the query sequence
+ for (l = qbeg; l < qend; ++l)
+ query[l - qbeg] = bam_nt16_nt4_table[bam1_seqi(seq, l)];
+ // do alignment; this takes most of computing time for indel calling
+#ifdef INDEL_DEBUG
+ for (sc = 0; sc < tend - tbeg + types[t]; ++sc)
+ fputc("ACGTN"[(int)ref2[tbeg-left+sc]], stderr);
+ fputc('\n', stderr);
+ for (sc = 0; sc < qend - qbeg; ++sc) fputc("ACGTN"[(int)query[qbeg + sc]], stderr);
+ fputc('\n', stderr);
+#endif
+ sc = ka_global_score((uint8_t*)ref2 + tbeg - left, tend - tbeg + abs(types[t]),
+ (uint8_t*)query + qbeg, qend - qbeg, &ap);
+#ifdef INDEL_DEBUG
+ fprintf(stderr, "pos=%d type=%d read=%d:%d name=%s score=%d\n", pos, types[t], s, i, bam1_qname(p->b), sc);
+#endif
+ score[K*n_types + t] = -sc;
+ }
+ }
+ }
+ free(ref2); free(query);
+ { // choose the top 4 indel types; reference must be included
+ }
+ { // compute indelQ
+ int *sc, tmp, *sumq;
+ sc = alloca(n_types * sizeof(int));
+ sumq = alloca(n_types * sizeof(int));
+ memset(sumq, 0, sizeof(int) * n_types);
+ for (s = K = 0; s < n; ++s) {
+ for (i = 0; i < n_plp[s]; ++i, ++K) {
+ bam_pileup1_t *p = plp[s] + i;
+ int *sct = &score[K*n_types], indelQ;
+ for (t = 0; t < n_types; ++t) sc[t] = sct[t]<<6 | t;
+ for (t = 1; t < n_types; ++t) // insertion sort
+ for (j = t; j > 0 && sc[j] < sc[j-1]; --j)
+ tmp = sc[j], sc[j] = sc[j-1], sc[j-1] = tmp;
+ /* errmod_cal() assumes that if the call is wrong, the
+ * likelihoods of other events are equal. This is about
+ * right for substitutions, but is not desired for
+ * indels. To reuse errmod_cal(), I have to make
+ * compromise for multi-allelic indels.
+ */
+ if ((sc[0]&0x3f) == ref_type) {
+ indelQ = (sc[1]>>6) - (sc[0]>>6);
+ tmp = est_seqQ(bca, types[sc[1]&0x3f], l_run);
+ } else {
+ for (t = 0; t < n_types; ++t) // look for the reference type
+ if ((sc[t]&0x3f) == ref_type) break;
+ indelQ = (sc[t]>>6) - (sc[0]>>6);
+ tmp = est_seqQ(bca, types[sc[0]&0x3f], l_run);
+ }
+ if (indelQ > tmp) indelQ = tmp;
+ if (indelQ > p->b->core.qual) indelQ = p->b->core.qual;
+ if (indelQ > bca->capQ) indelQ = bca->capQ;
+ p->aux = (sc[0]&0x3f)<<8 | indelQ;
+ sumq[sc[0]&0x3f] += indelQ;
+ }
+ }
+ // determine bca->indel_types[]
+ for (t = 0; t < n_types; ++t)
+ sumq[t] = sumq[t]<<6 | t;
+ for (t = 1; t < n_types; ++t) // insertion sort
+ for (j = t; j > 0 && sumq[j] < sumq[j-1]; --j)
+ tmp = sumq[j], sumq[j] = sumq[j-1], sumq[j-1] = tmp;
+ for (t = 0; t < n_types; ++t) // look for the reference type
+ if ((sumq[t]&0x3f) == ref_type) break;
+ if (t) { // then move the reference type to the first
+ tmp = sumq[t];
+ for (; t > 0; --t) sumq[t] = sumq[t-1];
+ sumq[0] = tmp;
+ }
+ for (t = 0; t < 4; ++t) bca->indel_types[t] = B2B_INDEL_NULL;
+ for (t = 0; t < 4 && t < n_types; ++t)
+ bca->indel_types[t] = types[sumq[t]&0x3f];
+ }
+ // FIXME: to set the inserted sequence
+ free(score);
+ // free
+ free(types); free(inscns);
+ return 0;
+}
-2, -2, -2, -2, -2
};
+int aln_sm_qual[] = {
+ 0, -23, -23, -23, 0,
+ -23, 0, -23, -23, 0,
+ -23, -23, 0, -23, 0,
+ -23, -23, -23, 0, 0,
+ 0, 0, 0, 0, 0
+};
+
ka_param_t ka_param_blast = { 5, 2, 5, 2, aln_sm_blast, 5, 50 };
ka_param_t ka_param_aa2aa = { 10, 2, 10, 2, aln_sm_blosum62, 22, 50 };
+ka_param2_t ka_param2_qual = { 35, 5, 35, 5, 35, 5, 0, 0, aln_sm_qual, 5, 50 };
+
static uint32_t *ka_path2cigar32(const path_t *path, int path_len, int *n_cigar)
{
int i, n;
}
typedef struct {
- uint8_t Mt:3, It:2, Dt:2;
+ uint8_t Mt:3, It:2, Dt:3;
} dpcell_t;
typedef struct {
score_matrix = ap->matrix;
N_MATRIX_ROW = ap->row;
- *n_cigar = 0;
+ if (n_cigar) *n_cigar = 0;
if (len1 == 0 || len2 == 0) return 0;
/* calculate b1 and b2 */
return cigar;
}
+
+typedef struct {
+ int M, I, D;
+} score_aux_t;
+
+#define MINUS_INF -0x40000000
+
+// matrix: len2 rows and len1 columns
+int ka_global_score(const uint8_t *_seq1, int len1, const uint8_t *_seq2, int len2, const ka_param2_t *ap)
+{
+
+#define __score_aux(_p, _q0, _sc, _io, _ie, _do, _de) { \
+ int t1, t2; \
+ score_aux_t *_q; \
+ _q = _q0; \
+ _p->M = _q->M >= _q->I? _q->M : _q->I; \
+ _p->M = _p->M >= _q->D? _p->M : _q->D; \
+ _p->M += (_sc); \
+ ++_q; t1 = _q->M - _io - _ie; t2 = _q->I - _ie; _p->I = t1 >= t2? t1 : t2; \
+ _q = _p-1; t1 = _q->M - _do - _de; t2 = _q->D - _de; _p->D = t1 >= t2? t1 : t2; \
+ }
+
+ int i, j, bw, scmat_size = ap->row, *scmat = ap->matrix, ret;
+ const uint8_t *seq1, *seq2;
+ score_aux_t *curr, *last, *swap;
+ bw = abs(len1 - len2) + ap->band_width;
+ i = len1 > len2? len1 : len2;
+ if (bw > i + 1) bw = i + 1;
+ seq1 = _seq1 - 1; seq2 = _seq2 - 1;
+ curr = calloc(len1 + 2, sizeof(score_aux_t));
+ last = calloc(len1 + 2, sizeof(score_aux_t));
+ { // the zero-th row
+ int x, end = len1;
+ score_aux_t *p;
+ j = 0;
+ x = j + bw; end = len1 < x? len1 : x; // band end
+ p = curr;
+ p->M = 0; p->I = p->D = MINUS_INF;
+ for (i = 1, p = &curr[1]; i <= end; ++i, ++p)
+ p->M = p->I = MINUS_INF, p->D = -(ap->edo + ap->ede * i);
+ p->M = p->I = p->D = MINUS_INF;
+ swap = curr; curr = last; last = swap;
+ }
+ for (j = 1; j < len2; ++j) {
+ int x, beg = 0, end = len1, *scrow, col_end;
+ score_aux_t *p;
+ x = j - bw; beg = 0 > x? 0 : x; // band start
+ x = j + bw; end = len1 < x? len1 : x; // band end
+ if (beg == 0) { // from zero-th column
+ p = curr;
+ p->M = p->D = MINUS_INF; p->I = -(ap->eio + ap->eie * j);
+ ++beg; // then beg = 1
+ }
+ scrow = scmat + seq2[j] * scmat_size;
+ if (end == len1) col_end = 1, --end;
+ else col_end = 0;
+ for (i = beg, p = &curr[beg]; i <= end; ++i, ++p)
+ __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->iio, ap->iie, ap->ido, ap->ide);
+ if (col_end) {
+ __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->eio, ap->eie, ap->ido, ap->ide);
+ ++p;
+ }
+ p->M = p->I = p->D = MINUS_INF;
+// for (i = 0; i <= len1; ++i) printf("(%d,%d,%d) ", curr[i].M, curr[i].I, curr[i].D); putchar('\n');
+ swap = curr; curr = last; last = swap;
+ }
+ { // the last row
+ int x, beg = 0, *scrow;
+ score_aux_t *p;
+ j = len2;
+ x = j - bw; beg = 0 > x? 0 : x; // band start
+ if (beg == 0) { // from zero-th column
+ p = curr;
+ p->M = p->D = MINUS_INF; p->I = -(ap->eio + ap->eie * j);
+ ++beg; // then beg = 1
+ }
+ scrow = scmat + seq2[j] * scmat_size;
+ for (i = beg, p = &curr[beg]; i < len1; ++i, ++p)
+ __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->iio, ap->iie, ap->edo, ap->ede);
+ __score_aux(p, &last[i-1], scrow[(int)seq1[i]], ap->eio, ap->eie, ap->edo, ap->ede);
+// for (i = 0; i <= len1; ++i) printf("(%d,%d,%d) ", curr[i].M, curr[i].I, curr[i].D); putchar('\n');
+ }
+ ret = curr[len1].M >= curr[len1].I? curr[len1].M : curr[len1].I;
+ ret = ret >= curr[len1].D? ret : curr[len1].D;
+ free(curr); free(last);
+ return ret;
+}
+
+#ifdef _MAIN
+int main(int argc, char *argv[])
+{
+// int len1 = 35, len2 = 35;
+// uint8_t *seq1 = (uint8_t*)"\0\0\3\3\2\0\0\0\1\0\2\1\2\1\3\2\3\3\3\0\2\3\2\1\1\3\3\3\2\3\3\1\0\0\1";
+// uint8_t *seq2 = (uint8_t*)"\0\0\3\3\2\0\0\0\1\0\2\1\2\1\3\2\3\3\3\0\2\3\2\1\1\3\3\3\2\3\3\1\0\1\0";
+ int len1 = 4, len2 = 4;
+ uint8_t *seq1 = (uint8_t*)"\1\0\0\1";
+ uint8_t *seq2 = (uint8_t*)"\1\0\1\0";
+ int sc;
+// ka_global_core(seq1, 2, seq2, 1, &ka_param_qual, &sc, 0);
+ sc = ka_global_score(seq1, len1, seq2, len2, &ka_param2_qual);
+ printf("%d\n", sc);
+ return 0;
+}
+#endif
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