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1 #include <stdio.h>
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2 #include <stdlib.h>
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3 #include <string.h>
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4 #include "bwtgap.h"
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5 #include "bwtaln.h"
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6
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7 #define STATE_M 0
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8 #define STATE_I 1
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9 #define STATE_D 2
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10
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11 #define aln_score(m,o,e,p) ((m)*(p)->s_mm + (o)*(p)->s_gapo + (e)*(p)->s_gape)
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12
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13 gap_stack_t *gap_init_stack(int max_mm, int max_gapo, int max_gape, const gap_opt_t *opt)
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14 {
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15 int i;
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16 gap_stack_t *stack;
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17 stack = (gap_stack_t*)calloc(1, sizeof(gap_stack_t));
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18 stack->n_stacks = aln_score(max_mm+1, max_gapo+1, max_gape+1, opt);
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19 stack->stacks = (gap_stack1_t*)calloc(stack->n_stacks, sizeof(gap_stack1_t));
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20 for (i = 0; i != stack->n_stacks; ++i) {
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21 gap_stack1_t *p = stack->stacks + i;
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22 p->m_entries = 4;
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23 p->stack = (gap_entry_t*)calloc(p->m_entries, sizeof(gap_entry_t));
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24 }
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25 return stack;
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26 }
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27
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28 void gap_destroy_stack(gap_stack_t *stack)
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29 {
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30 int i;
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31 for (i = 0; i != stack->n_stacks; ++i) free(stack->stacks[i].stack);
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32 free(stack->stacks);
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33 free(stack);
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34 }
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35
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36 static void gap_reset_stack(gap_stack_t *stack)
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37 {
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38 int i;
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39 for (i = 0; i != stack->n_stacks; ++i)
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40 stack->stacks[i].n_entries = 0;
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41 stack->best = stack->n_stacks;
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42 stack->n_entries = 0;
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43 }
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44
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45 static inline void gap_push(gap_stack_t *stack, int a, int i, bwtint_t k, bwtint_t l, int n_mm, int n_gapo, int n_gape,
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46 int state, int is_diff, const gap_opt_t *opt)
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47 {
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48 int score;
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49 gap_entry_t *p;
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50 gap_stack1_t *q;
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51 score = aln_score(n_mm, n_gapo, n_gape, opt);
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52 q = stack->stacks + score;
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53 if (q->n_entries == q->m_entries) {
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54 q->m_entries <<= 1;
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55 q->stack = (gap_entry_t*)realloc(q->stack, sizeof(gap_entry_t) * q->m_entries);
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56 }
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57 p = q->stack + q->n_entries;
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58 p->info = (u_int32_t)score<<21 | a<<20 | i; p->k = k; p->l = l;
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59 p->n_mm = n_mm; p->n_gapo = n_gapo; p->n_gape = n_gape; p->state = state;
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60 if (is_diff) p->last_diff_pos = i;
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61 ++(q->n_entries);
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62 ++(stack->n_entries);
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63 if (stack->best > score) stack->best = score;
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64 }
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65
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66 static inline void gap_pop(gap_stack_t *stack, gap_entry_t *e)
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67 {
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68 gap_stack1_t *q;
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69 q = stack->stacks + stack->best;
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70 *e = q->stack[q->n_entries - 1];
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71 --(q->n_entries);
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72 --(stack->n_entries);
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73 if (q->n_entries == 0 && stack->n_entries) { // reset best
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74 int i;
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75 for (i = stack->best + 1; i < stack->n_stacks; ++i)
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76 if (stack->stacks[i].n_entries != 0) break;
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77 stack->best = i;
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78 } else if (stack->n_entries == 0) stack->best = stack->n_stacks;
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79 }
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80
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81 static inline void gap_shadow(int x, int len, bwtint_t max, int last_diff_pos, bwt_width_t *w)
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82 {
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83 int i, j;
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84 for (i = j = 0; i < last_diff_pos; ++i) {
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85 if (w[i].w > x) w[i].w -= x;
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86 else if (w[i].w == x) {
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87 w[i].bid = 1;
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88 w[i].w = max - (++j);
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89 } // else should not happen
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90 }
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91 }
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92
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93 static inline int int_log2(uint32_t v)
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94 {
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95 int c = 0;
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96 if (v & 0xffff0000u) { v >>= 16; c |= 16; }
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97 if (v & 0xff00) { v >>= 8; c |= 8; }
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98 if (v & 0xf0) { v >>= 4; c |= 4; }
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99 if (v & 0xc) { v >>= 2; c |= 2; }
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100 if (v & 0x2) c |= 1;
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101 return c;
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102 }
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103
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104 bwt_aln1_t *bwt_match_gap(bwt_t *const bwts[2], int len, const ubyte_t *seq[2], bwt_width_t *w[2],
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105 bwt_width_t *seed_w[2], const gap_opt_t *opt, int *_n_aln, gap_stack_t *stack)
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106 {
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107 int best_score = aln_score(opt->max_diff+1, opt->max_gapo+1, opt->max_gape+1, opt);
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108 int best_diff = opt->max_diff + 1, max_diff = opt->max_diff;
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109 int best_cnt = 0;
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110 int max_entries = 0, j, _j, n_aln, m_aln;
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111 bwt_aln1_t *aln;
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112
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113 m_aln = 4; n_aln = 0;
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114 aln = (bwt_aln1_t*)calloc(m_aln, sizeof(bwt_aln1_t));
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115
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116 // check whether there are too many N
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117 for (j = _j = 0; j < len; ++j)
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118 if (seq[0][j] > 3) ++_j;
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119 if (_j > max_diff) {
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120 *_n_aln = n_aln;
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121 return aln;
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122 }
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123
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124 //for (j = 0; j != len; ++j) printf("#0 %d: [%d,%u]\t[%d,%u]\n", j, w[0][j].bid, w[0][j].w, w[1][j].bid, w[1][j].w);
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125 gap_reset_stack(stack); // reset stack
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126 gap_push(stack, 0, len, 0, bwts[0]->seq_len, 0, 0, 0, 0, 0, opt);
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127 gap_push(stack, 1, len, 0, bwts[0]->seq_len, 0, 0, 0, 0, 0, opt);
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128
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129 while (stack->n_entries) {
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130 gap_entry_t e;
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131 int a, i, m, m_seed = 0, hit_found, allow_diff, allow_M, tmp;
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132 bwtint_t k, l, cnt_k[4], cnt_l[4], occ;
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133 const bwt_t *bwt;
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134 const ubyte_t *str;
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135 const bwt_width_t *seed_width = 0;
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136 bwt_width_t *width;
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137
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138 if (max_entries < stack->n_entries) max_entries = stack->n_entries;
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139 if (stack->n_entries > opt->max_entries) break;
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140 gap_pop(stack, &e); // get the best entry
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141 k = e.k; l = e.l; // SA interval
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142 a = e.info>>20&1; i = e.info&0xffff; // strand, length
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143 if (!(opt->mode & BWA_MODE_NONSTOP) && e.info>>21 > best_score + opt->s_mm) break; // no need to proceed
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144
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145 m = max_diff - (e.n_mm + e.n_gapo);
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146 if (opt->mode & BWA_MODE_GAPE) m -= e.n_gape;
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147 if (m < 0) continue;
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148 bwt = bwts[1-a]; str = seq[a]; width = w[a];
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149 if (seed_w) { // apply seeding
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150 seed_width = seed_w[a];
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151 m_seed = opt->max_seed_diff - (e.n_mm + e.n_gapo);
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152 if (opt->mode & BWA_MODE_GAPE) m_seed -= e.n_gape;
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153 }
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154 //printf("#1\t[%d,%d,%d,%c]\t[%d,%d,%d]\t[%u,%u]\t[%u,%u]\t%d\n", stack->n_entries, a, i, "MID"[e.state], e.n_mm, e.n_gapo, e.n_gape, width[i-1].bid, width[i-1].w, k, l, e.last_diff_pos);
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155 if (i > 0 && m < width[i-1].bid) continue;
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156
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157 // check whether a hit is found
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158 hit_found = 0;
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159 if (i == 0) hit_found = 1;
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160 else if (m == 0 && (e.state == STATE_M || (opt->mode&BWA_MODE_GAPE) || e.n_gape == opt->max_gape)) { // no diff allowed
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161 if (bwt_match_exact_alt(bwt, i, str, &k, &l)) hit_found = 1;
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162 else continue; // no hit, skip
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163 }
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164
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165 if (hit_found) { // action for found hits
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166 int score = aln_score(e.n_mm, e.n_gapo, e.n_gape, opt);
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167 int do_add = 1;
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168 //printf("#2 hits found: %d:(%u,%u)\n", e.n_mm+e.n_gapo, k, l);
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169 if (n_aln == 0) {
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170 best_score = score;
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171 best_diff = e.n_mm + e.n_gapo;
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172 if (opt->mode & BWA_MODE_GAPE) best_diff += e.n_gape;
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173 if (!(opt->mode & BWA_MODE_NONSTOP))
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174 max_diff = (best_diff + 1 > opt->max_diff)? opt->max_diff : best_diff + 1; // top2 behaviour
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175 }
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176 if (score == best_score) best_cnt += l - k + 1;
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177 else if (best_cnt > opt->max_top2) break; // top2b behaviour
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178 if (e.n_gapo) { // check whether the hit has been found. this may happen when a gap occurs in a tandem repeat
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179 for (j = 0; j != n_aln; ++j)
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180 if (aln[j].k == k && aln[j].l == l) break;
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181 if (j < n_aln) do_add = 0;
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182 }
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183 if (do_add) { // append
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184 bwt_aln1_t *p;
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185 gap_shadow(l - k + 1, len, bwt->seq_len, e.last_diff_pos, width);
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186 if (n_aln == m_aln) {
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187 m_aln <<= 1;
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188 aln = (bwt_aln1_t*)realloc(aln, m_aln * sizeof(bwt_aln1_t));
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189 memset(aln + m_aln/2, 0, m_aln/2*sizeof(bwt_aln1_t));
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190 }
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191 p = aln + n_aln;
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192 p->n_mm = e.n_mm; p->n_gapo = e.n_gapo; p->n_gape = e.n_gape; p->a = a;
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193 p->k = k; p->l = l;
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194 p->score = score;
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195 ++n_aln;
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196 }
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197 continue;
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198 }
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199
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200 --i;
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201 bwt_2occ4(bwt, k - 1, l, cnt_k, cnt_l); // retrieve Occ values
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202 occ = l - k + 1;
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203 // test whether diff is allowed
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204 allow_diff = allow_M = 1;
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205 if (i > 0) {
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206 int ii = i - (len - opt->seed_len);
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207 if (width[i-1].bid > m-1) allow_diff = 0;
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208 else if (width[i-1].bid == m-1 && width[i].bid == m-1 && width[i-1].w == width[i].w) allow_M = 0;
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209 if (seed_w && ii > 0) {
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210 if (seed_width[ii-1].bid > m_seed-1) allow_diff = 0;
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211 else if (seed_width[ii-1].bid == m_seed-1 && seed_width[ii].bid == m_seed-1
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212 && seed_width[ii-1].w == seed_width[ii].w) allow_M = 0;
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213 }
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214 }
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215 // indels
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216 tmp = (opt->mode & BWA_MODE_LOGGAP)? int_log2(e.n_gape + e.n_gapo)/2+1 : e.n_gapo + e.n_gape;
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217 if (allow_diff && i >= opt->indel_end_skip + tmp && len - i >= opt->indel_end_skip + tmp) {
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218 if (e.state == STATE_M) { // gap open
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219 if (e.n_gapo < opt->max_gapo) { // gap open is allowed
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220 // insertion
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221 gap_push(stack, a, i, k, l, e.n_mm, e.n_gapo + 1, e.n_gape, STATE_I, 1, opt);
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222 // deletion
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223 for (j = 0; j != 4; ++j) {
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224 k = bwt->L2[j] + cnt_k[j] + 1;
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225 l = bwt->L2[j] + cnt_l[j];
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226 if (k <= l) gap_push(stack, a, i + 1, k, l, e.n_mm, e.n_gapo + 1, e.n_gape, STATE_D, 1, opt);
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227 }
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228 }
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229 } else if (e.state == STATE_I) { // extention of an insertion
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230 if (e.n_gape < opt->max_gape) // gap extention is allowed
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231 gap_push(stack, a, i, k, l, e.n_mm, e.n_gapo, e.n_gape + 1, STATE_I, 1, opt);
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232 } else if (e.state == STATE_D) { // extention of a deletion
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233 if (e.n_gape < opt->max_gape) { // gap extention is allowed
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234 if (e.n_gape + e.n_gapo < max_diff || occ < opt->max_del_occ) {
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235 for (j = 0; j != 4; ++j) {
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236 k = bwt->L2[j] + cnt_k[j] + 1;
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237 l = bwt->L2[j] + cnt_l[j];
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238 if (k <= l) gap_push(stack, a, i + 1, k, l, e.n_mm, e.n_gapo, e.n_gape + 1, STATE_D, 1, opt);
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239 }
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240 }
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241 }
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242 }
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243 }
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244 // mismatches
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245 if (allow_diff && allow_M) { // mismatch is allowed
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246 for (j = 1; j <= 4; ++j) {
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247 int c = (str[i] + j) & 3;
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248 int is_mm = (j != 4 || str[i] > 3);
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249 k = bwt->L2[c] + cnt_k[c] + 1;
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250 l = bwt->L2[c] + cnt_l[c];
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251 if (k <= l) gap_push(stack, a, i, k, l, e.n_mm + is_mm, e.n_gapo, e.n_gape, STATE_M, is_mm, opt);
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252 }
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253 } else if (str[i] < 4) { // try exact match only
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254 int c = str[i] & 3;
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255 k = bwt->L2[c] + cnt_k[c] + 1;
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256 l = bwt->L2[c] + cnt_l[c];
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257 if (k <= l) gap_push(stack, a, i, k, l, e.n_mm, e.n_gapo, e.n_gape, STATE_M, 0, opt);
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258 }
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259 }
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260
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261 *_n_aln = n_aln;
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262 //fprintf(stderr, "max_entries = %d\n", max_entries);
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263 return aln;
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264 }
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