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| 1 | +/// |
| 2 | +/// Class for the analysis of distribution of APOBEC mutations |
| 3 | +/// relative to the gene expression |
| 4 | +/// |
| 5 | +Class ApobecExp.Expression [ Abstract ] |
| 6 | +{ |
| 7 | + |
| 8 | +/// Set the maximum end of genes among intersecting genes |
| 9 | +/// for using in interval tree structure |
| 10 | +ClassMethod SetGeneIntervals() |
| 11 | +{ |
| 12 | + set IndexName = "IndexGene" |
| 13 | + set chr = $order(^ApobecExp.GeneI(IndexName,"")) |
| 14 | + while (chr '= "") |
| 15 | + { |
| 16 | + set maxendpos = 0 |
| 17 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,"")) |
| 18 | + while (startpos '= "") |
| 19 | + { |
| 20 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,"")) |
| 21 | + while (endpos '= "") |
| 22 | + { |
| 23 | + set ID = $order(^ApobecExp.GeneI(IndexName,chr,startpos,endpos,"")) |
| 24 | + if (maxendpos >= startpos) { |
| 25 | + set ^ApobecExp.GeneI(IndexName,chr,startpos,endpos,ID) = maxendpos } |
| 26 | + else { |
| 27 | + set ^ApobecExp.GeneI(IndexName,chr,startpos,endpos,ID) = 0 } |
| 28 | + if (maxendpos < endpos) { |
| 29 | + set maxendpos = endpos } |
| 30 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,endpos)) |
| 31 | + } |
| 32 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos)) |
| 33 | + } |
| 34 | + set chr = $order(^ApobecExp.GeneI(IndexName,chr)) |
| 35 | + } |
| 36 | +} |
| 37 | + |
| 38 | +/// Function returns list of genes covering |
| 39 | +/// particular position on particular chromosome |
| 40 | +ClassMethod GetGeneList(chr As %String, pos As %Integer) As %Library.List |
| 41 | +{ |
| 42 | + set ret = "" |
| 43 | + set IndexName = "IndexGene" |
| 44 | + set chrI = " "_$zconvert(chr,"U") |
| 45 | + set startpos = pos |
| 46 | + if ($data(^ApobecExp.GeneI(IndexName,chrI,pos)) '= 0) { |
| 47 | + set startpos = pos } |
| 48 | + else { |
| 49 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chrI,pos),-1) } |
| 50 | + while (startpos '= "") |
| 51 | + { |
| 52 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chrI,startpos,"")) |
| 53 | + set maxend = 0 |
| 54 | + while (endpos '= "") |
| 55 | + { |
| 56 | + set ID = $order(^ApobecExp.GeneI(IndexName,chrI,startpos,endpos,"")) |
| 57 | + if (pos <= endpos) { |
| 58 | + set $list(ret,*+1) = ID } |
| 59 | + set endinterval = ^ApobecExp.GeneI(IndexName,chrI,startpos,endpos,ID) |
| 60 | + if (endinterval > maxend) { |
| 61 | + set maxend = endinterval } |
| 62 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chrI,startpos,endpos)) |
| 63 | + } |
| 64 | + set endinterval = maxend |
| 65 | + if ((endinterval = 0) || (endinterval < pos)) quit |
| 66 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chrI,startpos),-1) |
| 67 | + } |
| 68 | + return ret |
| 69 | +} |
| 70 | + |
| 71 | +/// Function returns maximum expression value among genes |
| 72 | +/// covering particular position on particular chromosome |
| 73 | +/// return: -1 if position in gene but no expression data, |
| 74 | +/// -2 if position not in gene |
| 75 | +ClassMethod GetMaxExpression(cancer As %String, sample As %String, chr As %String, pos As %Integer) |
| 76 | +{ |
| 77 | + set genelist = ..GetGeneList(chr,pos) |
| 78 | + |
| 79 | + if (genelist '= "") { |
| 80 | + set n = $listlength(genelist) } |
| 81 | + else { |
| 82 | + return (-2) } |
| 83 | + set maxexp = -1 |
| 84 | + for j=1:1:n |
| 85 | + { |
| 86 | + set GeneID = $listget(^ApobecExp.GeneD($listget(genelist,j)),2) |
| 87 | + if ($data(^exp(cancer,sample,GeneID)) '= 0) |
| 88 | + { |
| 89 | + if (maxexp < ^exp(cancer,sample,GeneID)) { |
| 90 | + set maxexp = ^exp(cancer,sample,GeneID) } |
| 91 | + } |
| 92 | + } |
| 93 | + |
| 94 | + return (maxexp) |
| 95 | +} |
| 96 | + |
| 97 | +/// Function returns expression bin number |
| 98 | +/// based on particular expression value |
| 99 | +ClassMethod GetExpressionBin(ExpressionValue As %Float) As %Integer |
| 100 | +{ |
| 101 | + if (ExpressionValue < 0) { |
| 102 | + return ExpressionValue } |
| 103 | + set leftval = $order(^expBins(ExpressionValue),-1) |
| 104 | + set rightval = $order(^expBins(leftval,"")) |
| 105 | + if ((ExpressionValue > leftval) && (ExpressionValue <= rightval)) { |
| 106 | + return (^expBins(leftval,rightval)) } |
| 107 | + else { |
| 108 | + return "" } |
| 109 | +} |
| 110 | + |
| 111 | +/// Function calculates number of APOBEC and other mutations |
| 112 | +/// relative to expression bins |
| 113 | +ClassMethod GetExpMutation() |
| 114 | +{ |
| 115 | + kill ^expResultsAPOBEC |
| 116 | + kill ^expResultsOther |
| 117 | + for i = 1:1:^cancerType |
| 118 | + { |
| 119 | + set cnt = 0 |
| 120 | + set cancer = ^cancerType(i) |
| 121 | + set sample = $order(^mutation(cancer,"")) |
| 122 | + while (sample '= "") |
| 123 | + { |
| 124 | + for j = -2:1:^expBins |
| 125 | + { |
| 126 | + set ^expResultsAPOBEC(cancer,sample,j) = 0 |
| 127 | + set ^expResultsOther(cancer,sample,j) = 0 |
| 128 | + } |
| 129 | + set chr = $order(^mutation(cancer,sample,"")) |
| 130 | + while (chr '= "") |
| 131 | + { |
| 132 | + set pos = $order(^mutation(cancer,sample,chr,"")) |
| 133 | + while (pos '= "") |
| 134 | + { |
| 135 | + set isAPOBEC = $listget(^mutation(cancer,sample,chr,pos),3) |
| 136 | + |
| 137 | + set maxexp = ..GetMaxExpression(cancer,sample,chr,pos) |
| 138 | + |
| 139 | + set expbin = ..GetExpressionBin(maxexp) |
| 140 | + |
| 141 | + if (isAPOBEC = 1) { |
| 142 | + set ^expResultsAPOBEC(cancer,sample,expbin) = ^expResultsAPOBEC(cancer,sample,expbin) + 1 } |
| 143 | + else { |
| 144 | + set ^expResultsOther(cancer,sample,expbin) = ^expResultsOther(cancer,sample,expbin) + 1 } |
| 145 | + |
| 146 | + set cnt = cnt + 1 |
| 147 | + |
| 148 | + set pos = $order(^mutation(cancer,sample,chr,pos)) |
| 149 | + } |
| 150 | + set chr = $order(^mutation(cancer,sample,chr)) |
| 151 | + } |
| 152 | + set sample = $order(^mutation(cancer,sample)) |
| 153 | + } |
| 154 | + write cancer,"=",cnt,! |
| 155 | + } |
| 156 | +} |
| 157 | + |
| 158 | +/// Function calculates and saves number of TCW motifs |
| 159 | +/// (a potential APOBEC target) in genes |
| 160 | +ClassMethod SetTCWinGenes() |
| 161 | +{ |
| 162 | + kill ^TCWinGenes |
| 163 | + set ^TCWinGenes = 0 |
| 164 | + set IndexName = "IndexGene" |
| 165 | + set chr = $order(^ApobecExp.GeneI(IndexName,"")) |
| 166 | + while (chr '= "") |
| 167 | + { |
| 168 | + #;write chr,! |
| 169 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,"")) |
| 170 | + while (startpos '= "") |
| 171 | + { |
| 172 | + #;write startpos,! |
| 173 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,"")) |
| 174 | + while (endpos '= "") |
| 175 | + { |
| 176 | + write chr," ",startpos," ",endpos,! |
| 177 | + set chrlow = $extract(chr,2,*) |
| 178 | + set chrlow = $zconvert(chrlow,"L") |
| 179 | + set chrlow = ^chrname(chrlow) |
| 180 | + |
| 181 | + if ($data(^TCW(chrlow,startpos)) '= 0) { |
| 182 | + set pos = startpos } |
| 183 | + else { |
| 184 | + set pos = $order(^TCW(chrlow,startpos)) } |
| 185 | + while ((pos '= "") && (pos <= endpos)) |
| 186 | + { |
| 187 | + set ^TCWinGenes(chrlow,pos) = "" |
| 188 | + set ^TCWinGenes = ^TCWinGenes + 1 |
| 189 | + set pos = $order(^TCW(chrlow,pos)) |
| 190 | + } |
| 191 | + |
| 192 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,endpos)) |
| 193 | + } |
| 194 | + |
| 195 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos)) |
| 196 | + } |
| 197 | + set chr = $order(^ApobecExp.GeneI(IndexName,chr)) |
| 198 | + } |
| 199 | +} |
| 200 | + |
| 201 | +/// Function calculates number of TCW motifs |
| 202 | +/// in expression bins |
| 203 | +ClassMethod GetExpTCW() |
| 204 | +{ |
| 205 | + //kill ^expTCW |
| 206 | + for i = 1:1:^cancerType |
| 207 | + { |
| 208 | + set cancer = ^cancerType(i) |
| 209 | + set sample = $order(^mutation(cancer,"")) |
| 210 | + while (sample '= "") |
| 211 | + { |
| 212 | + if ($data(^expTCW(cancer,sample,0)) '= 0) |
| 213 | + { |
| 214 | + write cancer," ",sample," Done",! |
| 215 | + set sample = $order(^mutation(cancer,sample)) |
| 216 | + continue |
| 217 | + } |
| 218 | + for j = -2:1:7 { |
| 219 | + set ^expTCW(cancer,sample,j) = 0 } |
| 220 | + set chr = $order(^TCWinGenes("")) |
| 221 | + while (chr '= "") |
| 222 | + { |
| 223 | + set cnt = 0 |
| 224 | + set pos = $order(^TCWinGenes(chr,"")) |
| 225 | + while (pos '= "") |
| 226 | + { |
| 227 | + set maxexp = ..GetMaxExpression(cancer,sample,chr,pos) |
| 228 | + set expbin = ..GetExpressionBin(maxexp) |
| 229 | + set ^expTCW(cancer,sample,expbin) = ^expTCW(cancer,sample,expbin) + 1 |
| 230 | + set cnt = cnt + 1 |
| 231 | + |
| 232 | + set pos = $order(^TCWinGenes(chr,pos)) |
| 233 | + } |
| 234 | + write chr," ",cnt,! |
| 235 | + set chr = $order(^TCWinGenes(chr)) |
| 236 | + } |
| 237 | + |
| 238 | + write cancer," ",sample,! |
| 239 | + set sample = $order(^mutation(cancer,sample)) |
| 240 | + } |
| 241 | + } |
| 242 | +} |
| 243 | + |
| 244 | +/// Function calculates number of bases |
| 245 | +/// in expression bins |
| 246 | +ClassMethod GetExpAll() |
| 247 | +{ |
| 248 | + //kill ^expAll |
| 249 | + |
| 250 | + for i = 1:1:^cancerType |
| 251 | + { |
| 252 | + set cancer = ^cancerType(i) |
| 253 | + set sample = $order(^mutation(cancer,"")) |
| 254 | + while (sample '= "") |
| 255 | + { |
| 256 | + if ($data(^expAll(cancer,sample,0)) '= 0) |
| 257 | + { |
| 258 | + write cancer," ",sample," Done",! |
| 259 | + set sample = $order(^mutation(cancer,sample)) |
| 260 | + continue |
| 261 | + } |
| 262 | + for j = -2:1:7 { |
| 263 | + set ^expAll(cancer,sample,j) = 0 } |
| 264 | + write cancer," ",sample,! |
| 265 | + |
| 266 | + write "Interval part",! |
| 267 | + set chr = $order(^geneNonoverlap("")) |
| 268 | + while (chr '= "") |
| 269 | + { |
| 270 | + set startpos = $order(^geneNonoverlap(chr,"")) |
| 271 | + while (startpos '= "") |
| 272 | + { |
| 273 | + set endpos = $order(^geneNonoverlap(chr,startpos,"")) |
| 274 | + while (endpos '= "") |
| 275 | + { |
| 276 | + set pos = startpos |
| 277 | + set maxexp = ..GetMaxExpression(cancer,sample,chr,pos) |
| 278 | + set expbin = ..GetExpressionBin(maxexp) |
| 279 | + set ^expAll(cancer,sample,expbin) = ^expAll(cancer,sample,expbin) + (endpos - startpos + 1) |
| 280 | + |
| 281 | + set endpos = $order(^geneNonoverlap(chr,startpos,endpos)) |
| 282 | + } |
| 283 | + set startpos = $order(^geneNonoverlap(chr,startpos)) |
| 284 | + } |
| 285 | + set chr = $order(^geneNonoverlap(chr)) |
| 286 | + } |
| 287 | + |
| 288 | + write "Overlapped part",! |
| 289 | + set chr = $order(^geneOverlap("")) |
| 290 | + while (chr '= "") |
| 291 | + { |
| 292 | + set pos = $order(^geneOverlap(chr,"")) |
| 293 | + while (pos '= "") |
| 294 | + { |
| 295 | + set maxexp = ..GetMaxExpression(cancer,sample,chr,pos) |
| 296 | + set expbin = ..GetExpressionBin(maxexp) |
| 297 | + set ^expAll(cancer,sample,expbin) = ^expAll(cancer,sample,expbin) + 1 |
| 298 | + set pos = $order(^geneOverlap(chr,pos)) |
| 299 | + } |
| 300 | + set chr = $order(^geneOverlap(chr)) |
| 301 | + } |
| 302 | + |
| 303 | + write cancer," ",sample,! |
| 304 | + set sample = $order(^mutation(cancer,sample)) |
| 305 | + } |
| 306 | + } |
| 307 | +} |
| 308 | + |
| 309 | +/// Function divide DNA positions covering by genes |
| 310 | +/// into intervals covered by only single gene |
| 311 | +/// and intervals covered by multiple genes. |
| 312 | +/// Results are saved in globals. |
| 313 | +ClassMethod DivideGenesIntoIntervals() |
| 314 | +{ |
| 315 | + kill ^geneNonoverlap |
| 316 | + set ^geneNonoverlap = 0 |
| 317 | + kill ^geneOverlap |
| 318 | + set ^geneOverlap = 0 |
| 319 | + set IndexName = "IndexGene" |
| 320 | + set chr = $order(^ApobecExp.GeneI(IndexName,"")) |
| 321 | + while (chr '= "") |
| 322 | + { |
| 323 | + set chrlow = $zconvert($extract(chr,2,*),"L") |
| 324 | + set chrlow = ^chrname(chrlow) |
| 325 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,"")) |
| 326 | + while (startpos '= "") |
| 327 | + { |
| 328 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,"")) |
| 329 | + while (endpos '= "") |
| 330 | + { |
| 331 | + set prevn = 0 |
| 332 | + for i = startpos:1:endpos |
| 333 | + { |
| 334 | + set genelist = ..GetGeneList(chrlow,i) |
| 335 | + |
| 336 | + if (genelist '= "") { |
| 337 | + set n = $listlength(genelist) } |
| 338 | + else { |
| 339 | + set n = 0 } |
| 340 | + |
| 341 | + if (n = 0) |
| 342 | + { |
| 343 | + write "error: no gene, chr=",chrlow,", pos=",i,! |
| 344 | + return |
| 345 | + } |
| 346 | + elseif (n > 1) |
| 347 | + { |
| 348 | + set ^geneOverlap(chrlow,i) = "" |
| 349 | + set ^geneOverlap = ^geneOverlap + 1 |
| 350 | + if (prevn = 1) |
| 351 | + { |
| 352 | + set ^geneNonoverlap(chrlow,istart,iend) = "" |
| 353 | + set ^geneNonoverlap = ^geneNonoverlap + 1 |
| 354 | + } |
| 355 | + set prevn = 2 |
| 356 | + } |
| 357 | + elseif(n = 1) |
| 358 | + { |
| 359 | + if (prevn = 1) |
| 360 | + { |
| 361 | + set iend = iend + 1 |
| 362 | + if (iend '= i) |
| 363 | + { |
| 364 | + write "error: iend '= i, chr=",chr,", startpos=",startpos,", endpos=",endpos,! |
| 365 | + return 0 |
| 366 | + } |
| 367 | + if (i = endpos) |
| 368 | + { |
| 369 | + set ^geneNonoverlap(chrlow,istart,iend) = "" |
| 370 | + set ^geneNonoverlap = ^geneNonoverlap + 1 |
| 371 | + set prevn = 0 |
| 372 | + } |
| 373 | + } |
| 374 | + else |
| 375 | + { |
| 376 | + set istart = i |
| 377 | + set iend = i |
| 378 | + } |
| 379 | + set prevn = 1 |
| 380 | + } |
| 381 | + } |
| 382 | + |
| 383 | + set endpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos,endpos)) |
| 384 | + } |
| 385 | + set startpos = $order(^ApobecExp.GeneI(IndexName,chr,startpos)) |
| 386 | + } |
| 387 | + write chr,! |
| 388 | + set chr = $order(^ApobecExp.GeneI(IndexName,chr)) |
| 389 | + } |
| 390 | +} |
| 391 | + |
| 392 | +} |
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