| 1 | #include "AP_seq_protein.hxx" |
|---|
| 2 | #include <AP_pro_a_nucs.hxx> |
|---|
| 3 | |
|---|
| 4 | #include <AP_filter.hxx> |
|---|
| 5 | #include <ARB_Tree.hxx> |
|---|
| 6 | |
|---|
| 7 | #include <arb_str.h> |
|---|
| 8 | #include <climits> |
|---|
| 9 | |
|---|
| 10 | inline bool hasGap(AP_PROTEINS c) { return c & APP_GAP; } |
|---|
| 11 | inline bool isGap(AP_PROTEINS c) { return c == APP_GAP; } |
|---|
| 12 | |
|---|
| 13 | inline bool notHasGap(AP_PROTEINS c) { return !hasGap(c); } |
|---|
| 14 | inline bool notIsGap(AP_PROTEINS c) { return !isGap(c); } |
|---|
| 15 | |
|---|
| 16 | // #define ap_assert(bed) arb_assert(bed) |
|---|
| 17 | |
|---|
| 18 | AP_sequence_protein::AP_sequence_protein(const AliView *aliview) : |
|---|
| 19 | AP_combinableSeq(aliview), |
|---|
| 20 | seq_prot(NULp), |
|---|
| 21 | mut1(NULp), |
|---|
| 22 | mut2(NULp) |
|---|
| 23 | {} |
|---|
| 24 | |
|---|
| 25 | AP_sequence_protein::~AP_sequence_protein() { |
|---|
| 26 | delete [] mut2; |
|---|
| 27 | delete [] mut1; |
|---|
| 28 | delete [] seq_prot; |
|---|
| 29 | } |
|---|
| 30 | |
|---|
| 31 | AP_combinableSeq *AP_sequence_protein::dup() const { |
|---|
| 32 | return new AP_sequence_protein(get_aliview()); |
|---|
| 33 | } |
|---|
| 34 | |
|---|
| 35 | static AP_PROTEINS prot2AP_PROTEIN[26] = { |
|---|
| 36 | APP_A, |
|---|
| 37 | APP_B, |
|---|
| 38 | APP_C, |
|---|
| 39 | APP_D, |
|---|
| 40 | APP_E, |
|---|
| 41 | APP_F, |
|---|
| 42 | APP_G, |
|---|
| 43 | APP_H, |
|---|
| 44 | APP_I, |
|---|
| 45 | APP_ILLEGAL, // J |
|---|
| 46 | APP_K, |
|---|
| 47 | APP_L, |
|---|
| 48 | APP_M, |
|---|
| 49 | APP_N, |
|---|
| 50 | APP_ILLEGAL, // O |
|---|
| 51 | APP_P, |
|---|
| 52 | APP_Q, |
|---|
| 53 | APP_R, |
|---|
| 54 | APP_S, |
|---|
| 55 | APP_T, |
|---|
| 56 | APP_ILLEGAL, // U |
|---|
| 57 | APP_V, |
|---|
| 58 | APP_W, |
|---|
| 59 | APP_X, |
|---|
| 60 | APP_Y, |
|---|
| 61 | APP_Z |
|---|
| 62 | }; |
|---|
| 63 | |
|---|
| 64 | #define PROTEINS_TO_TEST 22 // 26 plus gap and star, minus 3 illegal, 'X', 'B' and 'Z' |
|---|
| 65 | |
|---|
| 66 | static AP_PROTEINS prot2test[PROTEINS_TO_TEST] = { // uses same indexing as prot_idx |
|---|
| 67 | APP_STAR, |
|---|
| 68 | APP_A, |
|---|
| 69 | APP_C, |
|---|
| 70 | APP_D, |
|---|
| 71 | APP_E, |
|---|
| 72 | APP_F, |
|---|
| 73 | APP_G, |
|---|
| 74 | APP_H, |
|---|
| 75 | APP_I, |
|---|
| 76 | APP_K, |
|---|
| 77 | APP_L, |
|---|
| 78 | APP_M, |
|---|
| 79 | APP_N, |
|---|
| 80 | APP_P, |
|---|
| 81 | APP_Q, |
|---|
| 82 | APP_R, |
|---|
| 83 | APP_S, |
|---|
| 84 | APP_T, |
|---|
| 85 | APP_V, |
|---|
| 86 | APP_W, |
|---|
| 87 | APP_Y, |
|---|
| 88 | APP_GAP |
|---|
| 89 | }; |
|---|
| 90 | |
|---|
| 91 | static int prot_idx[PROTEINS_TO_TEST] = { // uses same indexing as prot2test |
|---|
| 92 | // contains indexes for 'AWT_distance_meter->dist' |
|---|
| 93 | 0, // * |
|---|
| 94 | 1, // A |
|---|
| 95 | 3, // C |
|---|
| 96 | 4, // D |
|---|
| 97 | 5, // E |
|---|
| 98 | 6, // F |
|---|
| 99 | 7, // G |
|---|
| 100 | 8, // H |
|---|
| 101 | 9, // I |
|---|
| 102 | 10, // K |
|---|
| 103 | 11, // L |
|---|
| 104 | 12, // M |
|---|
| 105 | 13, // N |
|---|
| 106 | 14, // P |
|---|
| 107 | 15, // Q |
|---|
| 108 | 16, // R |
|---|
| 109 | 17, // S |
|---|
| 110 | 18, // T |
|---|
| 111 | 19, // V |
|---|
| 112 | 20, // W |
|---|
| 113 | 21, // Y |
|---|
| 114 | 23 // gap |
|---|
| 115 | }; |
|---|
| 116 | |
|---|
| 117 | inline const char *readable_combined_protein(AP_PROTEINS p) { |
|---|
| 118 | if (p == APP_X) { return "X"; } |
|---|
| 119 | if (p == APP_DOT) { return "."; } |
|---|
| 120 | |
|---|
| 121 | static char buffer[PROTEINS_TO_TEST+1]; |
|---|
| 122 | memset(buffer, 0, PROTEINS_TO_TEST+1); |
|---|
| 123 | char *bp = buffer; |
|---|
| 124 | const char *readable = "*ACDEFGHIKLMNPQRSTVWY-"; // same index as prot2test |
|---|
| 125 | |
|---|
| 126 | for (int b = 0; b<PROTEINS_TO_TEST; ++b) { |
|---|
| 127 | if (p&prot2test[b]) { |
|---|
| 128 | *bp++ = readable[b]; |
|---|
| 129 | } |
|---|
| 130 | } |
|---|
| 131 | return buffer; |
|---|
| 132 | } |
|---|
| 133 | |
|---|
| 134 | static char prot_mindist[PROTEINS_TO_TEST][PROTEINS_TO_TEST]; |
|---|
| 135 | static int min_mutations_initialized_for_codenr = -1; |
|---|
| 136 | |
|---|
| 137 | // OMA = one mutation away |
|---|
| 138 | // (speedup for huge table is approx. 4-7%) |
|---|
| 139 | #define OMA_SLOW_LOWMEM |
|---|
| 140 | |
|---|
| 141 | #if defined(ASSERTION_USED) && 0 |
|---|
| 142 | #define OMA_DOUBLE_CHECK |
|---|
| 143 | #endif |
|---|
| 144 | |
|---|
| 145 | #if defined(OMA_DOUBLE_CHECK) |
|---|
| 146 | # define IMPL_OMA_SLOW_LOWMEM |
|---|
| 147 | # define IMPL_OMA_FAST_BIGMEM |
|---|
| 148 | #else |
|---|
| 149 | # if defined(OMA_SLOW_LOWMEM) |
|---|
| 150 | # define IMPL_OMA_SLOW_LOWMEM |
|---|
| 151 | # else |
|---|
| 152 | # define IMPL_OMA_FAST_BIGMEM |
|---|
| 153 | # endif |
|---|
| 154 | #endif |
|---|
| 155 | |
|---|
| 156 | STATIC_ASSERT(APP_MAX == 4194303); |
|---|
| 157 | STATIC_ASSERT(sizeof(AP_PROTEINS) == 4); |
|---|
| 158 | |
|---|
| 159 | #if defined(IMPL_OMA_FAST_BIGMEM) |
|---|
| 160 | |
|---|
| 161 | static AP_PROTEINS one_mutation_away[APP_MAX+1]; // contains all proteins that are <= 1 nuc-mutations away from protein-combination used as index |
|---|
| 162 | STATIC_ASSERT(sizeof(one_mutation_away) == 16777216); // ~ 16Mb |
|---|
| 163 | |
|---|
| 164 | #endif |
|---|
| 165 | |
|---|
| 166 | #if defined(IMPL_OMA_SLOW_LOWMEM) |
|---|
| 167 | |
|---|
| 168 | static AP_PROTEINS one_mutation_away_0_7[256]; |
|---|
| 169 | static AP_PROTEINS one_mutation_away_8_15[256]; |
|---|
| 170 | static AP_PROTEINS one_mutation_away_16_23[256]; |
|---|
| 171 | |
|---|
| 172 | inline AP_PROTEINS calcOneMutationAway(AP_PROTEINS p) { |
|---|
| 173 | return AP_PROTEINS(one_mutation_away_0_7 [ p & 0xff] | |
|---|
| 174 | one_mutation_away_8_15 [(p>>8) & 0xff] | |
|---|
| 175 | one_mutation_away_16_23[(p>>16) & 0xff]); |
|---|
| 176 | } |
|---|
| 177 | |
|---|
| 178 | #endif |
|---|
| 179 | |
|---|
| 180 | |
|---|
| 181 | inline AP_PROTEINS oneMutationAway(AP_PROTEINS p) { |
|---|
| 182 | #if defined(OMA_SLOW_LOWMEM) |
|---|
| 183 | return calcOneMutationAway(p); |
|---|
| 184 | #else |
|---|
| 185 | return one_mutation_away[p]; |
|---|
| 186 | #endif |
|---|
| 187 | } |
|---|
| 188 | |
|---|
| 189 | static void update_min_mutations(int code_nr, const AWT_distance_meter *distance_meter) { |
|---|
| 190 | if (min_mutations_initialized_for_codenr != code_nr) { |
|---|
| 191 | for (int d = 0; d<PROTEINS_TO_TEST; ++d) { |
|---|
| 192 | int D = prot_idx[d]; |
|---|
| 193 | int D_bit = 1<<D; |
|---|
| 194 | |
|---|
| 195 | for (int s = 0; s<PROTEINS_TO_TEST; ++s) { |
|---|
| 196 | const AWT_PDP *dist = distance_meter->getDistance(prot_idx[s]); |
|---|
| 197 | |
|---|
| 198 | int i; |
|---|
| 199 | for (i = 0; i<3; ++i) { |
|---|
| 200 | if (dist->patd[i] & D_bit) break; |
|---|
| 201 | } |
|---|
| 202 | |
|---|
| 203 | prot_mindist[s][d] = char(i); |
|---|
| 204 | } |
|---|
| 205 | } |
|---|
| 206 | |
|---|
| 207 | |
|---|
| 208 | #if defined(IMPL_OMA_FAST_BIGMEM) |
|---|
| 209 | memset(one_mutation_away, 0, sizeof(one_mutation_away)); |
|---|
| 210 | #endif |
|---|
| 211 | #if defined(IMPL_OMA_SLOW_LOWMEM) |
|---|
| 212 | memset(one_mutation_away_0_7, 0, sizeof(one_mutation_away_0_7)); |
|---|
| 213 | memset(one_mutation_away_8_15, 0, sizeof(one_mutation_away_8_15)); |
|---|
| 214 | memset(one_mutation_away_16_23, 0, sizeof(one_mutation_away_16_23)); |
|---|
| 215 | #endif |
|---|
| 216 | |
|---|
| 217 | for (int s = 0; s<PROTEINS_TO_TEST; ++s) { |
|---|
| 218 | AP_PROTEINS oma = APP_ILLEGAL; |
|---|
| 219 | for (int d = 0; d<PROTEINS_TO_TEST; ++d) { |
|---|
| 220 | if (prot_mindist[s][d] == 1) { |
|---|
| 221 | oma = AP_PROTEINS(oma|prot2test[d]); |
|---|
| 222 | } |
|---|
| 223 | } |
|---|
| 224 | |
|---|
| 225 | AP_PROTEINS source = prot2test[s]; |
|---|
| 226 | oma = AP_PROTEINS(oma|source); |
|---|
| 227 | |
|---|
| 228 | #if defined(IMPL_OMA_FAST_BIGMEM) |
|---|
| 229 | one_mutation_away[source] = oma; |
|---|
| 230 | #endif |
|---|
| 231 | #if defined(IMPL_OMA_SLOW_LOWMEM) |
|---|
| 232 | uint32_t idx = source & 0xff; if (idx) one_mutation_away_0_7 [idx] = oma; |
|---|
| 233 | idx = (source>>8) & 0xff; if (idx) one_mutation_away_8_15 [idx] = oma; |
|---|
| 234 | idx = (source>>16) & 0xff; if (idx) one_mutation_away_16_23[idx] = oma; |
|---|
| 235 | #endif |
|---|
| 236 | } |
|---|
| 237 | |
|---|
| 238 | #if defined(IMPL_OMA_FAST_BIGMEM) |
|---|
| 239 | for (size_t i = 0; i<=APP_MAX; ++i) { |
|---|
| 240 | if (one_mutation_away[i] == APP_ILLEGAL) { |
|---|
| 241 | size_t j = i; |
|---|
| 242 | size_t b = 1; |
|---|
| 243 | AP_PROTEINS oma = APP_ILLEGAL; |
|---|
| 244 | |
|---|
| 245 | while (j) { |
|---|
| 246 | if (j&1) oma = AP_PROTEINS(oma|one_mutation_away[b]); |
|---|
| 247 | j >>= 1; |
|---|
| 248 | b <<= 1; |
|---|
| 249 | } |
|---|
| 250 | |
|---|
| 251 | one_mutation_away[i] = oma; |
|---|
| 252 | } |
|---|
| 253 | } |
|---|
| 254 | #endif |
|---|
| 255 | #if defined(IMPL_OMA_SLOW_LOWMEM) |
|---|
| 256 | for (int s = 0; s<8; s++) { |
|---|
| 257 | int b = 1<<s; |
|---|
| 258 | for (int i=b+1; i<256; i++) { |
|---|
| 259 | if (i & b) { |
|---|
| 260 | one_mutation_away_0_7[i] = AP_PROTEINS(one_mutation_away_0_7[i] | one_mutation_away_0_7[b]); |
|---|
| 261 | one_mutation_away_8_15[i] = AP_PROTEINS(one_mutation_away_8_15[i] | one_mutation_away_8_15[b]); |
|---|
| 262 | one_mutation_away_16_23[i] = AP_PROTEINS(one_mutation_away_16_23[i] | one_mutation_away_16_23[b]); |
|---|
| 263 | } |
|---|
| 264 | } |
|---|
| 265 | } |
|---|
| 266 | #endif |
|---|
| 267 | |
|---|
| 268 | #if defined(IMPL_OMA_FAST_BIGMEM) && defined(DEBUG) |
|---|
| 269 | for (size_t i = 0; i<=APP_MAX; ++i) { |
|---|
| 270 | if (one_mutation_away[i] == 0) { |
|---|
| 271 | fprintf(stderr, "oma[%s] is zero\n", readable_combined_protein(AP_PROTEINS(i))); |
|---|
| 272 | } |
|---|
| 273 | } |
|---|
| 274 | for (size_t i = 0; i<=APP_MAX; ++i) { |
|---|
| 275 | AP_PROTEINS two_mutations_away = one_mutation_away[one_mutation_away[i]]; |
|---|
| 276 | bool gap = hasGap(AP_PROTEINS(i)); |
|---|
| 277 | if ((!gap && two_mutations_away != APP_X) || (gap && two_mutations_away != APP_DOT)) { |
|---|
| 278 | // reached for a few amino-acid-combinations: C, F, C|F, K, M, K|M |
|---|
| 279 | // and for APP_ILLEGAL and APP_GAP as below for 3 mutations |
|---|
| 280 | fprintf(stderr, "tma[%s]", readable_combined_protein(AP_PROTEINS(i))); |
|---|
| 281 | fprintf(stderr, "=%s\n", readable_combined_protein(two_mutations_away)); |
|---|
| 282 | } |
|---|
| 283 | } |
|---|
| 284 | for (size_t i = 0; i<=APP_MAX; ++i) { |
|---|
| 285 | AP_PROTEINS three_mutations_away = one_mutation_away[one_mutation_away[one_mutation_away[i]]]; |
|---|
| 286 | bool gap = hasGap(AP_PROTEINS(i)); |
|---|
| 287 | if ((!gap && three_mutations_away != APP_X) || (gap && three_mutations_away != APP_DOT)) { |
|---|
| 288 | // only reached for i==APP_ILLEGAL and i==APP_GAP (result is wrong for latter) |
|---|
| 289 | fprintf(stderr, "3ma[%s]", readable_combined_protein(AP_PROTEINS(i))); |
|---|
| 290 | fprintf(stderr, "=%s\n", readable_combined_protein(three_mutations_away)); |
|---|
| 291 | } |
|---|
| 292 | } |
|---|
| 293 | #endif |
|---|
| 294 | |
|---|
| 295 | #if defined(OMA_DOUBLE_CHECK) |
|---|
| 296 | for (size_t i = 0; i<=APP_MAX; ++i) { |
|---|
| 297 | AP_PROTEINS p = AP_PROTEINS(i); |
|---|
| 298 | ap_assert(calcOneMutationAway(p) == one_mutation_away[p]); |
|---|
| 299 | } |
|---|
| 300 | #endif |
|---|
| 301 | |
|---|
| 302 | min_mutations_initialized_for_codenr = code_nr; |
|---|
| 303 | } |
|---|
| 304 | } |
|---|
| 305 | |
|---|
| 306 | |
|---|
| 307 | #if defined(DEBUG) |
|---|
| 308 | // #define SHOW_SEQ |
|---|
| 309 | #endif // DEBUG |
|---|
| 310 | |
|---|
| 311 | void AP_sequence_protein::set(const char *isequence) { |
|---|
| 312 | AWT_translator *translator = AWT_get_user_translator(get_aliview()->get_gb_main()); |
|---|
| 313 | update_min_mutations(translator->CodeNr(), translator->getDistanceMeter()); |
|---|
| 314 | |
|---|
| 315 | size_t sequence_len = get_sequence_length(); |
|---|
| 316 | |
|---|
| 317 | seq_prot = new AP_PROTEINS[sequence_len+1]; |
|---|
| 318 | mut1 = new AP_PROTEINS[sequence_len+1]; |
|---|
| 319 | mut2 = new AP_PROTEINS[sequence_len+1]; |
|---|
| 320 | |
|---|
| 321 | ap_assert(!get_filter()->does_bootstrap()); // bootstrapping not implemented for protein parsimony |
|---|
| 322 | |
|---|
| 323 | const AP_filter *filt = get_filter(); |
|---|
| 324 | const uchar *simplify = filt->get_simplify_table(); |
|---|
| 325 | int left_bases = sequence_len; |
|---|
| 326 | long filter_len = filt->get_length(); |
|---|
| 327 | |
|---|
| 328 | ap_assert(filt); |
|---|
| 329 | |
|---|
| 330 | size_t oidx = 0; // index for output sequence |
|---|
| 331 | |
|---|
| 332 | // check if initialized for correct instance of translator: |
|---|
| 333 | ap_assert(min_mutations_initialized_for_codenr == AWT_get_user_translator()->CodeNr()); |
|---|
| 334 | |
|---|
| 335 | for (int idx = 0; idx<filter_len && left_bases; ++idx) { |
|---|
| 336 | if (filt->use_position(idx)) { |
|---|
| 337 | char c = toupper(simplify[safeCharIndex(isequence[idx])]); |
|---|
| 338 | AP_PROTEINS p = APP_ILLEGAL; |
|---|
| 339 | |
|---|
| 340 | #if defined(SHOW_SEQ) |
|---|
| 341 | fputc(c, stdout); |
|---|
| 342 | #endif // SHOW_SEQ |
|---|
| 343 | |
|---|
| 344 | if (c >= 'A' && c <= 'Z') p = prot2AP_PROTEIN[c-'A']; |
|---|
| 345 | else if (c == '-') p = APP_GAP; |
|---|
| 346 | else if (c == '.') p = APP_DOT; |
|---|
| 347 | else if (c == '*') p = APP_STAR; |
|---|
| 348 | |
|---|
| 349 | if (p == APP_ILLEGAL) { |
|---|
| 350 | GB_warning(GBS_global_string("Invalid sequence character '%c' replaced by dot", c)); |
|---|
| 351 | p = APP_DOT; |
|---|
| 352 | } |
|---|
| 353 | |
|---|
| 354 | seq_prot[oidx] = p; |
|---|
| 355 | mut1[oidx] = oneMutationAway(p); |
|---|
| 356 | mut2[oidx] = oneMutationAway(mut1[oidx]); |
|---|
| 357 | |
|---|
| 358 | ++oidx; |
|---|
| 359 | --left_bases; |
|---|
| 360 | } |
|---|
| 361 | } |
|---|
| 362 | |
|---|
| 363 | ap_assert(oidx == sequence_len); |
|---|
| 364 | seq_prot[sequence_len] = APP_ILLEGAL; |
|---|
| 365 | |
|---|
| 366 | #if defined(SHOW_SEQ) |
|---|
| 367 | fputc('\n', stdout); |
|---|
| 368 | #endif // SHOW_SEQ |
|---|
| 369 | |
|---|
| 370 | mark_sequence_set(true); |
|---|
| 371 | } |
|---|
| 372 | |
|---|
| 373 | void AP_sequence_protein::unset() { |
|---|
| 374 | delete [] mut2; mut2 = NULp; |
|---|
| 375 | delete [] mut1; mut1 = NULp; |
|---|
| 376 | delete [] seq_prot; seq_prot = NULp; |
|---|
| 377 | mark_sequence_set(false); |
|---|
| 378 | } |
|---|
| 379 | |
|---|
| 380 | Mutations AP_sequence_protein::combine_seq(const AP_combinableSeq *lefts, const AP_combinableSeq *rights, char *mutation_per_site) { |
|---|
| 381 | // Note: changes done here should also be be applied to AP_seq_dna.cxx@combine_impl |
|---|
| 382 | |
|---|
| 383 | // now uses same algorithm as done till [877] |
|---|
| 384 | |
|---|
| 385 | const AP_sequence_protein *left = DOWNCAST(const AP_sequence_protein*, lefts); |
|---|
| 386 | const AP_sequence_protein *right = DOWNCAST(const AP_sequence_protein*, rights); |
|---|
| 387 | |
|---|
| 388 | size_t sequence_len = get_sequence_length(); |
|---|
| 389 | if (!seq_prot) { |
|---|
| 390 | seq_prot = new AP_PROTEINS[sequence_len + 1]; |
|---|
| 391 | mut1 = new AP_PROTEINS[sequence_len + 1]; |
|---|
| 392 | mut2 = new AP_PROTEINS[sequence_len + 1]; |
|---|
| 393 | } |
|---|
| 394 | |
|---|
| 395 | const AP_PROTEINS *p1 = left->get_sequence(); |
|---|
| 396 | const AP_PROTEINS *p2 = right->get_sequence(); |
|---|
| 397 | |
|---|
| 398 | const AP_PROTEINS *mut11 = left->get_mut1(); |
|---|
| 399 | const AP_PROTEINS *mut21 = left->get_mut2(); |
|---|
| 400 | const AP_PROTEINS *mut12 = right->get_mut1(); |
|---|
| 401 | const AP_PROTEINS *mut22 = right->get_mut2(); |
|---|
| 402 | |
|---|
| 403 | AP_PROTEINS *p = seq_prot; |
|---|
| 404 | const AP_weights *weights = get_weights(); |
|---|
| 405 | char *mutpsite = mutation_per_site; |
|---|
| 406 | |
|---|
| 407 | long result = 0; |
|---|
| 408 | // check if initialized for correct instance of translator: |
|---|
| 409 | ap_assert(min_mutations_initialized_for_codenr == AWT_get_user_translator()->CodeNr()); |
|---|
| 410 | |
|---|
| 411 | for (size_t idx = 0; idx<sequence_len; ++idx) { |
|---|
| 412 | AP_PROTEINS c1 = p1[idx]; |
|---|
| 413 | AP_PROTEINS c2 = p2[idx]; |
|---|
| 414 | |
|---|
| 415 | AP_PROTEINS onemut1 = mut11[idx]; |
|---|
| 416 | AP_PROTEINS onemut2 = mut12[idx]; |
|---|
| 417 | AP_PROTEINS twomut1 = mut21[idx]; |
|---|
| 418 | AP_PROTEINS twomut2 = mut22[idx]; |
|---|
| 419 | |
|---|
| 420 | ap_assert(c1 != APP_ILLEGAL); |
|---|
| 421 | ap_assert(c2 != APP_ILLEGAL); |
|---|
| 422 | |
|---|
| 423 | AP_PROTEINS contained_in_both = AP_PROTEINS(c1 & c2); |
|---|
| 424 | AP_PROTEINS contained_in_any = AP_PROTEINS(c1 | c2); |
|---|
| 425 | |
|---|
| 426 | AP_PROTEINS reachable_from_both_with_1_mut = AP_PROTEINS(onemut1 & onemut2); |
|---|
| 427 | AP_PROTEINS reachable_from_both_with_2_mut = AP_PROTEINS(twomut1 & twomut2); |
|---|
| 428 | |
|---|
| 429 | AP_PROTEINS max_cost_1 = AP_PROTEINS(contained_in_any & reachable_from_both_with_1_mut); |
|---|
| 430 | AP_PROTEINS max_cost_2 = AP_PROTEINS((contained_in_any & reachable_from_both_with_2_mut) | reachable_from_both_with_1_mut); |
|---|
| 431 | |
|---|
| 432 | if (contained_in_both) { // there are common proteins |
|---|
| 433 | p[idx] = contained_in_both; // store common proteins for both subtrees |
|---|
| 434 | mut1[idx] = max_cost_1; |
|---|
| 435 | mut2[idx] = max_cost_2; |
|---|
| 436 | } |
|---|
| 437 | else { // proteins are distinct |
|---|
| 438 | int mutations = INT_MAX; |
|---|
| 439 | |
|---|
| 440 | AP_PROTEINS reachable_from_both_with_3_mut = AP_PROTEINS((onemut1 & twomut2) | (onemut2 & twomut1)); // one with 1 mutation, other with 2 mutations |
|---|
| 441 | |
|---|
| 442 | AP_PROTEINS max_cost_3 = AP_PROTEINS(contained_in_any // = one w/o mutations, other with 3 mutations (=anything, i.e. & APP_DOT, skipped) |
|---|
| 443 | | reachable_from_both_with_3_mut); |
|---|
| 444 | |
|---|
| 445 | if (max_cost_1) { |
|---|
| 446 | // some proteins can be reached from both subtrees with 1 mutation |
|---|
| 447 | mutations = 1; |
|---|
| 448 | p[idx] = max_cost_1; |
|---|
| 449 | mut1[idx] = max_cost_2; |
|---|
| 450 | mut2[idx] = max_cost_3; |
|---|
| 451 | } |
|---|
| 452 | else { |
|---|
| 453 | AP_PROTEINS reachable_from_any_with_1_mut = AP_PROTEINS(onemut1 | onemut2); |
|---|
| 454 | |
|---|
| 455 | AP_PROTEINS max_cost_4 = AP_PROTEINS(reachable_from_any_with_1_mut // one with 1 mutation, other with 3 mutations (=anything, i.e. & APP_DOT, skipped) |
|---|
| 456 | | reachable_from_both_with_2_mut); |
|---|
| 457 | if (max_cost_2) { |
|---|
| 458 | // some proteins can be reached from both subtrees with 2 mutations |
|---|
| 459 | mutations = 2; |
|---|
| 460 | p[idx] = max_cost_2; |
|---|
| 461 | mut1[idx] = max_cost_3; |
|---|
| 462 | mut2[idx] = max_cost_4; |
|---|
| 463 | } |
|---|
| 464 | else { |
|---|
| 465 | ap_assert(max_cost_3); |
|---|
| 466 | AP_PROTEINS reachable_from_any_with_2_mut = AP_PROTEINS(twomut1 | twomut2); |
|---|
| 467 | |
|---|
| 468 | mutations = 3; |
|---|
| 469 | p[idx] = max_cost_3; |
|---|
| 470 | mut1[idx] = max_cost_4; |
|---|
| 471 | mut2[idx] = reachable_from_any_with_2_mut; // one with 2 mutations, other with 3 mutations |
|---|
| 472 | } |
|---|
| 473 | } |
|---|
| 474 | ap_assert(mutations >= 1 && mutations <= 3); |
|---|
| 475 | |
|---|
| 476 | if (mutpsite) mutpsite[idx] += mutations; // count mutations per site (unweighted) |
|---|
| 477 | result += mutations * weights->weight(idx); // count weighted or simple |
|---|
| 478 | |
|---|
| 479 | } |
|---|
| 480 | |
|---|
| 481 | AP_PROTEINS calc_mut1 = oneMutationAway(p[idx]); |
|---|
| 482 | mut1[idx] = AP_PROTEINS(mut1[idx] | calc_mut1); |
|---|
| 483 | AP_PROTEINS calc_mut2 = oneMutationAway(mut1[idx]); |
|---|
| 484 | mut2[idx] = AP_PROTEINS(mut2[idx] | calc_mut2); |
|---|
| 485 | } |
|---|
| 486 | |
|---|
| 487 | #if defined(DEBUG) && 0 |
|---|
| 488 | #define P1 75 |
|---|
| 489 | #define P2 90 |
|---|
| 490 | printf("Seq1: "); |
|---|
| 491 | for (long idx = P1; idx <= P2; ++idx) printf("%3i ", p1[idx]); |
|---|
| 492 | printf("\nSeq2: "); |
|---|
| 493 | for (long idx = P1; idx <= P2; ++idx) printf("%3i ", p2[idx]); |
|---|
| 494 | printf("\nCombine value: %f\n", float(result)); |
|---|
| 495 | #undef P1 |
|---|
| 496 | #undef P2 |
|---|
| 497 | #endif // DEBUG |
|---|
| 498 | |
|---|
| 499 | #if defined(DEBUG) && 0 |
|---|
| 500 | printf("\nCombine value: %f\n", float(result)); |
|---|
| 501 | #endif // DEBUG |
|---|
| 502 | |
|---|
| 503 | inc_combine_count(); |
|---|
| 504 | mark_sequence_set(true); |
|---|
| 505 | |
|---|
| 506 | ap_assert(result >= 0); |
|---|
| 507 | return result; |
|---|
| 508 | } |
|---|
| 509 | |
|---|
| 510 | Mutations AP_sequence_protein::mutations_if_combined_with(const AP_combinableSeq *other) { |
|---|
| 511 | // Note: uses stupid brute-force implementation |
|---|
| 512 | |
|---|
| 513 | AP_combinableSeq *tmp = dup(); |
|---|
| 514 | Mutations mut = tmp->combine_seq(this, other); // Note: calls inc_combine_count() |
|---|
| 515 | |
|---|
| 516 | delete tmp; |
|---|
| 517 | return mut; |
|---|
| 518 | } |
|---|
| 519 | |
|---|
| 520 | void AP_sequence_protein::partial_match(const AP_combinableSeq *part_, long *overlapPtr, long *penaltyPtr) const { |
|---|
| 521 | // matches the partial sequences 'part_' against 'this' |
|---|
| 522 | // '*penaltyPtr' is set to the number of mismatches (possibly weighted) |
|---|
| 523 | // '*overlapPtr' is set to the number of base positions both sequences overlap |
|---|
| 524 | // example: |
|---|
| 525 | // fullseq 'XXX---XXX' 'XXX---XXX' |
|---|
| 526 | // partialseq '-XX---XX-' '---XXX---' |
|---|
| 527 | // overlap 7 3 |
|---|
| 528 | // |
|---|
| 529 | // algorithm is similar to AP_sequence_protein::combine() |
|---|
| 530 | // Note: changes done here should also be be applied to AP_seq_dna.cxx@partial_match_impl |
|---|
| 531 | |
|---|
| 532 | const AP_sequence_protein *part = (const AP_sequence_protein *)part_; |
|---|
| 533 | |
|---|
| 534 | const AP_PROTEINS *pf = get_sequence(); |
|---|
| 535 | const AP_PROTEINS *pp = part->get_sequence(); |
|---|
| 536 | |
|---|
| 537 | const AP_weights *weights = get_weights(); |
|---|
| 538 | |
|---|
| 539 | long min_end; // minimum of both last non-gap positions |
|---|
| 540 | for (min_end = get_sequence_length()-1; min_end >= 0; --min_end) { |
|---|
| 541 | AP_PROTEINS both = AP_PROTEINS(pf[min_end]|pp[min_end]); |
|---|
| 542 | if (notHasGap(both)) { // last non-gap found |
|---|
| 543 | if (notHasGap(pf[min_end])) { // occurred in full sequence |
|---|
| 544 | for (; min_end >= 0; --min_end) { // search same in partial sequence |
|---|
| 545 | if (notHasGap(pp[min_end])) break; |
|---|
| 546 | } |
|---|
| 547 | } |
|---|
| 548 | else { |
|---|
| 549 | ap_assert(notHasGap(pp[min_end])); // occurred in partial sequence |
|---|
| 550 | for (; min_end >= 0; --min_end) { // search same in full sequence |
|---|
| 551 | if (notHasGap(pf[min_end])) break; |
|---|
| 552 | } |
|---|
| 553 | } |
|---|
| 554 | break; |
|---|
| 555 | } |
|---|
| 556 | } |
|---|
| 557 | |
|---|
| 558 | long penalty = 0; |
|---|
| 559 | long overlap = 0; |
|---|
| 560 | |
|---|
| 561 | if (min_end >= 0) { |
|---|
| 562 | long max_start; // maximum of both first non-gap positions |
|---|
| 563 | for (max_start = 0; max_start <= min_end; ++max_start) { |
|---|
| 564 | AP_PROTEINS both = AP_PROTEINS(pf[max_start]|pp[max_start]); |
|---|
| 565 | if (notHasGap(both)) { // first non-gap found |
|---|
| 566 | if (notHasGap(pf[max_start])) { // occurred in full sequence |
|---|
| 567 | for (; max_start <= min_end; ++max_start) { // search same in partial |
|---|
| 568 | if (notHasGap(pp[max_start])) break; |
|---|
| 569 | } |
|---|
| 570 | } |
|---|
| 571 | else { |
|---|
| 572 | ap_assert(notHasGap(pp[max_start])); // occurred in partial sequence |
|---|
| 573 | for (; max_start <= min_end; ++max_start) { // search same in full |
|---|
| 574 | if (notHasGap(pf[max_start])) break; |
|---|
| 575 | } |
|---|
| 576 | } |
|---|
| 577 | break; |
|---|
| 578 | } |
|---|
| 579 | } |
|---|
| 580 | |
|---|
| 581 | if (max_start <= min_end) { // if sequences overlap |
|---|
| 582 | for (long idx = max_start; idx <= min_end; ++idx) { |
|---|
| 583 | if ((pf[idx]&pp[idx]) == 0) { // bases are distinct (aka mismatch) |
|---|
| 584 | int mutations; |
|---|
| 585 | if (hasGap(AP_PROTEINS(pf[idx]|pp[idx]))) { // one is a gap |
|---|
| 586 | mutations = 3; |
|---|
| 587 | } |
|---|
| 588 | else { |
|---|
| 589 | mutations = INT_MAX; |
|---|
| 590 | for (int t1 = 0; t1<PROTEINS_TO_TEST && mutations>1; ++t1) { // with all proteins to test |
|---|
| 591 | if (pf[idx] & prot2test[t1]) { // if protein is contained in subtree |
|---|
| 592 | for (int t2 = 0; t2<PROTEINS_TO_TEST; ++t2) { |
|---|
| 593 | if (pp[idx] & prot2test[t2]) { |
|---|
| 594 | int mut = prot_mindist[t1][t2]; |
|---|
| 595 | if (mut<mutations) { |
|---|
| 596 | mutations = mut; |
|---|
| 597 | if (mutations < 2) break; // minimum reached -- abort |
|---|
| 598 | } |
|---|
| 599 | } |
|---|
| 600 | } |
|---|
| 601 | } |
|---|
| 602 | } |
|---|
| 603 | } |
|---|
| 604 | penalty += weights->weight(idx)*mutations; |
|---|
| 605 | } |
|---|
| 606 | } |
|---|
| 607 | overlap = (min_end-max_start+1)*3; |
|---|
| 608 | } |
|---|
| 609 | } |
|---|
| 610 | |
|---|
| 611 | *overlapPtr = overlap; |
|---|
| 612 | *penaltyPtr = penalty; |
|---|
| 613 | } |
|---|
| 614 | |
|---|
| 615 | AP_FLOAT AP_sequence_protein::count_weighted_bases() const { |
|---|
| 616 | AP_FLOAT wcount; |
|---|
| 617 | const AP_PROTEINS *sequence = get_sequence(); |
|---|
| 618 | |
|---|
| 619 | if (!sequence) wcount = -1.0; |
|---|
| 620 | else { |
|---|
| 621 | long sum = 0; |
|---|
| 622 | size_t sequence_len = get_sequence_length(); |
|---|
| 623 | |
|---|
| 624 | const AP_weights *weights = get_weights(); |
|---|
| 625 | |
|---|
| 626 | for (size_t idx = 0; idx<sequence_len; ++idx) { |
|---|
| 627 | if (notHasGap(sequence[idx])) { |
|---|
| 628 | sum += weights->weight(idx) * 2.0; |
|---|
| 629 | } |
|---|
| 630 | else if /*has gap but */ (notIsGap(sequence[idx])) { |
|---|
| 631 | sum += weights->weight(idx); |
|---|
| 632 | } |
|---|
| 633 | } |
|---|
| 634 | wcount = sum * 0.5; |
|---|
| 635 | } |
|---|
| 636 | return wcount; |
|---|
| 637 | } |
|---|
| 638 | |
|---|
| 639 | uint32_t AP_sequence_protein::checksum() const { |
|---|
| 640 | const AP_PROTEINS *seq = get_sequence(); |
|---|
| 641 | return GB_checksum(reinterpret_cast<const char *>(seq), sizeof(*seq)*get_sequence_length(), 0, NULp); |
|---|
| 642 | } |
|---|
| 643 | |
|---|
| 644 | int AP_sequence_protein::cmp_combined(const AP_combinableSeq *other) const { |
|---|
| 645 | const AP_sequence_protein *sother = DOWNCAST(const AP_sequence_protein*, other); |
|---|
| 646 | |
|---|
| 647 | const AP_PROTEINS *s1 = get_sequence(); |
|---|
| 648 | const AP_PROTEINS *s2 = sother->get_sequence(); |
|---|
| 649 | |
|---|
| 650 | size_t len = get_sequence_length(); |
|---|
| 651 | |
|---|
| 652 | for (size_t i = 0; i<len; ++i) { |
|---|
| 653 | int comp = long_cmp(s1[i], s2[i]); |
|---|
| 654 | if (comp) return comp; |
|---|
| 655 | } |
|---|
| 656 | |
|---|
| 657 | // ap_assert(0); // location is reached from unittests. mut1 and mut2 could be tested as well |
|---|
| 658 | return 0; |
|---|
| 659 | } |
|---|
| 660 | |
|---|