_:b558137173 "2"^^ . _:b558137172 "2"^^ . _:b558137820 . . _:b558137175 "2"^^ . . _:b558137174 "2"^^ . _:b558137310 . _:b558136879 . . _:b558137096 . _:b558137169 "2"^^ . . _:b558137559 . . _:b558137168 "2"^^ . _:b558137171 "2"^^ . . _:b558137170 "2"^^ . _:b558137181 "2"^^ . . _:b558137180 "2"^^ . _:b558137158 . _:b558137183 "2"^^ . . _:b558136510 . _:b558136802 . _:b558137182 "2"^^ . _:b558137335 . _:b558137177 "2"^^ . . _:b558137374 . . _:b558137176 "2"^^ . _:b558137536 . _:b558137126 . _:b558137179 "2"^^ . . . _:b558136437 . _:b558137015 . _:b558137178 "2"^^ . . _:b558137133 . . . _:b558137189 "2"^^ . _:b558137154 . _:b558137188 "2"^^ . . . _:b558137191 "2"^^ . . _:b558137190 "2"^^ . . _:b558137185 "2"^^ . _:b558137241 . . _:b558137184 "2"^^ . _:b558137977 . _:b558136368 . _:b558137187 "2"^^ . . _:b558137299 . _:b558137186 "2"^^ . . . _:b558137197 "2"^^ . _:b558137551 . _:b558138134 . _:b558137102 . _:b558137196 "2"^^ . . _:b558137199 "2"^^ . . . . _:b558136243 . _:b558137816 . _:b558137198 "2"^^ . _:b558137193 "2"^^ . . _:b558137192 "2"^^ . _:b558136321 . _:b558137195 "2"^^ . _:b558137013 . . _:b558137120 . _:b558137194 "2"^^ . . _:b33179882 . . _:b558137844 . _:b558137827 . _:b558137205 "2"^^ . _:b558137533 . . _:b558137204 "2"^^ . _:b558137207 "2"^^ . . _:b558137206 "2"^^ . _:b558137669 . _:b558137004 . _:b558137201 "2"^^ . _:b558136905 . _:b558137582 . _:b558137200 "2"^^ . _:b558136517 . . . _:b558137203 "2"^^ . _:b558137804 . _:b558137202 "2"^^ . . _:b558137213 "2"^^ . _:b558137212 "2"^^ . _:b558137215 "2"^^ . _:b558137214 "2"^^ . _:b558138147 . . _:b558137209 "2"^^ . _:b558137208 "2"^^ . _:b558137509 . _:b558136937 . _:b558137211 "2"^^ . _:b558136751 . _:b558137210 "2"^^ . . _:b558137221 "2"^^ . _:b558136738 . _:b558137220 "2"^^ . _:b558136383 . _:b558137447 . _:b558137223 "2"^^ . _:b558137379 . _:b558137222 "2"^^ . _:b558137799 . _:b558137217 "2"^^ . _:b558137216 "2"^^ . _:b558137700 . . _:b558137759 . . _:b558137219 "2"^^ . _:b558136714 . . . . _:b558137218 "2"^^ . _:b558136977 . _:b558136596 . . _:b558137160 . _:b558137229 "2"^^ . . _:b558136995 . _:b558136683 . _:b558137228 "2"^^ . _:b558137231 "2"^^ . . . _:b558137230 "2"^^ . _:b558137225 "2"^^ . _:b558137224 "2"^^ . . . _:b558137227 "2"^^ . _:b558137783 . _:b558137226 "2"^^ . . _:b558137237 "2"^^ . . _:b558136354 . . _:b558138009 . _:b558137236 "2"^^ . . _:b558137239 "2"^^ . _:b558138029 . . _:b558137238 "2"^^ . _:b558136333 . _:b558137233 "2"^^ . _:b558136663 . _:b558137397 . . _:b558136639 . _:b558137232 "2"^^ . . _:b558137261 . _:b558137235 "2"^^ . _:b558136464 . _:b558137094 . _:b558137234 "2"^^ . _:b558136573 . _:b558137245 "2"^^ . . _:b558137244 "2"^^ . _:b558136889 . _:b558137247 "2"^^ . _:b558136951 . _:b33179869 "We evaluated coverage uniformity using Lorenz curves20 which showed highly uniform coverage, representing a major improvement over our previous SNS method11,18 and is equivalent to the MALBAC data>>19<< (Fig. 1d). Next, we calculated error rates, including the allelic dropout rate (ADR) and false positive rate (FPR) by comparing single cell variants to the population data (Methods). Our analysis suggests that Nuc-Seq generates low" . _:b558136426 . _:b558136691 . _:b558137246 "2"^^ . _:b558138023 . . _:b558137806 . _:b558137241 "2"^^ . _:b558137115 . _:b558137240 "2"^^ . _:b558137000 . _:b558137243 "2"^^ . _:b558137967 . _:b558137242 "2"^^ . _:b558136352 . _:b558137253 "2"^^ . _:b558137672 . . _:b558137252 "2"^^ . . . _:b558137255 "2"^^ . . _:b558137254 "2"^^ . . _:b558137249 "2"^^ . _:b558137562 . _:b558137248 "2"^^ . _:b558137251 "2"^^ . _:b558136656 . _:b558136748 . _:b558137250 "2"^^ . _:b558137093 . . _:b558137092 . _:b558137261 "2"^^ . _:b558136335 . _:b558137095 . _:b558137260 "2"^^ . . _:b558137263 "2"^^ . _:b558137094 . _:b558136339 . _:b558137445 . _:b558137828 . _:b558137089 . _:b558137262 "2"^^ . _:b558137609 . _:b558137088 . _:b558137257 "2"^^ . _:b558136960 . _:b558137091 . _:b558137256 "2"^^ . _:b558136881 . . _:b558137259 "2"^^ . _:b558137090 . . _:b558137673 . _:b558137101 . _:b558137258 "2"^^ . _:b558137100 . _:b558137269 "2"^^ . _:b558136356 . _:b558137103 . _:b558137268 "2"^^ . . _:b558137271 "2"^^ . _:b558137102 . _:b558137097 . _:b558137270 "2"^^ . _:b558137878 . _:b558137096 . _:b558137265 "2"^^ . . _:b558137778 . _:b558137099 . _:b558137264 "2"^^ . . _:b558137518 . _:b558137098 . _:b558137267 "2"^^ . . _:b558137109 . _:b558137359 . _:b558137266 "2"^^ . _:b558137272 . . _:b558137277 "2"^^ . _:b558137108 . . _:b558136536 . _:b558137583 . . _:b558137276 "2"^^ . _:b558137111 . _:b558136988 . _:b558137939 . _:b558137110 . _:b558137279 "2"^^ . . _:b558137278 "2"^^ . _:b558137105 . _:b558137903 . _:b558137623 . _:b558137104 . _:b558137273 "2"^^ . . . _:b558137107 . _:b558137272 "2"^^ . _:b558137106 . _:b558137275 "2"^^ . . _:b558137117 . _:b558137274 "2"^^ . . _:b558137116 . _:b558137285 "2"^^ . . _:b558137119 . _:b558137284 "2"^^ . . . _:b558137287 "2"^^ . _:b558137118 . . _:b558136792 . _:b558137286 "2"^^ . _:b558137113 . . . _:b558137281 "2"^^ . _:b558137112 . . . _:b558136617 . _:b558137115 . _:b558137280 "2"^^ . _:b558137862 . _:b558136253 . _:b558136574 . _:b558137283 "2"^^ . _:b558137114 . . _:b558137125 . _:b558137282 "2"^^ . . _:b558137124 . _:b558137293 "2"^^ . _:b558137151 . . _:b558137127 . _:b558137292 "2"^^ . _:b558136425 . . _:b558137453 . _:b558137126 . _:b558137295 "2"^^ . _:b558136246 . . _:b558138095 . . _:b558137294 "2"^^ . _:b558137121 . _:b558137120 . _:b558137289 "2"^^ . . _:b558137123 . _:b558137288 "2"^^ . _:b558137122 . _:b558137291 "2"^^ . _:b558137642 . . _:b558137290 "2"^^ . _:b558137133 . _:b558136774 . _:b558137332 . . _:b558137132 . _:b558137301 "2"^^ . _:b558138071 . _:b558136541 . _:b558137300 "2"^^ . _:b558137135 . . _:b558137040 . . _:b558137303 "2"^^ . _:b558137134 . . _:b558136282 . _:b558137302 "2"^^ . _:b558137129 . _:b558137128 . _:b558137297 "2"^^ . _:b558136248 . _:b558137296 "2"^^ . _:b558137131 . _:b558136716 . _:b558137130 . _:b558137299 "2"^^ . _:b558137141 . _:b558138133 . _:b558137298 "2"^^ . _:b558137955 . _:b558137140 . _:b558137309 "2"^^ . _:b558136654 . _:b558138047 . . _:b558137143 . _:b558137308 "2"^^ . _:b558137142 . _:b558137311 "2"^^ . . _:b558137310 "2"^^ . _:b558137137 . _:b558137430 . _:b33179875 "2c, Supplementary Information). PIK3CA is the most common driver mutation in luminal A breast cancers7,>>9<<." . . _:b558137305 "2"^^ . _:b558137136 . . _:b558136946 . _:b558137304 "2"^^ . _:b558137139 . . _:b558137307 "2"^^ . _:b558137138 . _:b558137454 . _:b558136496 . _:b558137149 . _:b558138067 . _:b558137306 "2"^^ . _:b558137148 . _:b558137317 "2"^^ . . _:b558137151 . _:b558137316 "2"^^ . _:b558137150 . _:b558137319 "2"^^ . . _:b558137947 . _:b558137145 . _:b558137318 "2"^^ . _:b558137144 . _:b558137313 "2"^^ . _:b558136477 . . _:b558137147 . _:b558137312 "2"^^ . . . _:b558137119 . _:b558137146 . _:b558137315 "2"^^ . . . _:b558137314 "2"^^ . _:b558137157 . . _:b558137325 "2"^^ . _:b558137156 . _:b558137159 . _:b558137324 "2"^^ . _:b558136939 . _:b558137327 "2"^^ . _:b558137158 . _:b558137153 . _:b558137326 "2"^^ . _:b558136836 . _:b558136634 . . _:b558137321 "2"^^ . _:b558137152 . . _:b558137446 . _:b558137155 . _:b558137320 "2"^^ . . _:b558137020 . _:b558137154 . _:b558137323 "2"^^ . _:b558136293 . . _:b558137165 . _:b558137322 "2"^^ . _:b558137164 . _:b558137333 "2"^^ . . _:b558137332 "2"^^ . _:b558137167 . _:b558137092 . _:b558137763 . _:b558136734 . _:b558137166 . _:b558137335 "2"^^ . . _:b558137161 . _:b558137334 "2"^^ . _:b558137421 . _:b558137160 . _:b558137329 "2"^^ . _:b558137163 . _:b558137328 "2"^^ . . _:b558137138 . . _:b558137162 . _:b558137722 . _:b558137331 "2"^^ . . _:b558137173 . _:b558137330 "2"^^ . _:b558137311 . . _:b558136706 . _:b558137341 "2"^^ . _:b558137172 . _:b558136286 . _:b558137175 . _:b558137340 "2"^^ . _:b558136430 . _:b558137174 . _:b558137608 . _:b558137343 "2"^^ . _:b558137169 . _:b558137342 "2"^^ . _:b558137918 . _:b558137998 . _:b558136270 . _:b558137337 "2"^^ . _:b558137168 . _:b558136869 . _:b558137171 . _:b558137336 "2"^^ . _:b558137661 . _:b558136256 . _:b558137170 . _:b558137339 "2"^^ . _:b558137003 . _:b558137510 . _:b558137181 . _:b558137338 "2"^^ . . _:b558138013 . _:b558137180 . _:b558136327 "13"^^ . _:b558137183 . _:b558136326 "13"^^ . _:b558137596 . _:b558137182 . . _:b558136325 "13"^^ . _:b558137177 . _:b558136324 "13"^^ . . _:b558137176 . _:b558136323 "13"^^ . _:b33179847 "This model has also been supported by bulk sequencing data in prostate cancer29 and in rearrangement patterns called firestorms>>30<< or chromothripsis31." . _:b558137179 . . _:b558136842 . . _:b558136322 "13"^^ . . _:b558137178 . . _:b558136321 "13"^^ . _:b558137189 . _:b558136320 "13"^^ . _:b558137188 . _:b558136335 "13"^^ . _:b558137191 . _:b558137485 . _:b558136334 "13"^^ . . _:b33179856 "Our data also has important implications for the mutator phenotype, which posits that tumor evolution is driven by increased mutation rates34,>>38<<. While TCGA studies39\u201341 report increased mutation frequencies, it remains unclear whether these mutations accumulate over many cell divisions (at a normal error rate) or through an increased mutation rate. Our TNBC data suggest an" . _:b558137190 . _:b558136333 "13"^^ . . _:b558137185 . _:b558137218 . _:b558136332 "13"^^ . _:b558137184 . _:b558137725 . _:b558136331 "13"^^ . _:b558137187 . _:b558136330 "13"^^ . _:b558137186 . _:b558137166 . _:b558136329 "13"^^ . _:b558137197 . _:b558138027 . _:b558136328 "13"^^ . _:b558137196 . _:b558137255 . _:b558136308 . _:b558136343 "12"^^ . _:b558137199 . . . _:b558136342 "12"^^ . . _:b558137198 . _:b558136341 "12"^^ . _:b558137193 . _:b33179851 "In contrast, point mutations occur through defects in DNA repair or replication machinery>>34<<, which accumulate more gradually over many cell divisions." . _:b558137975 . _:b558136340 "12"^^ . _:b558137192 . _:b558137701 . . _:b558136339 "12"^^ . _:b558137195 . _:b558136338 "12"^^ . _:b558137602 . _:b558137576 . _:b558137605 . _:b558137692 . . _:b558137194 . _:b558136337 "12"^^ . . _:b558136275 . _:b558137205 . _:b558136336 "12"^^ . _:b558137204 . _:b558136351 "11"^^ . _:b558137207 . _:b558136350 "11"^^ . _:b558137364 . _:b558137206 . . _:b558137888 . . _:b558136349 "12"^^ . _:b558137201 . . _:b558136348 "12"^^ . . _:b558137200 . _:b558137099 . _:b558136347 "12"^^ . _:b558138142 . _:b558137476 . _:b558137203 . _:b558136346 "12"^^ . _:b558136454 . _:b558137202 . _:b558136345 "12"^^ . _:b558137213 . _:b558137349 . . _:b558136344 "12"^^ . . _:b558137212 . _:b558136359 "11"^^ . _:b558137215 . _:b558136590 . _:b558136358 "11"^^ . . _:b558137214 . _:b33179848 . _:b558137938 . _:b558136357 "11"^^ . _:b558137209 . _:b558136356 "11"^^ . _:b558137025 . _:b558137208 . . _:b558136355 "11"^^ . . _:b558137211 . _:b558136354 "11"^^ . _:b558136392 . _:b558137210 . . _:b558136353 "11"^^ . . _:b558137221 . _:b558136969 . _:b558136352 "11"^^ . _:b558136367 "10"^^ . _:b558137220 . . _:b558136366 "10"^^ . _:b558137223 . . _:b558137250 . _:b558136365 "10"^^ . _:b33179847 . _:b558137222 . _:b558136992 . _:b558136364 "10"^^ . _:b558137217 . _:b558137216 . _:b558136363 "11"^^ . . _:b558137219 . _:b558136362 "11"^^ . . _:b558137218 . _:b558136361 "11"^^ . _:b558137229 . _:b558136360 "11"^^ . _:b558136375 "10"^^ . _:b558137228 . _:b558136374 "10"^^ . _:b558137231 . _:b558137565 . _:b558137698 . _:b558136373 "10"^^ . _:b558137230 . . _:b558136372 "10"^^ . _:b558137225 . _:b558137789 . _:b558136371 "10"^^ . _:b558137224 . . _:b558137929 . _:b558136370 "10"^^ . _:b558137227 . . _:b558136369 "10"^^ . _:b558137619 . _:b558137226 . . _:b558136368 "10"^^ . _:b558137252 . _:b558137237 . . _:b558137336 . _:b558137236 . . . _:b558136382 "9"^^ . _:b558137239 . _:b558136828 . _:b33179862 "four (or more) copies of each single cell genome for whole-genome-amplification (WGA) to decrease the allelic dropout and false positive error rates, which are major sources of error during multiple-displacement-amplification (MDA)14,>>15<<. Additionally, we limit the MDA time to 80 minutes to mitigate FP errors associated with the infidelity of the \u03D529 polymerase (Supplementary Methods)." . _:b558136383 "9"^^ . _:b558136381 "10"^^ . _:b558137238 . . _:b558136380 "10"^^ . _:b558137233 . . _:b558136290 . . _:b558136515 . _:b558136379 "10"^^ . _:b558137232 . _:b558137201 . _:b33179874 "2c, Supplementary Information). PIK3CA is the most common driver mutation in luminal A breast cancers>>7<<,9." . _:b558136378 "10"^^ . _:b558137235 . _:b558136377 "10"^^ . _:b558137234 . _:b558137056 . _:b558136376 "10"^^ . _:b558137245 . . _:b558137244 . _:b558136390 "9"^^ . . _:b558137247 . . . _:b558136441 . _:b558136391 "9"^^ . _:b558136265 . _:b558137246 . . . _:b558136763 . _:b558136388 "9"^^ . _:b558137241 . _:b558136782 . _:b558136389 "9"^^ . _:b558136932 . _:b558137240 . . _:b558136386 "9"^^ . . _:b558136480 . _:b558137243 . _:b558136387 "9"^^ . . _:b558137242 . _:b558137475 . . _:b558136384 "9"^^ . _:b558136710 . _:b558137253 . . _:b558136385 "9"^^ . _:b558137252 . _:b558137840 . _:b558137886 . _:b558136398 "9"^^ . _:b558137255 . . _:b558137084 . _:b558136399 "9"^^ . _:b558137254 . _:b558136396 "9"^^ . _:b558138087 . _:b558137249 . . _:b33179859 . _:b558136397 "9"^^ . _:b558136848 . _:b558136775 . . . _:b558137248 . _:b558136394 "9"^^ . . _:b558137251 . . _:b558136395 "9"^^ . _:b558137250 . _:b558137264 . _:b558136392 "9"^^ . _:b558137261 . _:b558137507 . _:b558136393 "9"^^ . _:b558137260 . . _:b558136406 "8"^^ . _:b558137870 . _:b558136689 . . _:b558137263 . _:b558136924 . _:b558136407 "8"^^ . . _:b558137262 . _:b558137656 . _:b558136404 "8"^^ . _:b558137257 . _:b558136660 . _:b558136405 "8"^^ . . _:b558137838 . _:b558137256 . . _:b558136402 "9"^^ . . _:b558137259 . . _:b558136403 "8"^^ . _:b558137258 . _:b558137942 . . . _:b558136400 "9"^^ . _:b558137269 . . _:b558136401 "9"^^ . _:b558137268 . _:b558136414 "8"^^ . _:b558138036 . _:b558137271 . _:b558136415 "8"^^ . . . _:b558137270 . _:b558136412 "8"^^ . _:b558136384 . _:b558137265 . _:b558136413 "8"^^ . . _:b558137264 . _:b558136410 "8"^^ . _:b558136315 . . . _:b558137267 . _:b558136411 "8"^^ . _:b558137266 . . _:b558136408 "8"^^ . _:b558137203 . . _:b558137277 . . _:b558136409 "8"^^ . _:b558138011 . . _:b558137276 . . _:b558136422 "8"^^ . _:b558137279 . _:b558136423 "8"^^ . . . _:b558137278 . _:b558136420 "8"^^ . . . _:b558137273 . _:b558136421 "8"^^ . . _:b558137272 . _:b558136418 "8"^^ . _:b558137275 . _:b558136419 "8"^^ . _:b558137274 . _:b558137330 . . _:b558136416 "8"^^ . _:b558137285 . _:b558136417 "8"^^ . . _:b558137284 . _:b558136430 "8"^^ . . . _:b558136363 . _:b558137287 . _:b558136431 "8"^^ . _:b558137286 . _:b558137307 . _:b558136428 "8"^^ . _:b558137281 . _:b558136429 "8"^^ . . _:b558138141 . _:b558137280 . . _:b558137809 . _:b558136426 "8"^^ . _:b558137283 . _:b558136427 "8"^^ . _:b558136414 . _:b558136870 . _:b558137282 . _:b558136424 "8"^^ . _:b558137461 . _:b558137293 . _:b558136425 "8"^^ . _:b558137292 . _:b558136438 "8"^^ . . _:b558136861 . _:b558137295 . _:b558136439 "8"^^ . _:b558137294 . . . _:b558136436 "8"^^ . _:b558137822 . _:b558137864 . _:b558137289 . _:b558136437 "8"^^ . . _:b558137288 . _:b558136434 "8"^^ . _:b33179880 "Many of the subclonal mutations (23.44%) were predicted to damage protein function by both POLYPHEN21 and SIFT>>22<< (Extended Data Fig." . . _:b558137188 . _:b558137291 . _:b558136435 "8"^^ . _:b558136947 . . _:b558137290 . . _:b558136432 "8"^^ . . _:b558137301 . _:b558136433 "8"^^ . _:b558136838 . _:b558137300 . _:b558136446 "7"^^ . . _:b558136776 . _:b558137303 . _:b558136447 "7"^^ . _:b558136455 . _:b558137302 . . _:b558136444 "7"^^ . . . _:b558136677 . _:b558137297 . _:b558136445 "7"^^ . . _:b558137296 . _:b558136442 "8"^^ . . _:b558137299 . _:b558136443 "8"^^ . _:b558137298 . _:b558136440 "8"^^ . . . . _:b558137309 . _:b558136441 "8"^^ . _:b558137308 . _:b558136454 "7"^^ . . . _:b558137311 . _:b558136455 "7"^^ . _:b558137204 . _:b558137310 . _:b558136452 "7"^^ . _:b558137111 . _:b558137305 . _:b558136453 "7"^^ . _:b558137304 . _:b558136450 "7"^^ . _:b558137307 . _:b558136451 "7"^^ . . _:b558138167 . _:b558137306 . _:b558136448 "7"^^ . _:b558137718 . _:b558137317 . _:b558136449 "7"^^ . _:b558137598 . . _:b558137316 . _:b558136462 "7"^^ . _:b558138079 . . _:b558137319 . _:b33179876 "To investigate copy number diversity, we performed SNS11,>>18<< on 50 single nuclei. We constructed a neighbor-joining tree, which showed that single tumor cells shared highly similar CNAs (mean R2= 0.89), representing a monoclonal population (Fig." . _:b558137484 . _:b558136463 "7"^^ . _:b558137318 . _:b558136460 "7"^^ . _:b558137313 . _:b558136461 "7"^^ . . . _:b558137312 . _:b558136458 "7"^^ . _:b558137315 . _:b558136459 "7"^^ . _:b558136945 . . _:b558138144 . _:b558137314 . _:b558136456 "7"^^ . _:b558136959 . _:b558137546 . _:b558137325 . _:b558137991 . _:b558136457 "7"^^ . _:b558137324 . _:b558136470 "7"^^ . . _:b558136529 . _:b558137327 . _:b558136471 "7"^^ . _:b558137926 . _:b558136442 . _:b558138154 . _:b558137326 . _:b558136468 "7"^^ . _:b558136986 . _:b558137321 . _:b558136469 "7"^^ . _:b558136692 . _:b558137320 . _:b558136466 "7"^^ . _:b558137323 . _:b558136467 "7"^^ . _:b558137450 . _:b558136495 . _:b558137322 . _:b558136464 "7"^^ . . _:b558137333 . _:b558136465 "7"^^ . _:b558137394 . . _:b558137332 . _:b558136478 "7"^^ . . _:b558137335 . _:b558136479 "7"^^ . _:b558136358 . . _:b558137334 . _:b558136476 "7"^^ . . _:b558137329 . _:b558136477 "7"^^ . _:b558136820 . . _:b558137328 . _:b558136474 "7"^^ . _:b558136858 . _:b558137331 . _:b558136475 "7"^^ . . . _:b558137330 . _:b558136472 "7"^^ . _:b558137341 . _:b558136473 "7"^^ . . . _:b558137340 . _:b558136486 "7"^^ . . _:b558137343 . _:b558136487 "7"^^ . . _:b558137342 . _:b558136484 "7"^^ . . _:b558137337 . _:b558136485 "7"^^ . _:b558136668 . _:b558137336 . _:b558136482 "7"^^ . _:b558136815 . . _:b558137339 . _:b558136483 "7"^^ . _:b558137338 . _:b558138070 . _:b558136480 "7"^^ . . _:b558137220 . . _:b558137906 . _:b558136837 . _:b558136481 "7"^^ . . _:b558138075 . . _:b558136836 . _:b558136494 "7"^^ . . _:b558136495 "6"^^ . _:b558136839 . _:b558136838 . _:b558136408 . _:b558136492 "7"^^ . _:b558137691 . . _:b558136833 . _:b558136493 "7"^^ . . _:b558136832 . _:b558136490 "7"^^ . . . . _:b558136835 . . _:b558136491 "7"^^ . _:b558136562 . _:b558136834 . _:b558136488 "7"^^ . . . _:b558137706 . _:b558136845 . _:b558136489 "7"^^ . . _:b558136502 "6"^^ . _:b558136844 . _:b558136701 . _:b558136424 . _:b558136503 "6"^^ . _:b558136847 . . _:b558136514 . _:b558136893 . _:b558136500 "6"^^ . _:b558137603 . _:b558136846 . _:b558137745 . _:b558136501 "6"^^ . _:b558136841 . _:b558137810 . _:b558136498 "6"^^ . _:b558136840 . . . _:b558136499 "6"^^ . _:b558136843 . _:b558138120 . _:b558136496 "6"^^ . _:b558136842 . . . _:b558136497 "6"^^ . _:b558138112 . _:b558136853 . . _:b558136510 "6"^^ . _:b558136852 . _:b558136511 "6"^^ . . _:b558136855 . _:b558136578 . . _:b558137997 . . _:b558136854 . . _:b558136508 "6"^^ . . _:b558137210 . _:b558136509 "6"^^ . _:b558136849 . _:b558136367 . _:b558136506 "6"^^ . _:b558138073 . _:b558136848 . _:b558136507 "6"^^ . _:b558137735 . _:b558136851 . _:b558136909 . _:b558136504 "6"^^ . _:b558136850 . _:b558136295 . _:b558136505 "6"^^ . _:b558136861 . . . . _:b558136518 "6"^^ . _:b558136860 . . _:b558136633 . _:b558136519 "6"^^ . _:b558136863 . _:b558136322 . . _:b558136516 "6"^^ . _:b558136862 . . _:b558136581 . _:b558136857 . _:b558136517 "6"^^ . . _:b558136514 "6"^^ . _:b558136856 . _:b558138140 . _:b558136515 "6"^^ . _:b558136859 . _:b558137300 . _:b558136512 "6"^^ . _:b558136858 . _:b558136513 "6"^^ . _:b558136869 . _:b558136526 "6"^^ . _:b558136868 . _:b558136606 . . . _:b558136781 . _:b558136527 "6"^^ . _:b558136871 . . _:b558136524 "6"^^ . _:b558136870 . . _:b558136525 "6"^^ . _:b558138164 . _:b558137432 . _:b558136865 . _:b558136522 "6"^^ . _:b558137983 . _:b558136864 . . . _:b558137425 . _:b558136523 "6"^^ . _:b558137317 . _:b558136867 . _:b558137438 . _:b558136520 "6"^^ . _:b558136866 . . _:b558136919 . _:b558136623 . _:b558136521 "6"^^ . _:b558136877 . _:b558136534 "6"^^ . _:b558136876 . _:b558136535 "6"^^ . _:b558136879 . . _:b558136719 . _:b558137124 . _:b558136532 "6"^^ . _:b558137961 . _:b558136878 . . . _:b558136533 "6"^^ . _:b558137856 . _:b558136873 . _:b558136530 "6"^^ . _:b558136872 . . _:b558136531 "6"^^ . _:b558136875 . _:b558136528 "6"^^ . _:b558136874 . . . _:b558136529 "6"^^ . _:b558136885 . . . _:b558137927 . _:b558136825 . . _:b558136884 . _:b558136542 "6"^^ . _:b558136543 "6"^^ . _:b558136887 . _:b558136540 "6"^^ . _:b558136886 . . _:b558136541 "6"^^ . _:b558136881 . _:b558136538 "6"^^ . _:b558137128 . _:b558136880 . _:b558136539 "6"^^ . _:b558136883 . _:b558136536 "6"^^ . _:b558136882 . _:b558137143 . _:b558136537 "6"^^ . _:b558137610 . _:b558136893 . _:b558136550 "6"^^ . _:b558136892 . . _:b558137021 . _:b558136674 . _:b558136551 "6"^^ . _:b558136895 . _:b558136548 "6"^^ . _:b558136894 . _:b558136549 "6"^^ . _:b558136889 . _:b558136580 . _:b558136729 . _:b558136546 "6"^^ . _:b558137768 . _:b558136888 . _:b558136547 "6"^^ . _:b558136891 . _:b558136544 "6"^^ . _:b558136890 . . _:b558137042 . _:b558138117 . . _:b558136545 "6"^^ . _:b558136901 . . . . _:b558137338 . _:b558136900 . _:b558136557 "5"^^ . _:b558136903 . _:b558136556 "5"^^ . _:b558136251 . _:b558136902 . . _:b558137757 . _:b558137181 . _:b558136559 "5"^^ . _:b558136897 . . _:b558137653 . _:b558136558 "5"^^ . _:b558137039 . . _:b558136896 . _:b558136553 "5"^^ . _:b558136899 . . _:b558136552 "6"^^ . . _:b558136898 . . _:b558136555 "5"^^ . _:b558136909 . _:b558136554 "5"^^ . _:b558137564 . _:b558136908 . _:b558137565 . _:b558136857 . _:b558137566 . _:b558137567 . _:b558136565 "5"^^ . _:b558137560 . _:b558136542 . _:b558136911 . _:b558137561 . . _:b558137562 . _:b558137563 . _:b558136564 "5"^^ . _:b558137556 . _:b558136272 . _:b558136910 . _:b558137905 . _:b558137557 . . _:b558137558 . _:b558137559 . _:b558137592 . _:b558136567 "5"^^ . . _:b558137552 . . _:b558137553 . _:b558136905 . _:b558137554 . . _:b558137139 . _:b558137555 . _:b558136566 "5"^^ . _:b558137548 . _:b558136904 . _:b558137549 . _:b558137550 . _:b558137551 . _:b558136561 "5"^^ . _:b558137544 . _:b558136462 . _:b558137545 . _:b558136907 . _:b558137546 . _:b558137547 . _:b558136560 "5"^^ . _:b558137540 . _:b558136906 . _:b558137029 . _:b558137541 . _:b558137542 . _:b558137543 . _:b558136563 "5"^^ . _:b558137536 . . _:b558136917 . _:b558137537 . _:b558137538 . _:b558137539 . . _:b558136562 "5"^^ . _:b558137596 . _:b558136916 . _:b558137597 . _:b558137598 . _:b558137620 . _:b558136377 . _:b558137599 . _:b558136573 "5"^^ . _:b558137592 . . _:b558136919 . _:b558137593 . _:b558137594 . _:b558137244 . _:b558137595 . _:b558136572 "5"^^ . _:b558137588 . . _:b558136918 . _:b558137572 . _:b558137589 . _:b558137590 . _:b558137591 . _:b558136575 "5"^^ . _:b558137584 . . . _:b558137585 . _:b558136913 . _:b558137586 . _:b558136640 . _:b558137587 . _:b558136574 "5"^^ . _:b558137580 . _:b558136912 . _:b558137660 . _:b558137581 . _:b558137582 . _:b558137583 . _:b558136569 "5"^^ . _:b558137576 . _:b558136319 . _:b558136917 . _:b558136915 . _:b558137577 . . _:b558137578 . . _:b558137579 . _:b558136568 "5"^^ . _:b558137572 . _:b558136914 . _:b558137573 . _:b558137574 . _:b558137575 . _:b558136571 "5"^^ . _:b558137568 . _:b558136925 . _:b558137569 . _:b558137570 . _:b558137571 . _:b558137561 . . _:b558136570 "5"^^ . _:b558137500 . _:b558136924 . _:b558137501 . _:b558137502 . _:b558137503 . _:b558136581 "5"^^ . _:b558137496 . _:b558136927 . _:b558137497 . _:b558137498 . . _:b558137499 . _:b558136580 "5"^^ . _:b558137492 . _:b558136926 . _:b558137493 . _:b558137494 . . . _:b558137495 . _:b558136583 "5"^^ . _:b558137488 . _:b558136921 . _:b558137489 . _:b558137490 . _:b558137247 . _:b558137491 . . _:b558136582 "5"^^ . _:b558137484 . _:b558136920 . _:b558137485 . _:b558136791 . _:b558137486 . . _:b558137487 . _:b558136577 "5"^^ . _:b558137480 . _:b558136923 . _:b558137481 . _:b558137482 . _:b558137483 . _:b558136576 "5"^^ . _:b558137476 . _:b558136922 . _:b558137477 . _:b558137478 . _:b558137479 . _:b558136579 "5"^^ . _:b558137472 . _:b558137473 . _:b558136933 . . _:b558137474 . _:b558136953 . . _:b558137475 . _:b558136578 "5"^^ . _:b558137532 . . . _:b558137533 . _:b558136932 . _:b558136489 . _:b558137534 . _:b558137535 . _:b558136589 "5"^^ . _:b558137528 . . _:b558137529 . _:b558136935 . _:b558137530 . _:b558137531 . _:b558136588 "5"^^ . _:b558137524 . _:b558137525 . _:b558136934 . _:b558137526 . _:b558137527 . _:b558136591 "5"^^ . _:b558137520 . _:b558136929 . _:b558137521 . _:b558137522 . _:b558137566 . _:b558137523 . _:b558136590 "5"^^ . _:b558137516 . _:b558136928 . _:b558137517 . _:b558137518 . _:b558138165 . _:b558136258 . _:b558137519 . _:b558136585 "5"^^ . _:b558137512 . . _:b558137513 . _:b558136931 . . _:b558137514 . . _:b558137515 . _:b558136584 "5"^^ . . _:b558137508 . . _:b558137509 . _:b558136930 . . _:b558137510 . _:b558137511 . _:b558136587 "5"^^ . _:b558137504 . _:b558137505 . _:b558137758 . _:b558136941 . _:b558137506 . _:b558137507 . _:b558136586 "5"^^ . _:b558137436 . _:b558137437 . _:b558136940 . _:b558137438 . . _:b558137439 . _:b558136597 "5"^^ . _:b558137432 . . _:b558136943 . _:b558137433 . _:b558137434 . _:b558137435 . _:b558136596 "5"^^ . _:b558137428 . _:b558137429 . _:b558136942 . _:b558137430 . . _:b558137431 . _:b558136599 "5"^^ . _:b558137424 . _:b558137425 . _:b558136937 . _:b558137426 . _:b558137427 . _:b558136598 "5"^^ . _:b558137420 . _:b558137421 . _:b558136936 . _:b558137422 . _:b558137423 . _:b558136593 "5"^^ . _:b558137276 . _:b558137416 . _:b558137417 . _:b558136939 . _:b558137418 . _:b558137419 . _:b558136592 "5"^^ . . _:b558137412 . _:b558137413 . _:b558137109 . _:b558136938 . _:b558137414 . . _:b558137415 . _:b558136595 "5"^^ . _:b558137408 . _:b558137409 . _:b558136949 . _:b558137410 . . _:b33179865 "To validate our method we used a breast cancer cell line (SK-BR-3) that was previously shown to be genetically monoclonal11,>>17<<. We evaluated the genetic homogeneity of this cell line using spectral karyotyping and found that large chromosome rearrangements were highly stable in 85.80% of the single cells (Supplementary Table 1)." . _:b558137411 . _:b558136594 "5"^^ . _:b558138046 . _:b558137468 . _:b558137469 . _:b558136948 . _:b558137470 . _:b558136961 . _:b558137471 . _:b558136605 "5"^^ . _:b558137464 . . _:b558137046 . _:b558136951 . _:b558137465 . _:b558137466 . _:b558137467 . _:b558136604 "5"^^ . _:b558137558 . _:b558137460 . _:b558137461 . _:b558136950 . _:b558137462 . _:b558137402 . _:b558137463 . _:b558136607 "5"^^ . _:b558137456 . _:b558137457 . _:b558136945 . _:b558137458 . . _:b558137459 . _:b558136606 "5"^^ . _:b558137452 . . _:b558136944 . _:b558137453 . _:b558137454 . . _:b558137455 . _:b558136601 "5"^^ . . _:b558137448 . _:b558137449 . _:b558136947 . _:b558136609 . _:b558137450 . _:b558137451 . _:b558136600 "5"^^ . _:b558137444 . . _:b558137445 . _:b558136946 . . _:b558137446 . _:b558137447 . . _:b558136603 "5"^^ . _:b558137440 . . . _:b558136957 . _:b558137441 . _:b558137442 . . _:b558137443 . _:b558136922 . _:b558136602 "5"^^ . _:b558137372 . . . _:b558137373 . _:b558137047 . _:b558136956 . _:b558136593 . _:b558137374 . _:b558137375 . _:b558136613 "5"^^ . _:b558137368 . _:b558137369 . _:b558136959 . _:b558136871 . _:b558137370 . _:b558137371 . _:b558136612 "5"^^ . _:b558137364 . _:b558137365 . _:b33179849 "A punctuated model is consistent with the mechanisms that underlie CNAs, including chromosome missegregation>>32<<, cytokinesis defects and breakage-fusion-bridge33, which can generate complex rearrangements in just a few cell divisions." . _:b558136958 . . _:b558137366 . . _:b558137367 . . _:b558136615 "5"^^ . _:b558137360 . . _:b558136953 . _:b558137361 . _:b558137362 . _:b558137152 . _:b558137363 . _:b558137413 . _:b558136614 "5"^^ . _:b558137356 . _:b558137357 . _:b558136952 . . _:b558137358 . _:b558137359 . _:b558136609 "5"^^ . _:b558137352 . _:b558137353 . _:b558136955 . _:b558137354 . _:b558137355 . _:b558136608 "5"^^ . _:b558137348 . . _:b558136954 . _:b558137349 . _:b558136865 . _:b558137350 . _:b558137351 . _:b558137449 . _:b558136611 "5"^^ . _:b558137344 . _:b558137345 . _:b33179860 . _:b558136965 . _:b558137346 . _:b558137347 . . _:b558136610 "5"^^ . _:b558137404 . . _:b558136964 . _:b558137405 . . _:b558137406 . _:b558137407 . . _:b558136621 "5"^^ . _:b558137187 . _:b558137030 . _:b558137400 . . . _:b558136967 . _:b558137401 . . _:b558137732 . _:b558137402 . _:b558137403 . _:b558136620 "5"^^ . _:b558137396 . _:b558137397 . _:b558136966 . _:b558137398 . _:b558137399 . _:b558136623 "5"^^ . _:b558137177 . _:b558137392 . _:b558137393 . _:b558136961 . . _:b558137394 . . _:b558137395 . _:b558136622 "5"^^ . _:b558137388 . _:b558137389 . _:b558137634 . _:b558136960 . _:b558137390 . . _:b558137391 . _:b558136617 "5"^^ . _:b558137384 . _:b558137385 . _:b558136963 . _:b558137386 . _:b558137387 . _:b558136616 "5"^^ . _:b558137380 . _:b558136699 . _:b558137381 . _:b558138136 . _:b558136962 . _:b558137382 . _:b558137877 . _:b558137383 . _:b558136619 "5"^^ . _:b558137376 . _:b558137377 . _:b558136973 . _:b558137378 . _:b558137379 . . _:b558136618 "5"^^ . _:b558137820 . _:b558137821 . _:b558136972 . _:b558137822 . _:b558136336 . _:b558137823 . _:b558136629 "5"^^ . _:b558137816 . _:b558137817 . _:b558136975 . _:b558137818 . . _:b558137819 . _:b558136628 "5"^^ . _:b558137812 . _:b558136446 . _:b558137813 . _:b558136974 . _:b558137814 . _:b558137815 . _:b558136631 "5"^^ . _:b558137808 . . _:b558136969 . _:b558137809 . _:b558137810 . _:b558137811 . _:b558136630 "5"^^ . _:b558137804 . . . _:b558137357 . _:b558136968 . _:b558137805 . . _:b558136353 . _:b558137280 . _:b558137806 . . _:b558137807 . _:b558136625 "5"^^ . _:b558137800 . . _:b558136622 . _:b558136971 . _:b558137801 . _:b558137802 . _:b558136283 . _:b558137803 . _:b558136624 "5"^^ . _:b558137796 . _:b558137797 . _:b558136970 . . _:b558137798 . . _:b558137799 . . _:b558137792 . _:b558136627 "5"^^ . . _:b558136981 . _:b558137793 . _:b558136587 . _:b558137794 . _:b558137795 . _:b558136626 "5"^^ . _:b558137852 . _:b558137853 . _:b558136980 . _:b558137854 . _:b558137855 . _:b558136637 "5"^^ . _:b558137848 . _:b558137849 . _:b558136983 . _:b558137850 . . _:b558137851 . _:b558136636 "5"^^ . _:b558138122 . _:b558137844 . _:b558137845 . _:b558136982 . _:b558137846 . _:b558137847 . _:b558136639 "5"^^ . _:b558137493 . _:b558137840 . _:b558136415 . _:b558137841 . _:b558136977 . _:b558137842 . . _:b558137843 . _:b558136638 "5"^^ . _:b558137836 . _:b558136471 . _:b558136976 . _:b558137837 . _:b558136835 . _:b558137838 . _:b558137208 . _:b558137839 . _:b558136633 "5"^^ . _:b558137578 . _:b558137832 . _:b558136761 . _:b558137833 . _:b558136979 . _:b558137834 . _:b558137835 . _:b558136632 "5"^^ . _:b558137828 . _:b558137829 . _:b558136978 . _:b558137830 . _:b558137831 . . _:b558137824 . _:b558136635 "5"^^ . _:b558137825 . _:b558136989 . _:b558137826 . _:b558137827 . _:b558136634 "5"^^ . _:b558137193 . _:b558137756 . _:b558137757 . _:b558136988 . . _:b558137758 . _:b558136645 "4"^^ . _:b558137759 . _:b558137752 . _:b558137753 . _:b558136991 . _:b558137754 . _:b558136644 "4"^^ . _:b33179885 . _:b558137455 . _:b558137316 . _:b558137755 . . _:b558137748 . _:b558137749 . _:b558136990 . _:b558137750 . _:b558136647 "4"^^ . . _:b558137751 . _:b558136832 . _:b558137744 . _:b558137745 . _:b558136985 . _:b558137746 . _:b558137067 . _:b558136981 . _:b558136646 "4"^^ . _:b558137747 . _:b558136844 . _:b558137740 . _:b558137741 . _:b558136984 . _:b558137742 . . _:b558137743 . _:b558136641 "5"^^ . _:b558137736 . _:b558137737 . _:b558136987 . _:b558137738 . _:b558137739 . _:b558136640 "5"^^ . _:b558137732 . _:b558136305 . _:b558137733 . _:b558136986 . . _:b558137734 . _:b558136643 "4"^^ . _:b558137735 . _:b558137728 . _:b558137729 . _:b558136997 . . _:b558137730 . _:b558136642 "4"^^ . _:b558137731 . . . _:b558137788 . _:b558137789 . _:b558136996 . _:b558137790 . . _:b558137791 . _:b558136653 "4"^^ . _:b558137784 . _:b558137785 . _:b558136999 . _:b558137786 . _:b558136652 "4"^^ . _:b558137787 . _:b558137780 . _:b558137781 . _:b558136998 . _:b558137782 . _:b558136655 "4"^^ . _:b558137783 . _:b558137776 . _:b558137777 . _:b558136993 . _:b558137778 . _:b558136654 "4"^^ . _:b558136936 . _:b558137779 . . _:b558137772 . _:b558137773 . _:b558136992 . . _:b558137774 . _:b558136649 "4"^^ . _:b558137775 . _:b558137768 . _:b558137737 . _:b558136662 . . _:b558138010 . _:b558136995 . _:b558137769 . _:b558137770 . _:b558136648 "4"^^ . _:b558137771 . _:b558137764 . _:b558137765 . _:b558138085 . _:b558136994 . _:b558137766 . _:b558136651 "4"^^ . _:b558137767 . _:b558137760 . _:b558136887 . _:b558137005 . _:b558137761 . _:b558137762 . _:b558136650 "4"^^ . _:b558137763 . . _:b558137692 . . _:b558137693 . _:b558137004 . . _:b558137694 . _:b558136661 "4"^^ . _:b558137728 . _:b558137497 . _:b558137695 . _:b558137688 . _:b558137689 . _:b33179852 "These rare mutations may play an important role in diversifying the phenotypes of cancer cells, allowing them to surive selective pressures in the tumor microenvironment, including the immune system, hypoxia and chemotherapy>>35<<,36." . _:b558137007 . . _:b558137690 . _:b558136254 . _:b558136660 "4"^^ . _:b558137691 . _:b558137684 . _:b558137685 . _:b558137006 . _:b558137686 . _:b558136663 "4"^^ . _:b558137687 . _:b558136410 . _:b558137680 . . _:b558137001 . _:b558137681 . _:b558137682 . _:b558136662 "4"^^ . _:b558137683 . . _:b558137676 . _:b558137677 . _:b558137000 . _:b558137678 . _:b558136657 "4"^^ . _:b558137679 . _:b558137672 . _:b558137673 . _:b558137003 . _:b558137674 . _:b558136656 "4"^^ . _:b558137675 . . _:b558137668 . _:b558137979 . _:b558137669 . _:b558137002 . _:b558137670 . _:b558136659 "4"^^ . _:b558137671 . _:b558137664 . _:b558137665 . _:b558137013 . _:b558137666 . _:b558136658 "4"^^ . _:b558137667 . _:b558137724 . _:b558137725 . _:b558137012 . _:b558137726 . _:b558136669 "4"^^ . _:b558137727 . _:b558137720 . _:b558137721 . _:b558137015 . _:b558137722 . _:b558136668 "4"^^ . _:b558137723 . _:b558137716 . _:b558137717 . _:b558137014 . _:b558137718 . _:b558137680 . _:b558136671 "4"^^ . _:b558137719 . _:b558137712 . _:b558136713 . _:b558137713 . _:b558137009 . _:b558136372 . . _:b558137714 . _:b558136670 "4"^^ . _:b558137715 . _:b558137708 . . _:b558137640 . _:b558137008 . _:b558137709 . _:b558137710 . _:b558136665 "4"^^ . _:b558137711 . _:b558137704 . _:b558137705 . _:b558137011 . _:b558137706 . _:b558138121 . _:b558137266 . _:b558136664 "4"^^ . _:b558137707 . _:b558137700 . _:b558137701 . _:b558137010 . _:b558137702 . _:b558136667 "4"^^ . _:b558137703 . _:b558137696 . _:b558137697 . _:b558137021 . _:b558137698 . _:b558136666 "4"^^ . _:b558137699 . _:b558137628 . . _:b558137020 . _:b558137629 . . _:b558137630 . _:b558136677 "4"^^ . _:b558137631 . _:b558137624 . _:b558137625 . _:b558137023 . _:b558137626 . _:b558136676 "4"^^ . _:b558137671 . _:b558137627 . . _:b558137620 . _:b558136427 . _:b558137621 . _:b558137022 . _:b558136563 . _:b558137622 . _:b558136679 "4"^^ . _:b558137623 . _:b558136252 . _:b558137616 . _:b558137617 . _:b558137017 . _:b558137618 . _:b558136678 "4"^^ . _:b558137619 . _:b558137612 . _:b558137613 . _:b558137016 . _:b558137614 . _:b558136673 "4"^^ . _:b558137209 . _:b558137615 . _:b558137608 . _:b558137720 . _:b558137609 . _:b558137019 . . _:b558137610 . _:b558136672 "4"^^ . _:b558137611 . _:b558136725 . _:b558137604 . _:b558137605 . _:b558137043 . _:b558137018 . _:b558137606 . _:b558136675 "4"^^ . _:b558137607 . . _:b558137600 . _:b558137601 . _:b558137029 . . _:b558137602 . _:b558136674 "4"^^ . _:b558137603 . . _:b558137660 . _:b558137661 . _:b558137028 . . _:b558137662 . _:b558136685 "4"^^ . _:b558137663 . _:b558137656 . _:b558137657 . _:b558137031 . _:b558137658 . _:b558136684 "4"^^ . _:b558137765 . _:b558137659 . _:b558137652 . _:b558137653 . _:b558137030 . _:b558137654 . _:b558136687 "4"^^ . _:b558137655 . . _:b558137648 . _:b558137649 . _:b558137112 . _:b558137025 . _:b558137650 . _:b558136686 "4"^^ . _:b558137651 . _:b558137644 . _:b558137645 . _:b558137024 . _:b558137646 . . _:b558136681 "4"^^ . _:b558137647 . _:b558137640 . _:b558137641 . _:b558137027 . . _:b558137731 . _:b558137642 . _:b558136680 "4"^^ . _:b558137643 . . . _:b558137636 . _:b558137637 . _:b558137375 . _:b558137026 . _:b558137638 . _:b558136683 "4"^^ . _:b558137639 . _:b558137632 . _:b558137633 . _:b558137037 . _:b558137634 . _:b558136682 "4"^^ . _:b558137635 . _:b558138076 . _:b33179863 . _:b558136849 . _:b558137036 . _:b558138077 . . _:b558138078 . _:b558136693 "4"^^ . _:b558138079 . . _:b558138072 . _:b558138073 . _:b558137039 . _:b558138074 . _:b558136692 "4"^^ . _:b558138075 . _:b558136598 . _:b558138068 . _:b558138069 . _:b558137038 . _:b558138070 . _:b558136695 "4"^^ . _:b558138071 . _:b558138064 . _:b558138065 . _:b558137248 . _:b558137033 . _:b558138066 . _:b558136694 "4"^^ . _:b558138067 . . _:b558138060 . _:b558138061 . _:b558137032 . . _:b558138062 . _:b558136689 "4"^^ . _:b558138063 . _:b558136907 . _:b558138056 . _:b558138057 . _:b558137035 . _:b558138058 . _:b558136688 "4"^^ . _:b558138059 . . _:b558138052 . _:b558138053 . _:b558137034 . _:b558138054 . _:b558136691 "4"^^ . _:b558138055 . . _:b558138048 . _:b558138049 . _:b558137045 . _:b558138050 . _:b558136690 "4"^^ . _:b558138051 . _:b558138108 . _:b558137795 . _:b558138109 . _:b558137044 . _:b558138110 . _:b558138060 . _:b558136701 "4"^^ . _:b558138111 . _:b558138104 . . _:b558137047 . _:b558138105 . _:b558138106 . _:b558136700 "4"^^ . _:b558138107 . . _:b558138100 . _:b558138101 . _:b558137046 . _:b558138102 . _:b558136703 "4"^^ . _:b558138103 . _:b558138096 . . _:b558137041 . _:b558138097 . _:b558138098 . _:b558136702 "4"^^ . _:b558138099 . _:b558138092 . _:b558136698 . _:b558137238 . _:b558137040 . _:b558138093 . _:b558138094 . _:b558136840 . _:b558138095 . _:b558136697 "4"^^ . _:b558138088 . _:b558137503 . _:b558138089 . _:b558137173 . _:b558137043 . _:b558136516 . _:b558138090 . _:b558136696 "4"^^ . _:b558138091 . _:b558138084 . _:b558138085 . _:b558137042 . _:b558138086 . _:b558136699 "4"^^ . _:b558138087 . _:b558138080 . . _:b558137377 . _:b558137053 . _:b558138081 . _:b558138082 . _:b558136698 "4"^^ . _:b558138083 . . _:b558138012 . _:b558138013 . _:b558137052 . _:b558136422 . _:b558138014 . _:b558136709 "4"^^ . _:b558138015 . _:b558138008 . _:b558138009 . _:b558137055 . _:b558138010 . . _:b558138011 . _:b558136708 "4"^^ . _:b558138004 . . _:b558137742 . _:b558137054 . _:b558138005 . _:b558138006 . _:b558136711 "4"^^ . _:b558138007 . _:b558138000 . _:b558137781 . _:b558138001 . _:b558137049 . _:b558138002 . _:b558137553 . _:b558136710 "4"^^ . _:b558138003 . . _:b558137996 . _:b558137997 . _:b558138028 . _:b558137048 . . _:b558137998 . _:b558136705 "4"^^ . _:b558137999 . . _:b558137992 . _:b558136378 . _:b558137747 . _:b558137051 . _:b558137993 . _:b558136700 . _:b558137994 . _:b558137095 . _:b558136704 "4"^^ . _:b558137995 . _:b558137988 . _:b558137989 . _:b558137752 . _:b558137050 . _:b558136494 . _:b558137990 . . _:b558136707 "4"^^ . _:b558137887 . _:b558137991 . _:b558136612 . . _:b558137984 . . _:b558137061 . _:b558137985 . _:b558137986 . _:b558136706 "4"^^ . _:b558137987 . . _:b558138044 . _:b558138045 . _:b558137060 . _:b558138046 . _:b558137023 . _:b558136717 "4"^^ . _:b558138047 . _:b558138040 . _:b558138041 . _:b558137063 . _:b558138042 . _:b33179870 "Our analysis suggests that Nuc-Seq generates low allelic dropout rates (9.73% \u00B1 2.19%) compared to previous studies (7\u201346%)>>14<<. We also achieved low false positive error rates for point mutations (FPR = 1.24e-6), equivalent to 1\u20132 errors per million bases, which represents a major technical improvement over previous methods (FPR= 2.52e-5 and 4e-5)14,19." . _:b558136716 "4"^^ . _:b558138043 . . _:b558138036 . . _:b558137062 . _:b558138037 . _:b558138038 . _:b558136719 "4"^^ . _:b558138039 . . . _:b558138032 . . _:b558138033 . _:b558137057 . . _:b558138034 . _:b558136718 "4"^^ . _:b558138035 . _:b558138028 . _:b558138029 . _:b558137056 . _:b558138030 . _:b558136713 "4"^^ . _:b558138031 . _:b558138024 . _:b558138025 . _:b558137200 . _:b558137059 . . _:b558138026 . _:b558136712 "4"^^ . _:b558138027 . _:b558138020 . . _:b558138021 . _:b558137058 . _:b558138022 . _:b558136715 "4"^^ . _:b558138023 . . _:b558138016 . _:b558138017 . _:b558137069 . _:b558136389 . . _:b558138018 . _:b558136714 "4"^^ . _:b558138019 . _:b558137948 . _:b558137786 . . _:b558137068 . _:b558137949 . _:b558137950 . _:b558136725 "4"^^ . _:b558137951 . _:b558137944 . _:b558137945 . _:b558137223 . _:b558137071 . . _:b558137946 . _:b558136724 "4"^^ . _:b558137428 . _:b558137947 . _:b558137940 . _:b558137941 . _:b558137716 . _:b558137070 . _:b558137942 . _:b558137407 . _:b558136727 "4"^^ . _:b558137943 . _:b558137936 . _:b558137937 . _:b558137065 . _:b558137938 . _:b558136726 "4"^^ . _:b558137939 . _:b558137932 . _:b558136310 . _:b558137064 . _:b558137933 . _:b558137934 . _:b558136721 "4"^^ . _:b558138088 . _:b558137935 . _:b558136805 . _:b558137928 . _:b558137929 . _:b558137857 . _:b558137067 . _:b558137930 . _:b558136720 "4"^^ . _:b558137931 . _:b558137924 . _:b558137925 . _:b558137066 . . . _:b558137926 . _:b558136723 "4"^^ . _:b558137927 . _:b558137920 . _:b558137921 . _:b558137733 . _:b558137077 . _:b558137922 . _:b558136722 "4"^^ . _:b558137923 . _:b558137980 . _:b558137981 . _:b558137076 . _:b558137982 . _:b558136733 "4"^^ . _:b558137983 . _:b558136614 . . _:b558137976 . _:b558137977 . _:b558137079 . . _:b558137978 . _:b558136732 "4"^^ . _:b558137979 . _:b558137972 . _:b558137973 . _:b558137078 . . _:b558137974 . _:b558136735 "4"^^ . _:b558137975 . _:b558137968 . _:b558137969 . _:b558137073 . . _:b558137970 . _:b558136734 "4"^^ . _:b558137971 . . _:b558137964 . _:b558137965 . _:b558137072 . . _:b558137966 . _:b558136729 "4"^^ . _:b558137967 . . _:b558137960 . _:b558137961 . _:b558137075 . _:b558137962 . _:b558136728 "4"^^ . _:b558137963 . _:b558137956 . . _:b558137074 . _:b558137957 . _:b558137958 . _:b558136731 "4"^^ . _:b558137959 . _:b558137952 . . _:b558137085 . _:b558137953 . . _:b558137883 . _:b558137954 . _:b558136730 "4"^^ . _:b558137955 . _:b558137884 . _:b558137885 . _:b558137084 . _:b558137886 . _:b558136741 "4"^^ . _:b558138126 . _:b558137887 . _:b558136616 . _:b558137880 . _:b558137881 . _:b558137087 . _:b558137882 . _:b558136740 "4"^^ . _:b558137883 . . . _:b558137876 . . _:b558137877 . _:b558137086 . _:b558137878 . _:b558136743 "4"^^ . _:b558137879 . _:b558137872 . . _:b558137873 . _:b558137081 . _:b558137874 . . _:b558137875 . _:b558136742 "4"^^ . . _:b558137868 . . _:b558137080 . _:b558137869 . _:b558137870 . _:b558137434 . _:b558136737 "4"^^ . _:b558137871 . _:b558137864 . . _:b558137083 . _:b558137865 . _:b558137866 . _:b558136736 "4"^^ . _:b558137867 . _:b558137860 . _:b558137861 . _:b558137082 . . _:b558137862 . _:b558136739 "4"^^ . _:b558137863 . _:b558137856 . _:b558136581 . _:b558137857 . _:b558137858 . _:b558136738 "4"^^ . _:b558137859 . _:b558137916 . _:b558136580 . _:b558137917 . _:b558137918 . _:b558136749 "4"^^ . _:b558137919 . _:b558137912 . _:b558136583 . _:b558137456 . _:b558137913 . _:b558137914 . _:b558136748 "4"^^ . _:b558136901 . _:b558137915 . _:b558137908 . _:b558138163 . _:b558136582 . _:b558137909 . _:b558137910 . _:b558136751 "4"^^ . _:b558137911 . . _:b558137904 . . _:b558137905 . _:b558136577 . _:b558137906 . _:b558136750 "4"^^ . _:b558137907 . _:b558137900 . _:b558136576 . _:b558137901 . _:b558137902 . _:b558137176 . . _:b558137903 . _:b558136745 "4"^^ . _:b558137896 . _:b558136579 . _:b558137897 . _:b558137898 . _:b558136744 "4"^^ . _:b558137899 . _:b558137892 . _:b558136578 . _:b558138156 . _:b558137893 . . _:b558137894 . _:b558136747 "4"^^ . _:b558137895 . _:b558137888 . _:b558136589 . _:b558137630 . _:b558137889 . _:b558137890 . _:b558136746 "4"^^ . _:b558137891 . _:b558136588 . _:b558136757 "4"^^ . . . _:b558136591 . . . _:b558136756 "4"^^ . _:b558136285 . _:b558136590 . _:b558137894 . _:b558136759 "4"^^ . . _:b558136585 . _:b558136758 "4"^^ . _:b558137132 . _:b558137689 . . _:b558137219 . _:b558136584 . _:b558136736 . _:b558136624 . _:b558136753 "4"^^ . _:b558136504 . _:b558137041 . . . _:b558136587 . . _:b558136752 "4"^^ . _:b558136586 . _:b558136306 . _:b558137860 . . _:b558136755 "4"^^ . _:b558137409 . _:b558136597 . _:b558136754 "4"^^ . _:b558136596 . _:b558136765 "4"^^ . _:b558136599 . _:b558136764 "4"^^ . _:b558137098 . _:b558136598 . _:b558136767 "4"^^ . _:b558136593 . _:b558136766 "4"^^ . _:b558137850 . _:b558136592 . _:b33179879 . _:b558136761 "4"^^ . _:b558137754 . _:b558136595 . _:b558137491 . _:b558136760 "4"^^ . _:b558137515 . _:b558136594 . _:b558136763 "4"^^ . _:b558136605 . _:b558137279 . _:b558136762 "4"^^ . _:b558136604 . _:b558137198 . _:b558136773 "4"^^ . . _:b558136607 . _:b558137543 . _:b558136772 "4"^^ . _:b558136606 . _:b558136775 "4"^^ . _:b558137212 . _:b558136601 . _:b558136774 "4"^^ . _:b558136600 . _:b558137643 . _:b558136769 "4"^^ . _:b558136603 . . _:b558136768 "4"^^ . _:b558136602 . . _:b558136771 "4"^^ . . _:b558136613 . _:b558136325 . _:b558136770 "4"^^ . . _:b558136612 . _:b558136781 "4"^^ . _:b558136615 . _:b558137514 . _:b558136780 "4"^^ . _:b558136614 . _:b558137144 . _:b558137924 . _:b558136595 . _:b558136783 "4"^^ . . _:b558136609 . _:b558136782 "4"^^ . _:b558136608 . . _:b558136777 "4"^^ . _:b558136438 . _:b558136611 . _:b558137127 . _:b558136776 "4"^^ . . _:b558136610 . _:b558137726 . _:b558136779 "4"^^ . _:b558136621 . _:b558136778 "4"^^ . _:b558136620 . _:b558136789 "4"^^ . _:b558136623 . . _:b558136788 "4"^^ . _:b558136479 . _:b558137751 . . _:b558136622 . . _:b558136791 "4"^^ . . . _:b558136617 . _:b558136790 "4"^^ . . _:b558136616 . . _:b558136785 "4"^^ . _:b558137271 . _:b558136619 . _:b558136784 "4"^^ . _:b558136687 . _:b558136618 . _:b33179873 "population and single nuclei sequencing of an er tumor" . _:b558136787 "4"^^ . _:b558137644 . _:b558137180 . _:b558136629 . _:b558136786 "4"^^ . _:b558136628 . _:b558136797 "4"^^ . _:b558137645 . . _:b558136669 . _:b558136631 . . _:b558136796 "4"^^ . _:b558136630 . _:b558136799 "3"^^ . . _:b558136625 . . _:b558136798 "4"^^ . _:b558136624 . _:b558136793 "4"^^ . _:b558136627 . _:b558136792 "4"^^ . _:b558136626 . _:b558138037 . _:b558136795 "4"^^ . _:b558136688 . _:b558136637 . _:b558136794 "4"^^ . . _:b558138140 . . _:b558138141 . _:b558136636 . . _:b558138142 . . _:b558136805 "3"^^ . _:b558138143 . . . _:b558138136 . . _:b558138137 . _:b558136639 . _:b558138138 . _:b558136804 "3"^^ . _:b558138139 . _:b558138132 . _:b558138133 . _:b558136638 . _:b558138134 . _:b558136807 "3"^^ . _:b558138135 . _:b558138128 . _:b558138129 . _:b558136633 . . _:b558138130 . _:b558136806 "3"^^ . _:b558138131 . _:b558138124 . _:b558137544 . _:b558138125 . _:b558136632 . _:b558138126 . _:b558137794 . _:b558136801 "3"^^ . _:b558138127 . _:b558138120 . _:b558138121 . _:b558136635 . _:b558136530 . _:b558138122 . _:b558137790 . _:b558136800 "3"^^ . _:b558138123 . . _:b558138116 . _:b558138117 . _:b558136634 . . _:b558138118 . _:b558136803 "3"^^ . _:b558138119 . . _:b558138112 . _:b558138113 . _:b558136645 . _:b558138114 . _:b558136802 "3"^^ . _:b558138115 . _:b558136644 . _:b558136813 "3"^^ . _:b558136647 . _:b558136812 "3"^^ . . _:b558138164 . _:b558138165 . _:b558136646 . _:b558138166 . _:b558136815 "3"^^ . . . _:b558138167 . _:b558138160 . _:b558138161 . _:b558136641 . _:b558138162 . _:b558136814 "3"^^ . _:b558138163 . _:b558138156 . _:b558138157 . _:b558136640 . _:b558138158 . _:b558136809 "3"^^ . _:b558138159 . _:b558138152 . _:b558138153 . _:b558136643 . . _:b558138154 . _:b558136808 "3"^^ . _:b558138155 . . _:b558136928 . _:b558138148 . . _:b558138149 . _:b558136642 . . _:b558138150 . _:b558136811 "3"^^ . _:b558138151 . . _:b558138144 . . _:b558138145 . _:b558137710 . _:b558136653 . _:b558138146 . _:b558136810 "3"^^ . _:b558138147 . . _:b558136401 . _:b558136652 . _:b558136543 . _:b558136821 "3"^^ . _:b558136655 . _:b558136820 "3"^^ . . _:b558136654 . _:b558136823 "3"^^ . . _:b558136649 . _:b558137246 . _:b558136822 "3"^^ . _:b558136648 . _:b558138076 . . _:b558136548 . _:b558136817 "3"^^ . . . _:b558136651 . _:b558136816 "3"^^ . _:b558136650 . _:b558136819 "3"^^ . _:b558136667 . . _:b558136661 . _:b558136818 "3"^^ . _:b558137890 . . . _:b558136660 . . _:b558136829 "3"^^ . _:b558136300 . _:b558136831 . _:b558136663 . _:b558136828 "3"^^ . _:b558136662 . . _:b558136831 "3"^^ . _:b558136843 . . _:b558136657 . _:b558136830 "3"^^ . _:b558137275 . _:b558136656 . _:b558136825 "3"^^ . _:b558136659 . _:b558136824 "3"^^ . . _:b558136658 . _:b558136827 "3"^^ . . _:b558136669 . . _:b558136826 "3"^^ . _:b558136668 . _:b558136685 . . _:b558137258 . _:b558136671 . _:b558137107 . . _:b558136670 . . . _:b558137411 . _:b558136665 . . _:b558137192 . _:b558136664 . . _:b558136417 . _:b558136559 . _:b558136667 . . . _:b558137340 . _:b558138062 . _:b558136666 . _:b558136677 . _:b558137347 . _:b558136676 . _:b558137345 . _:b558136679 . . _:b558136678 . _:b33179878 . _:b558137798 . _:b558136673 . . _:b558136672 . _:b558137911 . . . _:b558138117 . _:b558136675 . _:b558136674 . _:b33179874 . _:b558138116 . _:b558137638 . _:b558136685 . _:b558138119 . . . _:b558136665 . _:b558136684 . _:b558138118 . _:b558137504 . . _:b558138113 . _:b558136687 . . _:b558136686 . _:b558138112 . . _:b558136681 . _:b558138115 . . . _:b558136680 . _:b558138114 . . _:b558136683 . _:b558138125 . . . _:b558136682 . _:b558138124 . . . . . _:b558136693 . _:b558138127 . _:b558137750 . _:b558137682 . _:b558136692 . _:b558138126 . . _:b558136695 . _:b558138121 . _:b558136694 . _:b558138120 . . _:b558137078 . _:b558138084 . _:b558136689 . _:b558138123 . _:b558137581 . _:b558136688 . _:b558138122 . _:b558136691 . _:b558138133 . _:b558137091 . _:b558136690 . _:b558138132 . . _:b558137324 . _:b558136701 . _:b558138135 . _:b558136700 . _:b558138134 . _:b558136458 . _:b558136398 . . . _:b558136703 . _:b558138129 . _:b558136690 . _:b558136405 . _:b558136702 . _:b558138128 . . _:b558136697 . _:b558138131 . _:b558136696 . _:b558138130 . _:b558136525 . . . _:b558136699 . _:b558138141 . _:b558136698 . _:b558138140 . . _:b558136709 . _:b558138143 . _:b558137423 . . _:b558136708 . _:b558138142 . _:b558137254 . . . _:b558136267 . . . _:b558136711 . _:b558138137 . _:b558136605 . . . _:b558136710 . _:b558138136 . _:b558137214 . _:b558136705 . _:b558138139 . . _:b558136920 . _:b558137239 . _:b558136704 . _:b558138138 . _:b558137817 . _:b558137216 . _:b558137055 . _:b558136768 . _:b558136707 . _:b558138149 . . _:b558136706 . _:b558138148 . _:b558136608 . _:b558136717 . _:b558138151 . _:b558136716 . _:b558138150 . _:b558137626 . . _:b558136719 . _:b558138145 . . . _:b558138144 . _:b558136718 . _:b558136713 . _:b558138147 . . . _:b558136712 . _:b558138146 . _:b558136884 . _:b558136715 . _:b558138157 . _:b558136714 . _:b558138156 . _:b558137371 . _:b558136725 . _:b558138159 . _:b558136724 . _:b558138158 . . . . _:b558136727 . _:b558138153 . . _:b558137036 . _:b558136726 . _:b558138152 . _:b558136721 . _:b558138155 . . . _:b558136720 . _:b558138154 . . _:b558137059 . _:b558136723 . _:b558138165 . _:b558136421 . _:b558136722 . _:b558138164 . _:b558136733 . _:b558138167 . _:b558136732 . _:b558138166 . _:b558136756 . . . _:b558136735 . _:b558138161 . . _:b558137874 . _:b558136734 . _:b558138160 . _:b558137526 . . _:b558136729 . _:b558138163 . _:b558136728 . _:b558138162 . . _:b558136540 . _:b558137538 . _:b558136731 . . . _:b558136730 . _:b558136491 . _:b558136741 . _:b558136740 . . _:b558136743 . _:b558136742 . _:b558137513 . _:b558136862 . _:b558136737 . _:b558136736 . . _:b558137721 . _:b558136739 . . _:b558136942 . _:b558136738 . . _:b558136749 . _:b558137521 . _:b558136948 . _:b558136748 . . _:b33179865 . _:b558136751 . . _:b558137044 . _:b558136750 . _:b558136745 . . . _:b558136744 . _:b558136747 . . _:b558137549 . _:b558136746 . _:b558137473 . _:b558136794 . _:b558136757 . . _:b558136756 . _:b558136759 . . . _:b558136758 . _:b558136753 . _:b558137049 . _:b558136752 . _:b558137847 . _:b558136755 . _:b558136790 . _:b558136754 . . . _:b558136765 . _:b558137196 . _:b558136764 . _:b558136767 . _:b558137075 . _:b558136743 . _:b558136766 . _:b558136666 . _:b558137849 . _:b558136761 . . _:b558137825 . _:b558136760 . _:b558136588 . . _:b558136763 . . _:b558138054 . _:b558136762 . . _:b558136773 . . _:b558137868 . _:b558136772 . . . _:b558136775 . _:b558138094 . . _:b558136774 . _:b558137821 . _:b558136769 . _:b558136539 . _:b558136768 . _:b558137085 . _:b558137705 . _:b558136447 . _:b558136771 . _:b558136770 . _:b558136263 . _:b558137601 . _:b558136262 . _:b558137062 . _:b558136781 . _:b558136780 . _:b558136783 . _:b558137974 . _:b558136702 . _:b558136782 . _:b558137517 . _:b558136777 . . . _:b558136420 . _:b558136776 . . . _:b558136779 . . _:b558136778 . _:b558137215 . . _:b558136789 . _:b558137230 . _:b558136788 . . . . _:b558136791 . _:b558136790 . . _:b558136785 . . _:b558136784 . _:b558136787 . _:b558138143 . _:b558136786 . _:b558136797 . . _:b558136796 . . _:b558137604 . _:b558136799 . _:b558137342 . . _:b33179845 . . _:b558136601 . _:b558136798 . _:b33179846 . _:b558136642 . _:b558136793 . _:b33179847 . . . . . _:b558136792 . _:b558136795 . _:b558137571 . _:b558136526 . _:b558136794 . . _:b558136805 . _:b558136804 . _:b33179852 . _:b558136807 . _:b33179853 . . _:b558136806 . _:b33179854 . _:b558136985 . _:b558136801 . _:b33179855 . _:b558136800 . _:b33179848 . _:b558136584 . . . _:b558136803 . _:b33179849 . _:b558136851 . . _:b558136802 . _:b33179850 . . _:b558136576 . _:b558136813 . _:b33179851 . _:b558137506 . _:b558136812 . _:b33179860 . . . . _:b558136923 . _:b558136815 . _:b33179861 . . . _:b558136814 . _:b33179862 . . _:b558136910 . _:b558136809 . _:b33179863 . _:b558137117 . . _:b558136808 . _:b33179856 . _:b558136811 . _:b33179857 . _:b558137265 . _:b33179850 . _:b558136810 . _:b33179858 . _:b558136821 . _:b33179859 . . _:b558136855 . _:b558136820 . _:b33179868 . _:b558136399 . . _:b558136823 . _:b33179869 . . _:b558137440 . _:b558136822 . _:b33179870 . _:b558137202 . . . _:b558136817 . _:b33179871 . _:b558136897 . _:b558136816 . . _:b33179864 . _:b558137319 . _:b558136819 . _:b33179865 . _:b558136818 . _:b33179866 . _:b558137611 . _:b558136829 . _:b33179867 . . _:b558136828 . _:b33179876 . . . _:b558136831 . _:b33179877 . . _:b558137227 . _:b558136830 . _:b33179878 . _:b558136825 . _:b33179879 . _:b558138059 . _:b558137170 . _:b558137584 . _:b33179854 . _:b558136824 . _:b33179872 . _:b558137228 . _:b558136827 . _:b558136331 . _:b33179873 . _:b558137400 . . _:b33179853 . _:b558136826 . _:b33179874 . . _:b558136325 . _:b33179875 . . . . _:b558136594 . _:b558137552 . . _:b558136324 . _:b33179884 . _:b558136327 . _:b33179885 . . _:b558136326 . _:b558137527 . _:b558136321 . . . _:b558136320 . _:b33179880 . _:b558136747 . _:b558136323 . . _:b33179881 . _:b558137586 . _:b558136322 . _:b33179882 . _:b558137233 . _:b558136333 . _:b558137123 . _:b33179883 . . _:b558136332 . _:b558136335 . _:b558136334 . . . _:b558136329 . _:b558136328 . _:b558136411 . . _:b558137262 . . _:b558136331 . . _:b558136330 . . . . _:b558136341 . _:b558136448 . _:b558137431 . . . . _:b558136340 . . _:b558136343 . . . _:b558136342 . . _:b558136337 . . _:b558137472 . _:b558136336 . _:b558136339 . _:b558137178 . _:b558136338 . _:b558136349 . _:b558136348 . _:b558136351 . _:b558136350 . _:b558137511 . . . _:b558136506 . _:b558136345 . . _:b558136400 . _:b558136344 . . _:b558136347 . . . _:b558136346 . _:b558136357 . _:b558137677 . _:b558136356 . _:b558136772 . . _:b558136359 . . . _:b558136358 . . . _:b558136353 . _:b558137502 . . _:b558138146 . _:b558136352 . . _:b558137823 . _:b558136355 . _:b558137812 . _:b558136354 . _:b558136365 . _:b558136327 . _:b558136364 . _:b558136367 . _:b558137382 . _:b558136366 . _:b558138109 . . . _:b558136361 . . _:b558136360 . _:b558136604 . _:b558136363 . . _:b558136883 . _:b558136990 . _:b558136299 . _:b558136362 . . _:b558137087 . . _:b558136373 . _:b558137165 . _:b558136372 . . _:b558136375 . _:b558138125 . . _:b558136374 . _:b558137469 . _:b558136369 . . _:b558136368 . _:b558136599 . _:b558136371 . _:b558138006 . . _:b558137740 . . _:b558136370 . _:b558137679 . . . . _:b558136381 . _:b558137714 . . . _:b558136380 . _:b558136753 . . _:b558136383 . . _:b558136382 . . _:b558136377 . . . . _:b558136376 . _:b558137884 . _:b558137285 . _:b558137149 . . _:b558136379 . _:b558136378 . _:b558137225 . _:b558136389 . . _:b558136826 . _:b558136388 . . . _:b558136391 . . _:b558136390 . _:b558137439 . _:b558136385 . _:b558137435 . _:b558136742 . _:b558136384 . _:b558136387 . . _:b558136386 . _:b558136397 . . _:b558136396 . . _:b558136399 . . _:b558137389 . _:b558136398 . _:b558136984 . . . _:b558136393 . _:b558137100 . _:b558136678 . _:b558136392 . _:b558137156 . _:b558136395 . _:b558137278 . . _:b558136394 . . _:b558137125 . _:b558136405 . _:b558137575 . _:b558136404 . . . _:b558136407 . _:b558136346 . _:b558136406 . . . _:b558136401 . _:b558137550 . _:b558136400 . . _:b558137736 . _:b558136403 . _:b558136402 . . _:b558136413 . _:b558137005 . _:b558136412 . . . _:b558136415 . . _:b558136414 . . _:b558136409 . _:b558137014 . _:b558136408 . _:b558136250 . _:b558137257 . _:b558136411 . _:b558136957 . _:b558137093 . _:b558136369 . _:b558136410 . _:b558136421 . . . _:b558136420 . _:b33179863 "After MDA, we incubate the amplified DNA with a Tn5 transposase, which simultaneously fragments DNA and ligates adapters for sequencing>>16<<. The libraries are then multiplexed for exome capture or used directly for next-generation sequencing." . _:b558136423 . _:b558137624 . _:b558136422 . _:b558137137 . _:b558136417 . . . _:b558137589 . _:b558136416 . _:b558136770 . _:b558137539 . _:b558136419 . _:b558137861 . _:b558136962 . _:b558136724 . . _:b558136334 . _:b558136418 . _:b558137860 . . _:b558136429 . _:b558137863 . _:b558136511 . _:b558136428 . _:b558137862 . . _:b558136431 . _:b558137857 . _:b558136821 . _:b558136430 . _:b558137856 . . _:b558137945 . _:b558136425 . _:b558137859 . . . _:b558136424 . _:b558137858 . _:b558137889 . _:b558136427 . _:b558137869 . _:b558137854 . _:b558136426 . _:b558137868 . . . _:b558136437 . _:b558137871 . _:b558136436 . _:b558137870 . . _:b558138106 . . _:b558136630 . _:b558136439 . _:b558137865 . . _:b558136797 . _:b558136796 . _:b558136438 . _:b558137864 . _:b558137702 . _:b33179879 "Many of the subclonal mutations (23.44%) were predicted to damage protein function by both POLYPHEN>>21<< and SIFT22 (Extended Data Fig." . _:b558136433 . _:b558137867 . _:b558136432 . _:b558137866 . _:b558136435 . _:b558137877 . . _:b558136434 . _:b558137876 . _:b558136647 . _:b558136841 . _:b558137900 . _:b558138130 . _:b558136288 . _:b558137879 . . . _:b558136445 . . _:b558136444 . _:b558137878 . . _:b558136778 . _:b558136447 . _:b558137873 . _:b558136446 . _:b558137872 . _:b558136441 . _:b558137875 . . _:b558136440 . _:b558137874 . . . _:b558136443 . _:b558137885 . _:b558137073 . . _:b558136442 . _:b558137884 . _:b558136637 . _:b558137352 . _:b558136453 . _:b558137887 . . _:b558136452 . _:b558137886 . . _:b558136455 . _:b558137881 . _:b558136454 . _:b558137880 . _:b558137839 . . . _:b558136449 . _:b558137883 . _:b558136448 . _:b558137932 . _:b558137882 . . _:b558136451 . _:b558137893 . . . _:b558137460 . _:b558136450 . _:b558137892 . . _:b558137045 . . _:b558136461 . _:b558137895 . _:b558136482 . . _:b558136472 . _:b558137894 . _:b558136460 . _:b558136754 . _:b558137010 . _:b558136463 . _:b558137889 . _:b558137071 . _:b558136462 . _:b558137888 . _:b558136457 . _:b558137891 . _:b558136456 . _:b558137890 . . . _:b558136555 . _:b558137901 . _:b558136459 . . _:b558137900 . _:b558136458 . _:b558136811 . _:b558136469 . _:b558137903 . _:b558136468 . _:b558137902 . . _:b558136471 . _:b558137897 . _:b558136470 . _:b558137896 . _:b558136465 . _:b558137899 . _:b558136464 . _:b558137898 . . . _:b558136467 . _:b558137909 . _:b558137140 . . _:b558136466 . _:b558137908 . . . . _:b558136402 . _:b558136459 . _:b558136477 . _:b558137911 . . . _:b558136610 . _:b558136416 . _:b558136476 . _:b558137910 . _:b558136479 . _:b558137905 . _:b558137922 . _:b558136478 . _:b558137904 . _:b558136631 . _:b558136473 . _:b558137907 . _:b558136568 . _:b558136859 . . . _:b558136472 . _:b558137906 . . _:b558137522 . . _:b558136475 . _:b558137917 . . . _:b33179857 . . _:b558136474 . _:b558137916 . _:b558137915 . . . _:b558136679 . _:b558136485 . _:b558137919 . _:b558136484 . _:b558137918 . _:b558137909 . . _:b558136487 . _:b558137913 . . _:b558136486 . _:b558137912 . _:b558136671 . _:b558136481 . _:b558137915 . _:b558136505 . . _:b558136732 . _:b558136480 . _:b558137914 . _:b558137113 . _:b558136483 . _:b558137925 . _:b558137186 . _:b558136482 . _:b558137924 . _:b558136493 . _:b558137927 . _:b558136492 . _:b558137926 . _:b558136779 . _:b558136495 . _:b558138020 . _:b558137921 . _:b558137547 . _:b558137458 . . _:b558136478 . _:b558136494 . _:b558137920 . _:b558137637 . _:b558137545 . _:b558136489 . _:b558137923 . _:b558136396 . _:b558137922 . _:b558136488 . _:b558136491 . _:b558137933 . _:b558137060 . _:b558137534 . _:b558136490 . _:b558137932 . _:b558136501 . _:b558137935 . . _:b558136850 . _:b558136500 . _:b558137934 . . _:b558138135 . _:b558136503 . _:b558137929 . _:b558136521 . _:b558136484 . . _:b558136572 . _:b558137928 . _:b558136502 . _:b558137969 . _:b558136497 . _:b558137931 . _:b558136496 . _:b558137930 . _:b558136619 . . . _:b558137826 . _:b558136620 . _:b558136499 . _:b558137941 . _:b558136892 . . _:b558136498 . _:b558137940 . _:b558136509 . _:b558137943 . . . . _:b558136508 . _:b558137942 . . . . _:b558136511 . _:b558137937 . . _:b558136510 . _:b558137936 . . . _:b558137881 . _:b558136505 . _:b558137939 . _:b33179857 . . _:b558136504 . _:b558137938 . _:b558136524 . _:b558137011 . _:b558136507 . _:b558137949 . _:b558136854 . . _:b558137007 . _:b558138150 . _:b558136506 . _:b558137948 . _:b558136517 . _:b558137951 . . _:b558136516 . _:b558137950 . _:b558137756 . _:b558136257 . _:b558136519 . _:b558137945 . _:b558136518 . _:b558137944 . _:b558136278 . . _:b558136513 . _:b33179869 . _:b558137947 . . _:b558137487 . _:b558136512 . _:b558137946 . _:b558136515 . _:b558137957 . _:b558137535 . _:b558137205 . _:b558137145 . _:b558137917 . _:b558136514 . _:b558137956 . _:b558137068 . . . _:b558136525 . _:b558137959 . _:b558137405 . . _:b558136524 . _:b558137958 . _:b558138105 . _:b558138128 . _:b558136527 . _:b33179867 . _:b558137953 . _:b558136298 . . _:b558136526 . _:b558137952 . . _:b558136521 . _:b558137955 . . _:b558136486 . _:b558136520 . _:b558137954 . _:b558136523 . _:b558137965 . . _:b558136522 . _:b33179872 . _:b558137964 . _:b558137580 . _:b558136693 . _:b558137967 . _:b558136533 . _:b558136532 . _:b558137966 . _:b558136329 . _:b558137961 . _:b558136535 . . . _:b558136534 . _:b558137960 . _:b558136529 . _:b558137963 . _:b558136528 . _:b558137962 . . _:b558136531 . _:b558137973 . _:b558136530 . _:b558137972 . _:b558136541 . _:b558137975 . . . _:b558137976 . _:b558136412 . _:b558136906 . _:b558136540 . _:b558137974 . _:b558137695 . _:b558136543 . _:b558137969 . . . _:b558136542 . _:b558137968 . _:b558136277 . _:b558136537 . _:b558137971 . . _:b558136536 . _:b558137970 . _:b558136556 . . _:b558136539 . _:b558137981 . _:b558137658 . _:b558136538 . _:b558137980 . . _:b558136934 . _:b558136549 . _:b558137983 . _:b558136407 . _:b558137372 . _:b558136548 . _:b558137982 . . _:b558136551 . _:b558137977 . . _:b558136550 . _:b558137976 . _:b558136784 . . _:b558136980 . . _:b558137979 . _:b558136545 . . _:b558136544 . _:b558137978 . . _:b558136429 . _:b558136547 . _:b558137989 . . _:b558136546 . _:b558137988 . _:b558136557 . _:b558137991 . _:b558136675 . _:b558136556 . _:b558137990 . _:b558136309 . _:b558136559 . _:b558137985 . _:b558136558 . _:b558137984 . _:b558136553 . _:b558137987 . _:b558136552 . _:b558137986 . . _:b558137179 . _:b558136555 . _:b558137997 . _:b558137466 . _:b558136341 . _:b558136554 . _:b558137996 . . _:b558136565 . _:b558137999 . _:b558136564 . _:b558137998 . _:b558137462 . _:b558136502 . . _:b558137993 . _:b558136567 . . . _:b558137992 . _:b558136566 . _:b558136311 . . _:b558136561 . _:b558137995 . _:b558136419 . . . _:b558136560 . _:b558137994 . . _:b558136563 . _:b558138005 . . _:b558136562 . _:b558138004 . . _:b558138069 . _:b558136573 . _:b558138007 . _:b558136242 "98"^^ . . . _:b558138006 . _:b558136572 . . . . . _:b558136575 . _:b558138001 . _:b558136252 "35"^^ . . _:b558137191 . _:b558136253 "32"^^ . _:b558136574 . _:b558138000 . _:b558136254 "31"^^ . _:b558136766 . _:b558136569 . _:b558138003 . _:b558136255 "31"^^ . _:b558136670 . . . _:b558136568 . _:b558138002 . . _:b558137988 . _:b558136597 . _:b558136571 . _:b558138013 . _:b558136570 . _:b558138012 . . _:b558136251 "36"^^ . _:b558136248 "40"^^ . _:b558136249 "38"^^ . _:b558138015 . _:b558137625 . _:b558136250 "37"^^ . _:b558138014 . . _:b558138009 . _:b558136246 "43"^^ . _:b558136247 "40"^^ . . _:b558136243 "57"^^ . . _:b558138008 . _:b558138077 . . _:b558136245 "43"^^ . . _:b558138011 . . _:b558137815 . _:b558138010 . . _:b558136244 "50"^^ . _:b558138021 . . _:b558137557 . _:b558137762 . _:b558138020 . _:b558137819 . . _:b558138023 . _:b558138022 . . _:b558138017 . _:b558137457 . _:b558137368 . . _:b558138016 . _:b558137687 . _:b558138019 . . _:b558138018 . _:b558136242 . _:b558138029 . . _:b558138149 . . _:b558138028 . . _:b558138031 . _:b558138044 . _:b558136956 . _:b558138030 . . . _:b558138025 . _:b558136787 . _:b558138024 . _:b558137452 . _:b558138027 . _:b558138026 . . _:b558138037 . . . _:b558137952 . _:b558137748 . _:b558138036 . . _:b558138039 . . . . . _:b558136941 . _:b558138038 . _:b558136518 . _:b558136259 "29"^^ . _:b558138033 . . _:b558136258 "29"^^ . _:b558137369 . _:b558138032 . . _:b558138035 . _:b558136804 . _:b558136533 . _:b558138034 . _:b558137519 . _:b558136263 "28"^^ . _:b558137993 . _:b558137937 . _:b558138045 . _:b558136262 "28"^^ . _:b558137802 . _:b558138044 . _:b558136261 "28"^^ . _:b558138047 . _:b558136519 . _:b558136260 "28"^^ . . _:b558138046 . _:b558136267 "26"^^ . _:b558137666 . _:b558138041 . _:b558136266 "27"^^ . . _:b558138040 . _:b558136265 "27"^^ . _:b558137401 . . . _:b558138043 . . _:b558136264 "27"^^ . . _:b558138042 . _:b558136270 "25"^^ . _:b558138003 . _:b558138053 . . _:b558136271 "25"^^ . _:b558137694 . _:b558138052 . _:b558137678 . . _:b558136268 "25"^^ . _:b558138055 . . _:b558136269 "25"^^ . _:b558136733 . _:b558138054 . _:b558136274 "23"^^ . _:b558138049 . . . _:b558136275 "23"^^ . _:b558138048 . . _:b558137648 . _:b558136272 "24"^^ . . _:b558138051 . _:b558136273 "24"^^ . . _:b558138050 . _:b558136278 "22"^^ . . . . _:b558136279 "22"^^ . _:b558138061 . _:b558137174 . . . _:b558138060 . . _:b558136276 "23"^^ . _:b558136277 "22"^^ . _:b558138063 . _:b558138062 . _:b558136281 "20"^^ . _:b558136673 . _:b558138057 . . . _:b558137843 . _:b558136280 "20"^^ . _:b558138056 . _:b558136276 . _:b558136283 "20"^^ . _:b558138059 . . _:b558136282 "20"^^ . _:b558136256 "30"^^ . _:b558138058 . _:b558136285 "19"^^ . _:b558136885 . _:b558136257 "30"^^ . _:b558138069 . . _:b558136284 "20"^^ . _:b558136287 "18"^^ . _:b558138068 . . _:b558138071 . _:b558137492 . _:b558136286 "19"^^ . _:b558136544 . _:b558138070 . _:b558137495 . _:b558136289 "18"^^ . _:b558136288 "18"^^ . _:b558138065 . . _:b558138064 . _:b558137159 . _:b558136290 "17"^^ . . _:b558138067 . _:b558136291 "17"^^ . _:b558136621 . _:b558138066 . . _:b558137344 . _:b558136292 "16"^^ . _:b558137902 . _:b558138077 . . . _:b558136293 "16"^^ . _:b558138076 . _:b558136294 "16"^^ . _:b558137027 . . _:b558138079 . _:b558136295 "16"^^ . _:b558137573 . . _:b558138078 . _:b558136296 "16"^^ . . _:b558138073 . _:b558136297 "16"^^ . _:b558137032 . _:b558138072 . _:b558136298 "16"^^ . _:b558138001 . _:b558138075 . . _:b558136299 "16"^^ . . _:b558138074 . _:b558136635 . _:b558136300 "15"^^ . . _:b558138085 . _:b558136301 "15"^^ . _:b558138092 . _:b558137263 . _:b558137384 . _:b558138084 . _:b558136302 "15"^^ . _:b558138087 . _:b558136303 "15"^^ . _:b558136380 . . _:b558138086 . _:b558136304 "15"^^ . _:b558136513 . . _:b558138081 . _:b558136305 "15"^^ . . _:b558138080 . _:b558136306 "15"^^ . _:b558136921 . _:b558138083 . _:b558136307 "15"^^ . . _:b558138082 . _:b558136308 "15"^^ . . . _:b558136309 "14"^^ . _:b558138093 . _:b558136310 "14"^^ . _:b558138092 . . . _:b558136311 "14"^^ . _:b558138095 . . _:b558136903 . _:b558138094 . _:b558136312 "14"^^ . . _:b558136319 "13"^^ . _:b558136313 "14"^^ . _:b558138089 . . . _:b558136318 "13"^^ . _:b558136314 "14"^^ . _:b558138088 . _:b558136317 "13"^^ . _:b558136315 "14"^^ . _:b558138091 . _:b558137622 . _:b558136316 "14"^^ . _:b558138090 . _:b558138101 . . . _:b558138104 . _:b558138100 . . _:b558136370 . _:b558138103 . _:b558138102 . . . _:b558138097 . . _:b558138096 . _:b558138099 . . _:b558137755 . . _:b558138098 . _:b558138109 . _:b558137129 . . _:b558138108 . _:b558138111 . . _:b558138110 . _:b558138105 . _:b558138104 . . _:b558138107 . _:b558136626 . . _:b558138106 . . . . _:b558136460 . . _:b558137605 . _:b558137323 . _:b558137604 . . . _:b558137613 . _:b558136436 . . _:b558136645 . _:b558137607 . . _:b558136987 . _:b558137606 . _:b558137808 . _:b558138153 . _:b558137072 . _:b558137601 . _:b558137600 . . _:b558137326 . . _:b558137707 . . _:b558137603 . . . _:b558136349 . . . _:b558137602 . . _:b558136759 . _:b558137613 . . _:b558137161 . _:b558137612 . . _:b558136577 . _:b558137615 . _:b558137727 . . _:b558137614 . _:b558137211 . _:b558136355 . _:b558137609 . _:b558137608 . _:b558136846 . _:b558137419 . _:b558137611 . _:b558137610 . . _:b558137621 . _:b558137620 . . _:b558138000 . _:b558137730 . _:b558137623 . _:b558136550 . _:b558137622 . . _:b558137617 . . _:b558137616 . _:b558136403 . _:b558137619 . . . _:b558137618 . _:b558136284 . _:b558136450 . _:b558137668 . _:b558137629 . _:b558137395 . . _:b558137628 . . _:b558137631 . _:b558137058 . _:b558137630 . . . _:b33179867 "In comparison, we re-analyzed coverage breadth in single cells sequenced by MALBAC>>19<< using unique reads and calculated 69.54% coverage breadth." . _:b558137625 . . . . . _:b558137624 . _:b558137367 . . _:b558136316 . _:b558137627 . _:b558137560 . . _:b558137626 . _:b558137637 . _:b558137636 . . _:b558137639 . . _:b558137150 . . _:b558137638 . . . _:b558137339 . _:b558137633 . . _:b558137632 . _:b558137635 . _:b558137925 . . _:b558137634 . . . _:b558137645 . . _:b558137644 . _:b33179884 . _:b558137647 . . _:b558137646 . _:b558137641 . _:b558137640 . _:b558138016 . _:b558137643 . . _:b558137408 . _:b558137642 . . . . . _:b558137653 . _:b558136925 . _:b558137652 . . _:b558137655 . _:b558137654 . . . _:b558136602 . _:b558137649 . . _:b33179877 "population and single nuclei sequencing of a tnbc" . _:b558137648 . . _:b558136600 . . . _:b558137651 . _:b558136453 . _:b558138022 . . . _:b558137650 . _:b558137057 . _:b558137661 . _:b558136266 . . _:b558136652 . _:b558137959 . _:b558137660 . _:b33179859 "This approach provides an advantage over using chemical inhibitors to induce polyploidy in single cells>>12<<,13 because it does not require live cells." . . . _:b558137663 . _:b558138057 . _:b558136803 . _:b558137662 . _:b558137657 . _:b558137656 . . . . _:b558137659 . _:b558136487 . _:b558137658 . _:b558137669 . _:b558136853 . _:b558137668 . _:b558137671 . . _:b558137520 . . _:b558137670 . _:b558137803 . . _:b558137665 . . _:b558137664 . _:b558137245 . _:b33179876 . . _:b558137667 . . _:b558136963 . _:b558137274 . _:b558137666 . . _:b558137734 . _:b558136409 . _:b558137677 . . _:b558137381 . . _:b558137676 . . _:b558136245 . _:b558137679 . _:b558136244 . _:b558137678 . _:b558137607 . . _:b558136247 . _:b558137673 . _:b558137593 . _:b558136586 . _:b558137672 . . _:b558136246 . _:b558137675 . . _:b558138100 . _:b558137674 . _:b558136891 . _:b558136243 . _:b558137685 . _:b558137089 . . . _:b558137651 . _:b558136242 . _:b558137684 . . _:b558136253 . _:b558137687 . _:b558136252 . _:b558137686 . _:b558137530 . . _:b558136255 . _:b558137681 . . _:b558136254 . _:b558137680 . _:b558136249 . _:b558137683 . _:b558137069 . _:b558137948 . _:b558136248 . _:b558137682 . _:b558136251 . _:b558137693 . _:b558137163 . . . . _:b558136250 . _:b558137692 . . _:b558137861 "2"^^ . . _:b558136261 . _:b558137695 . . _:b558137391 . _:b558137860 "2"^^ . _:b558136260 . _:b558137694 . _:b558136260 . _:b558137863 "2"^^ . _:b558136263 . _:b558137689 . . _:b558136740 . _:b558137862 "2"^^ . _:b558136262 . _:b558137688 . _:b558137674 . _:b558138166 . _:b558137857 "2"^^ . _:b558136257 . _:b558137691 . _:b558136976 . _:b558137856 "2"^^ . _:b558136256 . _:b558137690 . _:b558137859 "2"^^ . _:b558136259 . _:b558137701 . _:b558136777 . _:b558137858 "2"^^ . _:b558136258 . _:b558137700 . _:b558137869 "2"^^ . . . _:b558136780 . _:b558137703 . _:b558136269 . _:b558137868 "2"^^ . _:b558136268 . _:b558137702 . _:b558137871 "2"^^ . _:b558136271 . _:b558137697 . . _:b558137870 "2"^^ . _:b558136270 . _:b558137696 . . _:b558137865 "2"^^ . _:b558136265 . _:b558137699 . _:b558137864 "2"^^ . _:b558136264 . _:b558137698 . _:b558137867 "2"^^ . _:b558136267 . _:b558137709 . _:b558137866 "2"^^ . _:b558136431 . _:b558137708 . _:b558136266 . . _:b558137877 "2"^^ . . . _:b558137711 . _:b558136277 . . _:b558137876 "2"^^ . _:b558137464 . _:b558136276 . _:b558137710 . . _:b558137879 "2"^^ . _:b558136279 . _:b558137705 . _:b558137878 "2"^^ . _:b558136278 . _:b558137704 . _:b33179868 . _:b558137873 "2"^^ . _:b558138035 . . _:b558137253 . _:b33179845 "discussion" . _:b558136273 . _:b558137707 . _:b558137872 "2"^^ . _:b558136272 . _:b558137706 . . _:b558137875 "2"^^ . _:b558136275 . _:b558137717 . _:b558137874 "2"^^ . _:b558136274 . _:b558137716 . . _:b558137885 "2"^^ . _:b558136285 . _:b558137719 . _:b558137884 "2"^^ . . _:b558136284 . _:b558137718 . _:b33179866 . _:b558137887 "2"^^ . . _:b558136287 . _:b558137713 . . _:b558137270 . _:b558137234 . _:b558137886 "2"^^ . _:b558137892 . _:b558136286 . _:b558137712 . _:b558137881 "2"^^ . _:b558136281 . _:b558137739 . _:b558137715 . . _:b558137880 "2"^^ . . . _:b558136280 . _:b558137714 . . . _:b558137883 "2"^^ . . _:b558136283 . _:b558137725 . . _:b558137882 "2"^^ . _:b558136294 . _:b558137724 . _:b558136282 . _:b558137893 "2"^^ . _:b558136293 . _:b558137727 . . _:b558137892 "2"^^ . _:b558136292 . _:b558137726 . _:b558136443 . _:b558137895 "2"^^ . _:b558136295 . _:b558137721 . _:b558137894 "2"^^ . _:b558137101 . _:b558136294 . _:b558137720 . . _:b558136720 . _:b558137889 "2"^^ . _:b558136289 . _:b558137723 . . . . _:b558137888 "2"^^ . _:b558136288 . _:b558137722 . _:b558136245 . _:b558137891 "2"^^ . . _:b558136344 . _:b558136291 . _:b558137733 . _:b558137282 . _:b558137508 . _:b558137890 "2"^^ . _:b558136290 . _:b558137732 . . _:b558136950 . _:b558137901 "2"^^ . . _:b558136301 . _:b558137735 . _:b558137900 "2"^^ . _:b558136300 . _:b558137734 . . _:b558137903 "2"^^ . _:b558136303 . _:b558137729 . _:b558137090 . . _:b558137902 "2"^^ . . . _:b558136302 . _:b558137728 . _:b558136395 . _:b558137393 . _:b558137897 "2"^^ . _:b558137528 . _:b558137853 . _:b558136297 . _:b558138012 . _:b558137731 . . _:b558137896 "2"^^ . _:b558136296 . _:b558137730 . . _:b558137899 "2"^^ . _:b558137286 . _:b558136299 . _:b558137741 . _:b558137235 . _:b558137898 "2"^^ . _:b558138051 . _:b558136298 . _:b558137740 . _:b558137909 "2"^^ . _:b558138124 . . _:b558137076 . . _:b558137743 . _:b558136309 . _:b558137908 "2"^^ . _:b558136308 . _:b558137742 . . _:b558137911 "2"^^ . _:b558137105 . . _:b558136311 . _:b558137737 . _:b558137496 . . _:b558137910 "2"^^ . _:b558136310 . _:b558137736 . _:b558137905 "2"^^ . . _:b558136305 . _:b558137739 . _:b558137904 "2"^^ . _:b558136304 . _:b558137738 . . _:b558137907 "2"^^ . _:b558136307 . _:b558137749 . _:b558137788 . _:b558137906 "2"^^ . . _:b33179866 "We also performed Single-Nucleus-Sequencing (SNS)11,>>18<< on 50 single SK-BR-3 cells and calculated copy number profiles at 220kb resolution, which showed that the major amplifications of MET, MYC, ERBB2, BCAS1 and a deletion in DCC were stable (mean R2 = 0.91) in all of the 50 cells (Fig." . _:b558136306 . _:b558137748 . _:b558137917 "2"^^ . _:b558136317 . _:b558137970 . _:b558137751 . _:b558137289 . _:b558137916 "2"^^ . _:b558136316 . _:b558137750 . _:b558137919 "2"^^ . _:b558136319 . _:b558137745 . _:b558137312 . _:b558137436 . _:b558137918 "2"^^ . _:b558137940 . _:b558136318 . _:b558137744 . . _:b33179861 "input four (or more) copies of each single cell genome for whole-genome-amplification (WGA) to decrease the allelic dropout and false positive error rates, which are major sources of error during multiple-displacement-amplification (MDA)>>14<<,15. Additionally, we limit the MDA time to 80 minutes to mitigate FP errors associated with the infidelity of the \u03D529 polymerase (Supplementary Methods)." . _:b558137913 "2"^^ . _:b558136313 . _:b558137747 . . _:b558137912 "2"^^ . _:b558136312 . _:b558137746 . _:b558137915 "2"^^ . _:b558136315 . _:b558137757 . _:b558137914 "2"^^ . _:b558137184 . _:b558137376 . _:b558136314 . _:b558137756 . . _:b558137925 "2"^^ . _:b558137759 . . . _:b558137924 "2"^^ . . . _:b558137758 . . _:b558137927 "2"^^ . _:b558137399 . _:b558137753 . . _:b558137926 "2"^^ . _:b558137752 . _:b558137921 "2"^^ . _:b558137755 . _:b558137920 "2"^^ . . _:b558137754 . _:b558137923 "2"^^ . _:b558138014 . _:b558137765 . _:b558136944 . _:b558137922 "2"^^ . _:b558137764 . _:b558137933 "2"^^ . _:b558137277 . _:b558137767 . . _:b558137932 "2"^^ . . _:b558137766 . _:b558137935 "2"^^ . _:b558137017 . _:b558137354 . _:b558137761 . _:b558137934 "2"^^ . _:b558136686 . . _:b558137760 . . _:b33179848 "This model has also been supported by bulk sequencing data in prostate cancer29 and in rearrangement patterns called firestorms30 or chromothripsis>>31<<. A punctuated model is consistent with the mechanisms that underlie CNAs, including chromosome missegregation32, cytokinesis defects and breakage-fusion-bridge33, which can generate complex rearrangements in just a few cell divisions. In" . _:b558137929 "2"^^ . . _:b558137763 . _:b558137928 "2"^^ . . _:b558137448 . _:b558137762 . _:b558137931 "2"^^ . _:b558137773 . _:b558137194 . _:b558137930 "2"^^ . _:b558136359 . . _:b558137772 . _:b558137941 "2"^^ . _:b558136882 . _:b558137775 . . _:b558137940 "2"^^ . _:b558137774 . _:b558137943 "2"^^ . . _:b558137769 . _:b558136812 . _:b558137942 "2"^^ . . _:b558137768 . _:b558137937 "2"^^ . _:b558137771 . _:b558137936 "2"^^ . _:b558137770 . _:b558138050 . _:b558137939 "2"^^ . . _:b558137953 . _:b558137781 . _:b558137912 . _:b558137938 "2"^^ . _:b558137780 . _:b558137269 . _:b558137949 "2"^^ . _:b558137783 . _:b558137831 . _:b558137948 "2"^^ . _:b558136498 . _:b558137782 . _:b558137951 "2"^^ . _:b558136284 . _:b558136285 . _:b558137777 . _:b558136286 . _:b558136287 . _:b558137950 "2"^^ . _:b558136280 . _:b558136281 . _:b558137776 . _:b558136282 . _:b558136283 . _:b558137945 "2"^^ . . _:b558136276 . _:b558136277 . _:b558138072 . _:b558137779 . _:b558136278 . . _:b558136279 . _:b558137944 "2"^^ . _:b558136272 . _:b558136273 . _:b558137778 . _:b558137273 . _:b558136274 . _:b558136275 . _:b558137947 "2"^^ . _:b558136268 . . _:b558137789 . _:b558136269 . _:b558136270 . _:b558136271 . _:b558137946 "2"^^ . _:b558136264 . _:b558136265 . _:b558137788 . _:b558136266 . _:b558136267 . _:b558137957 "2"^^ . _:b558136260 . . _:b558137791 . _:b558136261 . _:b558136262 . _:b558137981 . _:b558136263 . _:b558137956 "2"^^ . _:b558136256 . _:b558136257 . _:b558137790 . _:b558136258 . . _:b558137959 "2"^^ . . _:b558136259 . _:b558136316 . _:b558138024 . _:b558136317 . _:b558137785 . _:b558136318 . _:b558136319 . _:b558137958 "2"^^ . _:b558136312 . _:b558136313 . _:b558137784 . _:b558137229 . _:b558136314 . . _:b558136315 . _:b558137953 "2"^^ . _:b558136308 . _:b558136309 . _:b558137846 . _:b558137787 . _:b558136310 . _:b558136311 . _:b558137952 "2"^^ . _:b558136304 . _:b558136305 . _:b558137786 . _:b558136306 . _:b558137333 . _:b558136307 . _:b558137955 "2"^^ . _:b558136300 . _:b558136301 . _:b558137797 . _:b558136302 . _:b558136303 . _:b558137954 "2"^^ . _:b558136296 . . _:b558136297 . _:b558137796 . _:b558136298 . _:b558136299 . _:b558137965 "2"^^ . _:b558136292 . _:b558136293 . _:b558137799 . _:b558136294 . _:b558136295 . _:b558137964 "2"^^ . . _:b558136288 . _:b558136806 . _:b558137798 . _:b558136289 . _:b558136290 . _:b558136291 . _:b558137967 "2"^^ . _:b558137749 . . _:b558137793 . _:b558137966 "2"^^ . . _:b558137792 . _:b558137961 "2"^^ . _:b558136830 . _:b558137795 . _:b558137960 "2"^^ . . _:b558137794 . _:b558137463 . . _:b558137963 "2"^^ . _:b558137805 . _:b558137982 . _:b558137962 "2"^^ . _:b558137804 . _:b558137973 "2"^^ . _:b558137807 . _:b558137654 . _:b558137146 . _:b558137972 "2"^^ . _:b558136351 . _:b558137806 . . _:b558137975 "2"^^ . _:b558136252 . . _:b558136253 . _:b558137801 . _:b558136254 . _:b558136255 . _:b558137974 "2"^^ . _:b558136248 . _:b558136249 . _:b558137800 . _:b558136250 . _:b558136251 . _:b558137969 "2"^^ . _:b558136244 . _:b558136245 . _:b558137803 . _:b558136246 . _:b558136247 . _:b558137968 "2"^^ . _:b558137802 . _:b558136242 . _:b558136243 . _:b558137971 "2"^^ . _:b558137314 . . . _:b558137813 . . _:b558137970 "2"^^ . _:b558137812 . _:b558137981 "2"^^ . . _:b558136696 . _:b558138132 . _:b558137815 . . _:b558136625 . _:b558137980 "2"^^ . _:b558137814 . _:b558137983 "2"^^ . . _:b558137809 . . _:b558137982 "2"^^ . . _:b558137808 . _:b558137977 "2"^^ . _:b558137811 . . _:b558137976 "2"^^ . _:b558136350 . _:b558137810 . _:b558137979 "2"^^ . _:b558137821 . _:b558137978 "2"^^ . _:b558137820 . _:b558137931 . _:b558137989 "2"^^ . _:b558137823 . _:b558136456 . . _:b558137988 "2"^^ . _:b558137822 . _:b558137991 "2"^^ . . _:b558137817 . . _:b558137990 "2"^^ . _:b558137816 . . _:b558137985 "2"^^ . . _:b558137416 . _:b558137819 . _:b558137373 . . _:b558137984 "2"^^ . _:b558137818 . _:b558137987 "2"^^ . _:b558137164 . _:b558137829 . _:b558137240 . _:b558137986 "2"^^ . _:b558137828 . _:b558137997 "2"^^ . _:b558136428 . _:b558137831 . _:b558137996 "2"^^ . . _:b558137830 . _:b558137048 . _:b558138113 . _:b558137999 "2"^^ . . _:b558137825 . . _:b558137998 "2"^^ . _:b558137824 . _:b558137993 "2"^^ . . . _:b558137827 . . _:b558137992 "2"^^ . . _:b558137065 . _:b558137826 . _:b558137995 "2"^^ . . _:b558137837 . _:b558137994 "2"^^ . _:b558138103 . _:b558137836 . _:b558136899 . _:b558138005 "2"^^ . . _:b558137839 . . _:b558138004 "2"^^ . _:b558137659 . _:b558137838 . _:b558138007 "2"^^ . . . _:b558137833 . . _:b558138006 "2"^^ . _:b558137832 . . _:b558138001 "2"^^ . _:b558136664 . . _:b558137835 . _:b558136703 . _:b558138000 "2"^^ . _:b558136360 . _:b558137834 . _:b558138003 "2"^^ . _:b558137845 . _:b558138002 "2"^^ . . . . _:b558137844 . _:b558138013 "2"^^ . . _:b558137847 . _:b558138012 "2"^^ . _:b558137846 . _:b558138015 "2"^^ . _:b558136540 . _:b558137418 . . _:b558137841 . _:b558136541 . _:b558136542 . _:b558136543 . _:b558138056 . _:b558138014 "2"^^ . _:b558137746 . _:b558136271 . _:b558136536 . . _:b558137840 . _:b558136537 . _:b558136538 . _:b558136539 . _:b558138009 "2"^^ . _:b558136532 . . _:b558136533 . _:b558137843 . _:b558136534 . _:b558136535 . _:b558138008 "2"^^ . _:b558136528 . _:b558136529 . _:b558137842 . . _:b558136530 . _:b558136531 . _:b558138011 "2"^^ . _:b558136524 . _:b558136525 . _:b558137853 . _:b558136526 . _:b558136527 . _:b558138010 "2"^^ . _:b558137224 . . _:b558136520 . _:b558136521 . _:b558137852 . _:b558136522 . _:b558136523 . _:b558138021 "2"^^ . _:b558136516 . _:b558136517 . _:b558137855 . _:b558136518 . _:b558136519 . _:b558138053 . _:b558138020 "2"^^ . . _:b558136512 . . _:b558137854 . . _:b558136513 . _:b558136514 . . _:b558136515 . _:b558138023 "2"^^ . _:b558136572 . . _:b558137849 . _:b558136573 . _:b558136574 . _:b558136575 . _:b558138022 "2"^^ . . _:b558136568 . _:b558136569 . _:b558137848 . _:b558136570 . _:b558136571 . _:b33179868 "We evaluated coverage uniformity using Lorenz curves20 which showed highly uniform coverage, representing a major improvement over our previous SNS method11,>>18<< and is equivalent to the MALBAC data19 (Fig." . _:b558138017 "2"^^ . _:b558136564 . _:b558136565 . _:b558137851 . _:b558136566 . _:b558137305 . _:b558136567 . _:b558138016 "2"^^ . _:b558136560 . _:b558136561 . _:b558137850 . _:b558136562 . _:b558136563 . _:b558138019 "2"^^ . _:b558136556 . _:b558136557 . _:b558137876 . _:b558137349 . _:b558136558 . _:b558136559 . _:b558138018 "2"^^ . . . _:b558136552 . _:b558136553 . _:b558137348 . _:b558136554 . _:b558136555 . _:b558138029 "2"^^ . _:b558136548 . _:b558136549 . _:b558137351 . _:b558136550 . _:b558137531 . . _:b558138028 "2"^^ . _:b558136279 . _:b558136551 . _:b558136544 . . _:b558137350 . _:b558136545 . _:b558136546 . . _:b558136547 . _:b558138031 "2"^^ . _:b558136476 . _:b558136477 . _:b558137345 . _:b558136478 . . _:b558138030 "2"^^ . _:b558136479 . _:b558136472 . . _:b558137344 . _:b558136473 . _:b558136474 . _:b558137182 . _:b558136475 . _:b558138025 "2"^^ . _:b558136468 . _:b558136469 . _:b558137347 . _:b558136470 . _:b558136471 . _:b558138024 "2"^^ . _:b558136464 . _:b558136465 . _:b558137346 . _:b558136466 . _:b558137599 . _:b558136467 . _:b558138027 "2"^^ . _:b558136460 . . _:b558137357 . _:b558137283 . _:b558136461 . _:b558136462 . _:b558136463 . _:b558138026 "2"^^ . _:b558136456 . _:b558136457 . _:b558137965 . _:b558137356 . _:b558136458 . . _:b558136459 . _:b558138037 "2"^^ . _:b558136452 . _:b558136453 . _:b558137359 . _:b558136863 . . _:b558136454 . _:b558136455 . _:b558138036 "2"^^ . _:b558136448 . _:b558136449 . _:b558137420 . _:b558137358 . _:b558136450 . _:b558136451 . _:b558138039 "2"^^ . _:b558136508 . _:b558136509 . _:b558137353 . . . _:b558136510 . . _:b558138038 "2"^^ . _:b558136511 . _:b558136504 . . _:b558137352 . _:b558136505 . _:b558136506 . _:b558136636 . _:b558136507 . _:b558138033 "2"^^ . _:b558137197 . _:b558136500 . _:b558137380 . _:b558136501 . _:b558137355 . _:b558136502 . _:b558136503 . _:b558138032 "2"^^ . _:b558136496 . _:b558138090 . _:b558136508 . _:b558137354 . _:b558136497 . . _:b558137972 . _:b558136498 . _:b558136499 . _:b558138035 "2"^^ . _:b558136492 . _:b558136493 . _:b558137365 . _:b558136494 . _:b558136495 . _:b558138034 "2"^^ . _:b558136488 . _:b558136489 . _:b558137364 . _:b558137080 . _:b558136490 . _:b558136491 . _:b558138045 "2"^^ . _:b558137834 . _:b558136484 . _:b558136485 . _:b558137367 . . _:b558136486 . _:b558136487 . _:b558138044 "2"^^ . _:b558137303 . _:b558136480 . _:b558136481 . _:b558137366 . . _:b558136482 . _:b558136483 . _:b558138047 "2"^^ . _:b558136412 . . _:b558136413 . _:b558137361 . _:b558136414 . _:b558136415 . _:b558138046 "2"^^ . _:b558136408 . _:b558136409 . _:b558137360 . _:b558136410 . _:b558137704 . _:b558136411 . _:b558138041 "2"^^ . _:b558136404 . _:b558136405 . _:b558137363 . _:b558136728 . _:b558136406 . _:b558136407 . _:b558138041 . _:b558138040 "2"^^ . _:b558136400 . _:b558136401 . _:b558137362 . _:b558136402 . . _:b558136403 . _:b558138043 "2"^^ . _:b558137471 . _:b558136396 . _:b558137670 . _:b558136397 . _:b558137373 . . _:b558136398 . _:b558136399 . _:b558138042 "2"^^ . . _:b558136392 . _:b558136393 . _:b558137372 . _:b558136394 . _:b558136395 . _:b558138053 "2"^^ . . _:b558136388 . _:b558136389 . _:b558137375 . _:b558136390 . _:b558136291 . _:b558138052 "2"^^ . _:b558136391 . _:b558136384 . _:b558136470 . _:b558137374 . _:b558136385 . . _:b558136386 . _:b558136387 . _:b558138055 "2"^^ . _:b558136444 . _:b558138089 . _:b558136445 . _:b558137369 . _:b558136446 . _:b558136447 . _:b558138054 "2"^^ . _:b558136440 . _:b558136441 . _:b558137792 . _:b558137368 . _:b558136442 . . _:b558136443 . _:b558138049 "2"^^ . _:b558136436 . _:b558136437 . _:b558137371 . _:b558136438 . _:b558136439 . _:b558138048 "2"^^ . _:b558137195 . _:b558136432 . _:b558136433 . _:b558137930 . _:b558137370 . _:b558136434 . _:b558136435 . _:b558138051 "2"^^ . . _:b558137175 . _:b558136428 . _:b558136429 . _:b558137381 . . _:b558136430 . _:b558136431 . _:b558138050 "2"^^ . . _:b558136424 . _:b558138157 . _:b558136745 . _:b558136425 . _:b558137380 . _:b558136426 . _:b558136427 . _:b558138061 "2"^^ . . _:b558136420 . _:b558136421 . _:b558137383 . _:b558136422 . _:b558136423 . _:b558138060 "2"^^ . _:b558136416 . . _:b558136417 . _:b558137382 . _:b558136418 . _:b558136419 . _:b558138063 "2"^^ . _:b558136348 . _:b558136349 . _:b558137377 . _:b558136350 . _:b558136351 . _:b558138062 "2"^^ . _:b558136344 . . . _:b558137933 . _:b558137376 . _:b558136345 . _:b558136346 . . _:b558138057 "2"^^ . _:b558136347 . _:b558136340 . _:b558136341 . _:b558137753 . _:b558137379 . _:b558136342 . _:b558137035 . . _:b558138056 "2"^^ . _:b558136343 . _:b558136336 . _:b558136337 . _:b558137649 . _:b558137378 . _:b558136338 . _:b558136249 . _:b558138059 "2"^^ . _:b558136339 . _:b558136332 . _:b558136333 . _:b33179849 . _:b558137389 . _:b558136334 . _:b558136335 . _:b558138058 "2"^^ . _:b558136328 . . _:b558137388 . _:b558136329 . _:b558136330 . _:b558137879 . _:b558136632 . _:b558138069 "2"^^ . _:b558136331 . . . _:b558136324 . . _:b558137391 . _:b558136325 . _:b558136326 . _:b558136327 . _:b558138068 "2"^^ . _:b558136320 . _:b558136321 . _:b558137390 . _:b558136348 . _:b558136322 . _:b558136323 . _:b558138071 "2"^^ . _:b558136380 . _:b558136381 . _:b558137385 . _:b558136382 . _:b558136383 . _:b558138070 "2"^^ . _:b558136376 . _:b558136377 . _:b558137384 . _:b558136378 . . _:b558138065 "2"^^ . _:b558136379 . _:b558136372 . _:b558136373 . _:b558137387 . _:b558136374 . _:b558136375 . _:b558138064 "2"^^ . _:b558136368 . . _:b558137594 . _:b558137386 . _:b558137232 . _:b558136369 . _:b558136370 . _:b558136371 . _:b558138067 "2"^^ . _:b558137501 . _:b558136364 . _:b558136365 . _:b558137397 . _:b558136366 . _:b558136367 . _:b558138066 "2"^^ . . _:b558136360 . . _:b558136361 . _:b558137396 . _:b558136362 . _:b558136363 . _:b558138077 "2"^^ . _:b558136356 . _:b558137063 . _:b558136357 . _:b558137399 . _:b558136358 . . _:b558138076 "2"^^ . _:b558136359 . _:b558136352 . . _:b558136353 . _:b558137398 . . _:b558136354 . _:b558136355 . _:b558138079 "2"^^ . _:b558136796 . _:b558136432 . _:b558137393 . _:b558136797 . _:b558136371 . . _:b558136798 . . _:b558136799 . _:b558138078 "2"^^ . _:b558136792 . _:b558136793 . _:b558137392 . _:b558136794 . _:b558136264 . _:b558138073 "2"^^ . _:b558136795 . _:b558136788 . _:b558136789 . _:b558137395 . _:b558136551 . _:b558136790 . _:b33179864 "validation in a monoclonal cancer cell line" . _:b558138072 "2"^^ . _:b558136791 . _:b558136784 . . _:b558136785 . _:b558137394 . _:b558136786 . _:b558137873 . _:b558136787 . _:b558138075 "2"^^ . _:b558136780 . . _:b558137405 . . _:b558136781 . _:b558136782 . _:b558136783 . _:b558138074 "2"^^ . _:b558136776 . _:b558136777 . _:b558137404 . _:b558136778 . _:b558136779 . _:b558138085 "2"^^ . _:b558136772 . _:b558136993 . _:b558136773 . _:b558137407 . _:b558136735 . . _:b558136774 . . . _:b558136775 . _:b558138084 "2"^^ . . _:b558136768 . _:b558137984 . . _:b558137406 . _:b558136769 . . _:b558136770 . _:b558136771 . _:b558138087 "2"^^ . _:b558137162 . _:b558136828 . _:b558136829 . _:b558137401 . _:b558136830 . _:b558136831 . _:b558138086 "2"^^ . _:b558137426 . _:b558136824 . _:b558136825 . _:b558137400 . . . _:b558136826 . _:b558136827 . _:b558138081 "2"^^ . _:b558137051 . _:b558136820 . _:b558136821 . _:b558137403 . _:b558136822 . _:b558136823 . _:b558138080 "2"^^ . _:b558136646 . _:b558136816 . _:b558136817 . _:b558137719 . _:b558137402 . _:b558136818 . _:b558136819 . _:b558138083 "2"^^ . _:b558137995 . _:b558136812 . _:b558136813 . _:b558137413 . _:b558136814 . _:b558137383 . _:b558136815 . _:b558138082 "2"^^ . _:b558137829 . _:b558136808 . _:b558136297 . _:b558137412 . _:b558136809 . _:b558136810 . _:b558136811 . _:b558138093 "2"^^ . _:b558136643 . _:b558136501 . _:b558136804 . _:b558136805 . _:b558137415 . _:b558136806 . _:b558136807 . _:b558138092 "2"^^ . _:b558136800 . _:b558136801 . _:b558137414 . _:b558136802 . _:b558136803 . _:b558138095 "2"^^ . _:b558136732 . _:b558136733 . _:b558137409 . _:b558136734 . _:b558136735 . _:b558138094 "2"^^ . _:b558136728 . _:b558136729 . _:b558137408 . _:b558136730 . _:b558136731 . _:b558138089 "2"^^ . _:b558136724 . _:b558136725 . _:b558137411 . . _:b558136726 . _:b558136727 . _:b558138088 "2"^^ . _:b558136720 . _:b558136721 . _:b558137410 . _:b558136433 . _:b558136722 . _:b558136723 . _:b558138091 "2"^^ . . _:b558136465 . _:b558136716 . _:b558136717 . _:b558137421 . . . _:b558136718 . . . _:b558138090 "2"^^ . _:b558136719 . _:b558136712 . _:b558136713 . _:b558137420 . _:b558136714 . _:b558136715 . _:b558138101 "2"^^ . _:b558136708 . _:b558136709 . _:b558137423 . _:b558136418 . _:b558136710 . _:b558136711 . _:b558138100 "2"^^ . _:b558136704 . _:b558136705 . _:b558137422 . _:b558136706 . . _:b558138103 "2"^^ . _:b558136707 . . . _:b558136764 . _:b558136765 . _:b558137417 . _:b558136766 . _:b558136767 . _:b558138102 "2"^^ . _:b558136760 . _:b558136761 . _:b558137416 . . _:b558136762 . . _:b558136929 . _:b558136763 . _:b558138097 "2"^^ . _:b558136756 . . _:b558137419 . _:b558136757 . _:b558136758 . _:b558136759 . _:b558138096 "2"^^ . _:b558136752 . _:b558136753 . _:b558137418 . _:b558136754 . _:b558137652 . _:b558137301 . . _:b558138099 "2"^^ . _:b558136755 . _:b558136748 . _:b558136749 . _:b558137429 . _:b558136750 . . _:b558136751 . _:b558138098 "2"^^ . _:b558136744 . _:b558136745 . _:b558137428 . . _:b558136746 . _:b558136747 . _:b558138109 "2"^^ . . _:b558136740 . . _:b558137431 . _:b558136741 . _:b558136273 . . _:b558136585 . _:b558136742 . _:b558136743 . _:b558138108 "2"^^ . _:b558136736 . . _:b558137430 . _:b558136737 . _:b558136738 . _:b558136739 . _:b558138111 "2"^^ . _:b558136668 . _:b558136764 . _:b558137425 . _:b558137147 . _:b558136669 . _:b558136670 . . _:b558138110 "2"^^ . _:b558136671 . _:b558136664 . _:b558136665 . _:b558137424 . . _:b558136666 . _:b558136667 . _:b558138105 "2"^^ . _:b558136660 . . _:b558136661 . _:b558137427 . . . _:b558136662 . _:b558136663 . _:b558138104 "2"^^ . . _:b558137002 . _:b558136656 . _:b558136657 . _:b33179857 . _:b558137954 . _:b558137426 . _:b558136658 . _:b558136659 . _:b558138107 "2"^^ . _:b558137958 . _:b558136652 . _:b558136653 . _:b558137437 . _:b558136654 . _:b558137597 . _:b558136655 . _:b558138106 "2"^^ . . _:b558137066 . _:b558136648 . _:b558136649 . _:b558137436 . _:b558136650 . _:b558136651 . _:b558138117 "2"^^ . _:b558136644 . _:b558136645 . _:b558137439 . _:b558136646 . . _:b558138116 "2"^^ . _:b558136647 . _:b558136640 . _:b558136641 . _:b558137438 . _:b558136642 . _:b558136643 . _:b558138119 "2"^^ . _:b558137708 . _:b558136700 . _:b558136701 . _:b558137433 . _:b558136702 . _:b558136703 . _:b558138118 "2"^^ . _:b558136696 . _:b558136697 . _:b558137432 . _:b558136698 . _:b558136699 . _:b558138113 "2"^^ . _:b558136692 . _:b558136693 . _:b558137435 . _:b558136694 . _:b558136877 . _:b558138112 "2"^^ . _:b558136695 . _:b558136688 . . _:b558137904 . _:b558137434 . _:b558136689 . _:b558136690 . _:b558136691 . _:b558138115 "2"^^ . _:b558136684 . _:b558136685 . _:b558137445 . . _:b558136686 . . _:b558138114 "2"^^ . _:b558136687 . _:b558136680 . _:b558136681 . _:b558138052 . _:b558137444 . _:b558136682 . _:b558137103 . _:b558136683 . _:b558138125 "2"^^ . _:b558136676 . _:b558136677 . _:b558137447 . _:b558136678 . _:b558136679 . _:b558138124 "2"^^ . _:b558136672 . . _:b558136673 . _:b558137446 . _:b558136674 . _:b558136675 . _:b558138127 "2"^^ . _:b558136604 . . _:b558136605 . _:b558137441 . _:b558136606 . _:b558137899 . _:b558136930 . _:b558138126 "2"^^ . _:b558136607 . _:b558136600 . . _:b558136601 . _:b558137676 . _:b558137440 . _:b558136602 . _:b558136603 . _:b558138121 "2"^^ . _:b558136596 . _:b558136597 . _:b558137443 . _:b558136598 . _:b558136599 . _:b558138120 "2"^^ . _:b558136592 . _:b558136593 . _:b558137442 . _:b558136607 . _:b558136594 . _:b558136595 . _:b558138123 "2"^^ . _:b558136588 . _:b558136589 . _:b558137453 . _:b558136590 . _:b558136591 . _:b558138122 "2"^^ . _:b558136584 . _:b558136585 . _:b558137452 . _:b558136586 . _:b558136587 . _:b558138133 "2"^^ . _:b558136580 . _:b558136581 . _:b558137455 . _:b558136582 . _:b558136583 . _:b558138132 "2"^^ . _:b558136576 . _:b558136577 . _:b558137454 . _:b558136578 . _:b558136579 . _:b558138135 "2"^^ . _:b558136636 . _:b558137685 . _:b558136637 . _:b558137449 . . _:b558136638 . _:b558136639 . _:b558138134 "2"^^ . . _:b558136632 . _:b558136633 . _:b558137448 . . _:b558136634 . _:b558136635 . _:b558138129 "2"^^ . . _:b558136628 . _:b558136629 . _:b558137451 . _:b558136630 . _:b558137343 . _:b558137302 . _:b558136631 . _:b558138128 "2"^^ . _:b558136624 . _:b558136625 . _:b558137450 . . _:b558136626 . _:b558136627 . _:b558138131 "2"^^ . _:b558136620 . _:b558136621 . _:b558137461 . _:b558136622 . _:b558137243 . _:b558136623 . _:b558138130 "2"^^ . _:b558136616 . _:b558136617 . _:b558137460 . . _:b558137222 . _:b558136618 . _:b558136619 . _:b558138141 "2"^^ . _:b558136612 . . _:b558137600 . _:b558137463 . _:b558136613 . _:b558136387 . _:b558136614 . _:b558136615 . _:b558138140 "2"^^ . _:b558136608 . _:b558136609 . _:b558137462 . _:b558136610 . _:b558136611 . _:b558138143 "2"^^ . _:b558137052 . _:b558137053 . _:b558137457 . _:b558137054 . _:b558137055 . _:b558138142 "2"^^ . _:b558137048 . . _:b558137456 . _:b558137049 . . . _:b558137050 . _:b558137051 . _:b558138137 "2"^^ . . _:b558137044 . _:b558137045 . _:b558137459 . _:b558137046 . _:b558137047 . _:b558138136 "2"^^ . _:b558136280 . _:b558137040 . _:b558137041 . _:b558137458 . _:b558137042 . _:b558137043 . _:b558138139 "2"^^ . _:b558137036 . _:b558137006 . . _:b558137469 . _:b558137037 . _:b558137038 . _:b558137039 . _:b558138138 "2"^^ . _:b558137032 . _:b558137033 . _:b558137468 . _:b558137034 . _:b558136795 . _:b558138149 "2"^^ . . _:b558137035 . _:b558137028 . _:b558137029 . _:b558137471 . _:b558137030 . _:b558137031 . _:b558138148 "2"^^ . _:b558137024 . _:b558137025 . _:b558137470 . _:b558137026 . . _:b558137027 . _:b558138151 "2"^^ . _:b558137084 . _:b558137085 . _:b558137465 . _:b558137206 . _:b558137086 . _:b558137087 . _:b558138150 "2"^^ . _:b558137080 . _:b558137081 . _:b558137464 . _:b558137082 . _:b558137083 . _:b558138145 "2"^^ . . _:b33179846 "This model has also been supported by bulk sequencing data in prostate cancer>>29<< and in rearrangement patterns called firestorms30 or chromothripsis31." . _:b558137076 . _:b558137077 . _:b558137467 . _:b558137078 . _:b558137079 . _:b558138144 "2"^^ . _:b558137072 . _:b558137292 . _:b558137073 . _:b558137964 . _:b558137466 . _:b558137074 . _:b558137075 . _:b558138147 "2"^^ . _:b558137068 . _:b558137069 . _:b558137477 . _:b558137070 . _:b558137071 . _:b558138146 "2"^^ . _:b558137064 . _:b558137065 . _:b558137476 . _:b558137066 . _:b558137570 . _:b558137067 . _:b558138157 "2"^^ . _:b558137913 . _:b558137060 . _:b558137256 . . _:b558137479 . _:b558137061 . _:b558137062 . _:b558137063 . _:b558138156 "2"^^ . _:b558137056 . _:b558137057 . _:b558137478 . _:b558137058 . _:b558136545 . _:b558138159 "2"^^ . _:b558137059 . _:b558136988 . _:b558138119 . _:b558137477 . _:b558136989 . _:b558137473 . _:b558136990 . . _:b558138158 "2"^^ . _:b558136991 . _:b558136984 . _:b558136985 . _:b558137472 . . _:b558136986 . . _:b558136987 . _:b558138153 "2"^^ . _:b558136980 . _:b558136981 . _:b558137475 . _:b558136982 . _:b558137627 . _:b558136983 . _:b558138152 "2"^^ . _:b558136976 . _:b558136977 . _:b558137474 . _:b558136978 . _:b558136979 . _:b558138155 "2"^^ . _:b558136972 . . _:b558137485 . _:b558136973 . _:b558136974 . . _:b558138154 "2"^^ . _:b558136975 . _:b558136968 . _:b558136969 . _:b558137484 . _:b558136970 . . _:b558138165 "2"^^ . _:b558136971 . _:b558136964 . _:b558136965 . _:b558137487 . _:b558136852 . _:b558136966 . _:b558136967 . _:b558138164 "2"^^ . . _:b558136960 . _:b558136961 . _:b558137486 . _:b558136962 . . _:b558138167 "2"^^ . _:b558136983 . _:b558136963 . _:b558137020 . _:b558137021 . _:b558137481 . . _:b558137022 . _:b558137023 . _:b558138166 "2"^^ . _:b558137016 . _:b558137017 . _:b558137480 . _:b558137018 . _:b558137019 . _:b558138161 "2"^^ . _:b558137012 . _:b558137013 . _:b558137483 . _:b558137014 . _:b558137015 . _:b558138160 "2"^^ . _:b558137008 . _:b558137009 . _:b558137482 . . _:b558137010 . _:b558136658 . _:b558138163 "2"^^ . _:b558137011 . _:b558137004 . _:b558137005 . _:b558137493 . _:b558136323 . _:b558137006 . _:b558137007 . _:b558138162 "2"^^ . . _:b558137000 . _:b558137001 . _:b558137492 . _:b558137002 . _:b558137003 . _:b558137715 . _:b558136996 . _:b558138074 . _:b558136997 . _:b558137495 . _:b558137086 . _:b558136998 . _:b558136999 . _:b558136771 . _:b558137465 . _:b558136992 . _:b558136993 . _:b558137494 . _:b558136994 . _:b558137767 . _:b558136995 . _:b558136924 . _:b558136925 . _:b558137489 . . _:b558138138 . _:b558136926 . _:b558136927 . _:b558137525 . _:b558136920 . . _:b558137488 . _:b558136921 . _:b558136922 . _:b558137941 . _:b558136923 . _:b558136916 . _:b558136917 . _:b558137491 . _:b558136918 . _:b558136440 . _:b558136661 . _:b558136919 . _:b558136912 . _:b558136913 . _:b558137490 . _:b558136914 . _:b558136915 . _:b558136908 . _:b558137082 . _:b558136909 . _:b558137501 . . _:b558136910 . _:b558136822 . _:b558136911 . _:b558136904 . . _:b558137500 . _:b558136905 . . _:b558136906 . . _:b558136907 . _:b558136900 . _:b558136901 . _:b558137503 . _:b558137142 . _:b558136902 . _:b558136903 . _:b558136896 . _:b558136897 . _:b558137502 . _:b558137483 . . _:b558136898 . _:b558136899 . _:b558136956 . _:b558137322 . _:b558136343 . _:b558137497 . _:b558136957 . _:b558136958 . _:b558136959 . . _:b558136952 . _:b558136953 . _:b558137496 . _:b558136954 . _:b558136955 . _:b558136948 . _:b558136949 . _:b558137499 . _:b558136950 . _:b558136951 . _:b558136944 . _:b558136945 . _:b558137498 . _:b558136274 . _:b558136946 . _:b558137635 . _:b558136947 . _:b558136940 . _:b558136941 . _:b558137509 . _:b558136942 . _:b558136943 . _:b558136936 . _:b558137028 . _:b558136937 . _:b558137508 . _:b558136938 . _:b558136939 . _:b558136932 . _:b558136933 . _:b558137511 . _:b558136934 . _:b558137744 . _:b558136935 . . _:b558136928 . _:b558136929 . _:b558137510 . _:b558136930 . _:b558136931 . _:b558136860 . _:b558136861 . _:b558137505 . _:b558136862 . _:b558136863 . _:b558136856 . _:b558136857 . _:b558137504 . _:b558137429 . _:b558136858 . _:b558136859 . _:b33179850 "A punctuated model is consistent with the mechanisms that underlie CNAs, including chromosome missegregation32, cytokinesis defects and breakage-fusion-bridge>>33<<, which can generate complex rearrangements in just a few cell divisions." . _:b558136852 . _:b558137482 . _:b558136853 . _:b558137507 . _:b558136854 . _:b558136876 . _:b558136855 . . _:b558136848 . _:b558136849 . _:b558138096 . _:b558137506 . _:b558136850 . _:b558136851 . _:b558136844 . _:b558136845 . _:b558137517 . . _:b558136846 . _:b558136847 . _:b558136840 . _:b558136890 . _:b558137516 . _:b558136841 . _:b558136842 . _:b558136843 . _:b558136302 . _:b558136836 . . _:b558137519 . _:b558136837 . . _:b558136838 . _:b558136839 . . _:b558136832 . _:b558136833 . _:b558137518 . _:b558136834 . _:b558136835 . _:b558136750 . _:b558136892 . _:b558136893 . _:b558137540 . _:b558137513 . _:b558136894 . _:b558136895 . _:b558136888 . _:b558137861 . _:b558136889 . _:b558137512 . _:b558136908 . _:b558136890 . _:b558136891 . _:b558136884 . _:b558136885 . _:b33179871 "We also achieved low false positive error rates for point mutations (FPR = 1.24e-6), equivalent to 1\u20132 errors per million bases, which represents a major technical improvement over previous methods (FPR= 2.52e-5 and 4e-5)>>14<<,19." . _:b558137515 . _:b558136886 . _:b558136887 . _:b558136880 . _:b558136375 . _:b558137514 . _:b558136881 . _:b558136882 . _:b558138098 . _:b558136883 . _:b558137866 . _:b558136876 . _:b558136877 . _:b558137525 . _:b558136878 . _:b558136879 . _:b558136872 . . _:b558137524 . _:b558136873 . _:b558136874 . _:b558136875 . _:b558136868 . _:b558136869 . _:b558137527 . _:b558136870 . _:b558136871 . _:b558136864 . . _:b558137526 . _:b558136865 . _:b558136866 . _:b558136867 . _:b558137308 . _:b558137309 . _:b558137521 . _:b558137310 . _:b558137311 . _:b558136789 . . _:b558137304 . _:b558137365 . _:b558137305 . _:b558137520 . . _:b558137306 . _:b558137307 . _:b558137443 . _:b558137300 . _:b558137301 . _:b558137523 . _:b558136449 . _:b558137302 . _:b558137303 . _:b558137296 . _:b558137297 . _:b558137522 . . _:b558137298 . _:b558137299 . _:b558137292 . _:b558137293 . _:b558137533 . _:b558136749 . _:b558138110 . _:b558137294 . _:b558137295 . . _:b558137288 . . _:b558137532 . _:b558137289 . _:b558137290 . _:b558137291 . . . _:b558137284 . _:b558137285 . _:b558137535 . _:b558137286 . _:b558137287 . _:b558136997 . _:b558137280 . . _:b558137281 . _:b558137534 . _:b558137282 . _:b558137283 . _:b558137340 . _:b558137341 . _:b558137529 . _:b558137342 . _:b558137343 . _:b558137336 . _:b558137337 . _:b558137528 . _:b558137338 . _:b558137339 . _:b558137332 . _:b558137333 . _:b558137531 . . _:b558137334 . _:b558137335 . _:b558137328 . _:b558137329 . _:b558137530 . _:b558137330 . _:b558137331 . _:b558137324 . _:b558137325 . _:b558137541 . _:b558136888 . _:b558137326 . _:b558137327 . _:b558137320 . _:b558137321 . _:b558137540 . . _:b558137322 . . _:b558137323 . _:b558137316 . _:b558137317 . _:b558137543 . _:b558137318 . . _:b558137319 . . _:b558137312 . . _:b558137542 . _:b558136268 . _:b558137313 . _:b558137314 . _:b558137315 . . _:b558137244 . . . _:b558137537 . _:b558137245 . _:b558137246 . _:b558137247 . _:b558137240 . _:b558137241 . _:b558137536 . _:b558136558 . _:b558137242 . _:b558137243 . _:b558137008 . _:b558137236 . _:b558137237 . _:b558137539 . _:b558137238 . _:b558137239 . _:b558137232 . _:b558137233 . _:b558137538 . _:b558137234 . _:b558137235 . _:b558137228 . . _:b558137549 . _:b558137229 . _:b558137230 . _:b558137231 . _:b558137224 . _:b558137225 . _:b558137548 . _:b558137226 . _:b558138152 . _:b558137227 . _:b558137220 . . _:b558137221 . _:b558137551 . _:b558137222 . . _:b558137223 . _:b558137216 . _:b558137217 . _:b558137550 . _:b558137218 . _:b558137219 . _:b558137276 . _:b558137277 . _:b558137910 . _:b558137545 . _:b558137278 . _:b558137279 . _:b558137272 . . _:b558137544 . _:b558137273 . _:b558137274 . _:b558137275 . _:b558137268 . _:b558137269 . _:b558137547 . _:b558137270 . _:b558137271 . _:b558137264 . _:b558137265 . _:b558137546 . _:b558137266 . _:b558137793 . . _:b558137267 . _:b558137260 . _:b558137261 . _:b558137557 . _:b558137262 . _:b558137263 . _:b558137256 . _:b558137257 . _:b558137556 . _:b558137258 . _:b558137290 . _:b558137259 . _:b558137252 . . _:b558137559 . _:b558137253 . _:b558137254 . _:b558137255 . _:b558137248 . _:b558137249 . _:b558137558 . _:b558136856 . _:b558136347 . _:b558137250 . _:b558137251 . _:b558137237 . _:b558137180 . _:b558137181 . _:b558137553 . _:b558136697 . _:b558137182 . _:b558137183 . _:b558137176 . _:b558137177 . _:b558137552 . _:b558137178 . _:b558138148 . _:b558137179 . _:b558137172 . _:b558137173 . _:b558137555 . _:b558137174 . _:b558137175 . _:b558137168 . _:b558137169 . _:b558137554 . . _:b558137170 . _:b558137171 . _:b558137164 . _:b558137165 . _:b558137565 . . _:b558137166 . _:b558137167 . _:b558137160 . _:b558137161 . _:b558137564 . . _:b558137162 . _:b558137163 . _:b558137156 . _:b558137157 . _:b558137567 . _:b558137158 . . _:b558137159 . . _:b558137152 . _:b558137153 . _:b558137566 . . _:b558137154 . . _:b558137155 . _:b558137212 . _:b558137213 . _:b558137561 . _:b558137328 . _:b558137214 . _:b558136886 . _:b558137215 . _:b558137208 . _:b558137209 . _:b558137560 . . _:b558137210 . _:b558136385 . _:b558137211 . _:b558137204 . _:b558137104 . _:b558137205 . _:b558138108 . _:b558137563 . _:b558137206 . _:b558137207 . _:b558137200 . _:b558137201 . _:b558137562 . . _:b558137202 . _:b558137203 . _:b558137196 . _:b558137026 . _:b558137197 . _:b558137573 . _:b558137198 . _:b558137388 . _:b558137199 . _:b558137192 . _:b558137193 . _:b558137703 . _:b558137572 . _:b558137194 . _:b558137195 . _:b558137712 . _:b558137188 . _:b558137189 . _:b558137575 . _:b558137190 . . _:b558137191 . _:b558137184 . _:b558137185 . _:b558137574 . _:b558137186 . _:b558137187 . _:b558136388 . _:b558136952 . _:b558137116 . . _:b558137569 . _:b558137116 . _:b558137117 . _:b558137118 . _:b558137119 . _:b558137112 . _:b558137646 . _:b558137113 . _:b558137568 . . . _:b558137114 . _:b558137115 . _:b558137108 . _:b558137109 . _:b558137571 . _:b558137110 . _:b558137852 . . _:b558137111 . . _:b558137104 . _:b558137105 . _:b558137570 . _:b558137106 . _:b558137107 . _:b558137100 . _:b558137101 . _:b558137581 . _:b558137102 . _:b558137103 . _:b558137096 . _:b558137097 . _:b558137580 . _:b558137098 . _:b558137099 . _:b558137092 . _:b558137093 . _:b558137583 . _:b558137094 . _:b558137095 . _:b33179851 . . _:b558137088 . . _:b558137582 . _:b558137089 . . _:b558137090 . _:b558137091 . _:b558136328 . _:b558137148 . . _:b558137577 . . _:b558137149 . _:b558137150 . _:b558137986 . _:b558137151 . _:b558137479 . _:b558137144 . . _:b558137576 . _:b558137145 . . _:b558137146 . . _:b558137147 . . _:b558137140 . . _:b558136641 . _:b558137579 . _:b558137141 . _:b558137142 . _:b558137774 . _:b558137143 . _:b33179855 . _:b558137136 . _:b558137137 . _:b558137578 . _:b558137138 . _:b558137139 . _:b558137505 . . _:b558137132 . _:b558137133 . _:b558137589 . _:b558137134 . _:b558137135 . _:b558136657 . _:b558137128 . _:b558137129 . _:b558137588 . _:b558137130 . . . _:b558137131 . _:b558137124 . _:b558137125 . _:b558137898 . _:b558137591 . _:b558137126 . . _:b558137308 . _:b558137127 . . _:b558137120 . _:b558137121 . _:b558137590 . _:b558136916 . _:b558137122 . . _:b558137123 . _:b558137480 . _:b558137213 . _:b558137585 . _:b558137584 . _:b558137587 . . _:b558137586 . _:b558137597 . _:b558136807 . . _:b558138151 . _:b558137596 . _:b558137599 . . _:b558137598 . . _:b558138040 . . _:b558137108 . _:b558137593 . _:b558137743 . . _:b558137592 . . . _:b558137595 . _:b558137574 . . _:b558136991 . _:b558137594 . _:b558136365 . . . . . . . . _:b558136966 . _:b558136933 . _:b558137776 . _:b558137934 . _:b558138161 . _:b558137946 . _:b558137287 . . . . _:b558137824 . . _:b558136653 . . _:b558136393 . . . _:b558137541 . _:b558136974 . _:b558136481 . . _:b558136397 . _:b558137554 . . . . . . _:b558136554 . . _:b558137378 . _:b558137837 . _:b558137963 . _:b558138026 . . . . _:b558137891 . _:b558136715 . _:b558136998 . _:b558136684 . _:b558137512 . _:b558136386 . _:b558137136 . . _:b558136727 . _:b558136875 . _:b558136475 . . . . _:b558137341 . _:b558136345 . . . . _:b558136968 . _:b558137830 . . _:b558137724 . . . _:b558137990 . . . . _:b558137171 . . _:b558136954 . . . . _:b558137865 . _:b558136547 . . _:b558136874 . _:b558136765 . _:b558137019 . _:b558137110 . . . _:b33179845 _:b33179856 . _:b33179845 _:b33179857 . _:b558137079 . _:b558137281 . _:b558137555 . . _:b558137697 . _:b558137772 . _:b558138038 . . _:b558137148 . _:b33179845 _:b33179846 . _:b33179845 _:b33179847 . . _:b33179845 _:b33179848 . . _:b33179845 _:b33179849 . _:b33179845 _:b33179850 . _:b33179845 _:b33179851 . . _:b33179845 _:b33179852 . _:b33179845 _:b33179853 . _:b558137842 . . _:b33179845 _:b33179854 . . _:b33179845 _:b33179855 . _:b33179885 . _:b558137777 . . . _:b558137022 . _:b558137587 . . _:b558136567 . _:b558137403 . . . . _:b558137841 . . _:b33179864 _:b33179868 . _:b33179864 _:b33179869 . _:b33179864 _:b33179870 . _:b33179864 _:b33179871 . _:b33179864 _:b33179865 . _:b33179864 _:b33179866 . _:b33179864 _:b33179867 . . . _:b33179864 _:b33179872 . _:b558136827 . _:b558136708 . . _:b558136731 . . _:b33179858 _:b33179860 . _:b558137616 . _:b33179858 _:b33179861 . _:b33179858 _:b33179862 . . _:b33179858 _:b33179863 . . _:b558138004 . _:b33179858 _:b33179859 . . . _:b558136927 . _:b33179873 _:b33179874 . _:b33179873 _:b33179875 . _:b33179873 _:b33179876 . _:b558137951 . . . . _:b558137588 . _:b558137249 . _:b33179877 _:b33179878 . _:b33179877 _:b33179879 . . _:b558138017 . _:b33179877 _:b33179880 . _:b558137764 . . _:b558137031 . _:b558137524 . _:b33179883 _:b33179884 . _:b558136469 . _:b33179883 _:b33179885 . _:b558136391 . _:b558137349 "2"^^ . . _:b33179881 _:b33179882 . . _:b558137348 "2"^^ . _:b558137351 "2"^^ . . . _:b558136913 . _:b558137350 "2"^^ . . _:b558137567 . _:b558137345 "2"^^ . _:b558136313 . _:b558137632 . _:b558137344 "2"^^ . _:b558137617 . . _:b558137347 "2"^^ . _:b558136926 . _:b558137346 "2"^^ . _:b558137357 "2"^^ . . _:b558137356 "2"^^ . _:b33179872 "We also achieved low false positive error rates for point mutations (FPR = 1.24e-6), equivalent to 1\u20132 errors per million bases, which represents a major technical improvement over previous methods (FPR= 2.52e-5 and 4e-5)14,>>19<<." . _:b558136583 . . _:b558137359 "2"^^ . _:b558137337 . _:b558137217 . _:b558137358 "2"^^ . _:b558137353 "2"^^ . . . . _:b558137352 "2"^^ . _:b558137355 "2"^^ . . _:b558137354 "2"^^ . . . _:b558137365 "2"^^ . _:b558136896 . . _:b558138034 . . _:b558136490 . . _:b558137364 "2"^^ . _:b558137367 "2"^^ . _:b558137366 "2"^^ . . . . . . _:b558137361 "2"^^ . _:b558137360 "2"^^ . . _:b558136964 . . _:b558137363 "2"^^ . _:b558136468 . . _:b558137362 "2"^^ . _:b558136330 . . _:b558137373 "2"^^ . _:b558137372 "2"^^ . . . _:b558137375 "2"^^ . . _:b558137711 . . _:b558137374 "2"^^ . _:b558137267 . _:b558137369 "2"^^ . . . _:b558137368 "2"^^ . _:b558137371 "2"^^ . . . . . _:b558137370 "2"^^ . _:b558137381 "2"^^ . _:b558137380 "2"^^ . . _:b558137383 "2"^^ . . _:b558136711 . _:b558137382 "2"^^ . _:b558137916 . _:b558137377 "2"^^ . . . _:b558137376 "2"^^ . _:b558137313 . . _:b558137379 "2"^^ . _:b558137785 . . _:b558137378 "2"^^ . . _:b558136445 . _:b558137389 "2"^^ . . _:b558137388 "2"^^ . _:b558136269 . . _:b558137391 "2"^^ . . _:b558136500 . _:b558137390 "2"^^ . . _:b558137971 . _:b558137385 "2"^^ . _:b558137556 . _:b558137387 . _:b558136873 . _:b558138049 . _:b558137384 "2"^^ . _:b558136935 . _:b558137696 . _:b558137387 "2"^^ . _:b558138145 . _:b558137386 "2"^^ . _:b558136810 . . _:b558137397 "2"^^ . _:b558137396 "2"^^ . _:b558138123 . _:b558138093 . . _:b558137399 "2"^^ . _:b558137481 . _:b558137398 "2"^^ . _:b558137713 . . _:b558137393 "2"^^ . . . . . _:b558137392 "2"^^ . _:b558137395 "2"^^ . _:b558137770 . _:b558137914 . . . _:b558137394 "2"^^ . _:b558137405 "2"^^ . _:b558137537 . . _:b558137404 "2"^^ . . _:b558137662 . _:b558137407 "2"^^ . _:b558137523 . _:b558137595 . _:b558137406 "2"^^ . _:b558137052 . _:b558137401 "2"^^ . _:b558136467 . _:b558137400 "2"^^ . _:b558137403 "2"^^ . _:b558137402 "2"^^ . . _:b558137413 "2"^^ . . _:b558137412 "2"^^ . . _:b558136314 . _:b558136681 . . _:b558137415 "2"^^ . _:b558137414 "2"^^ . _:b558138008 . . _:b558137351 . _:b558137409 "2"^^ . _:b558137424 . _:b558137408 "2"^^ . _:b558137134 . . _:b558137411 "2"^^ . . _:b558137410 "2"^^ . _:b558137421 "2"^^ . _:b558137420 "2"^^ . _:b558137569 . _:b558137423 "2"^^ . _:b558137016 . _:b558137422 "2"^^ . _:b558137833 . _:b558137417 "2"^^ . _:b558136287 . _:b558136758 . _:b558137416 "2"^^ . . _:b558137467 . _:b558137304 . _:b558137419 "2"^^ . _:b558137418 "2"^^ . _:b558136741 . _:b558137429 "2"^^ . _:b558137729 . _:b558136523 . _:b558137428 "2"^^ . . _:b558137968 . . . _:b558137431 "2"^^ . . . _:b558138061 . _:b558137430 "2"^^ . _:b558136382 . . _:b558136357 . . _:b558137425 "2"^^ . _:b558137424 "2"^^ . _:b558137427 "2"^^ . _:b558137426 "2"^^ . _:b558136364 . . _:b558137437 "2"^^ . _:b558137928 . _:b558136342 . _:b558137436 "2"^^ . . . . _:b558137439 "2"^^ . _:b558137438 "2"^^ . . _:b558137433 "2"^^ . . _:b558137432 "2"^^ . _:b558137155 . . _:b558137435 "2"^^ . _:b558136726 . _:b558137434 "2"^^ . . _:b558137445 "2"^^ . . . _:b558137444 "2"^^ . _:b558137943 . _:b558136931 . . _:b558137447 "2"^^ . _:b33179881 "single-molecule targeted deep sequencing" . . . _:b558137446 "2"^^ . . _:b558136362 . . _:b558137441 "2"^^ . . _:b558137440 "2"^^ . _:b558136994 . . _:b558136769 . _:b558137443 "2"^^ . _:b558136332 . _:b558137442 "2"^^ . _:b558137453 "2"^^ . _:b558136575 . _:b558137452 "2"^^ . _:b558136694 . _:b558136373 . _:b558137455 "2"^^ . . _:b558137800 . . _:b558137454 "2"^^ . _:b558137118 . . _:b558137449 "2"^^ . . _:b558137448 "2"^^ . _:b558137221 . _:b558136534 . . _:b558137451 "2"^^ . _:b558136507 . _:b558137450 "2"^^ . . _:b558137863 . _:b558137461 "2"^^ . _:b558137460 "2"^^ . _:b558138043 . _:b558137463 "2"^^ . . _:b558137462 "2"^^ . . _:b558136451 . _:b558137457 "2"^^ . . . _:b558137456 "2"^^ . . . _:b558138081 . _:b558137681 . _:b558137459 "2"^^ . . . _:b558137458 "2"^^ . . _:b558137469 "2"^^ . . _:b558137468 "2"^^ . _:b558138058 . _:b558136773 . _:b558137370 . . _:b558137471 "2"^^ . . _:b558137787 . _:b558137470 "2"^^ . _:b558137465 "2"^^ . _:b558137464 "2"^^ . . _:b558137074 . _:b558137467 "2"^^ . _:b558137297 . _:b558136379 . _:b558137999 . _:b558137466 "2"^^ . . _:b558137477 "2"^^ . _:b558137476 "2"^^ . . _:b558137479 "2"^^ . . _:b558136979 . _:b558137478 "2"^^ . _:b558137875 . . _:b558137410 . _:b558137325 . _:b558137473 "2"^^ . _:b558136757 . _:b558137472 "2"^^ . _:b558137475 "2"^^ . _:b558137474 "2"^^ . _:b558136651 . . _:b558137485 "2"^^ . . _:b558137484 "2"^^ . . . _:b558137487 "2"^^ . _:b558137949 . . _:b558136579 . . _:b558137486 "2"^^ . . _:b33179846 . _:b558137481 "2"^^ . _:b558137480 "2"^^ . . _:b558136786 . _:b558136312 . _:b558137483 "2"^^ . _:b558137482 "2"^^ . _:b558137996 . _:b558137493 "2"^^ . _:b558136839 . _:b558137492 "2"^^ . . _:b558137495 "2"^^ . _:b558137494 "2"^^ . _:b558137296 . _:b558137489 "2"^^ . _:b558137488 "2"^^ . . _:b558137491 "2"^^ . _:b558136878 . _:b558136709 . _:b558137490 "2"^^ . _:b558136318 . . _:b558137501 "2"^^ . _:b558137498 . _:b558137872 . _:b558137500 "2"^^ . . . . _:b558137503 "2"^^ . _:b558137502 "2"^^ . . _:b558137606 . _:b558137497 "2"^^ . _:b558136520 . . . _:b558137496 "2"^^ . . _:b558137499 "2"^^ . _:b558136975 . _:b558136818 . . _:b558137498 "2"^^ . _:b558137509 "2"^^ . _:b558137508 "2"^^ . . _:b558136650 . _:b558137511 "2"^^ . _:b558137081 . . _:b558137510 "2"^^ . _:b558137172 . _:b558137505 "2"^^ . . _:b558137504 "2"^^ . _:b558137507 "2"^^ . . . _:b558137893 . . . _:b558137506 "2"^^ . _:b558136762 . _:b558136712 . _:b558137517 "2"^^ . _:b558137516 "2"^^ . . _:b558137519 "2"^^ . . _:b558137518 "2"^^ . . _:b558137513 "2"^^ . _:b33179861 . _:b558137512 "2"^^ . . . _:b558137515 "2"^^ . _:b558137350 . _:b558137284 . _:b558137994 . _:b558137514 "2"^^ . _:b558137901 . _:b558137486 . _:b558137525 "2"^^ . _:b558137796 . _:b558136522 . _:b558137524 "2"^^ . _:b33179870 . _:b558136303 . _:b558137037 . _:b558137761 . _:b558137527 "2"^^ . _:b33179871 . . _:b558137526 "2"^^ . _:b558136324 . _:b558137327 . . _:b558137521 "2"^^ . _:b558137520 "2"^^ . . _:b558137523 "2"^^ . _:b558137522 "2"^^ . . _:b558137346 . _:b558137533 "2"^^ . . . . _:b558136880 . _:b558137532 "2"^^ . _:b558137535 "2"^^ . _:b558137534 "2"^^ . . . _:b558137858 . . _:b558137529 "2"^^ . _:b558137528 "2"^^ . . . _:b558137531 "2"^^ . _:b558137530 "2"^^ . _:b558138063 . _:b558137577 . _:b558136672 . . _:b558137189 . . _:b558137541 "2"^^ . . _:b558137540 "2"^^ . _:b558137012 . _:b558136914 . _:b558137141 . _:b558137543 "2"^^ . . _:b558138107 . _:b558137542 "2"^^ . . . _:b558137537 "2"^^ . _:b558136627 . _:b558137288 . _:b558137536 "2"^^ . _:b558136528 . . . _:b33179853 "These rare mutations may play an important role in diversifying the phenotypes of cancer cells, allowing them to surive selective pressures in the tumor microenvironment, including the immune system, hypoxia and chemotherapy35,>>36<<." . _:b558137539 "2"^^ . _:b558137348 . . _:b558136845 . _:b558137538 "2"^^ . _:b558137549 "2"^^ . _:b558137805 . . _:b558136978 . _:b558137548 "2"^^ . . _:b558136793 . _:b558137551 "2"^^ . . _:b558137550 "2"^^ . . _:b558137298 . _:b558137832 . _:b558137545 "2"^^ . _:b558137769 . _:b558138159 . _:b558136497 . . _:b558137544 "2"^^ . _:b558136989 . _:b558138114 . _:b558137547 "2"^^ . _:b558137546 "2"^^ . _:b558137557 "2"^^ . _:b558137306 . _:b558137556 "2"^^ . _:b558138091 . _:b558137033 . _:b558138116 . _:b558137559 "2"^^ . _:b558136255 . _:b558137558 "2"^^ . _:b558137553 "2"^^ . . _:b558137169 . _:b558136938 . _:b558137552 "2"^^ . _:b558136837 . _:b558137944 . _:b558137555 "2"^^ . _:b558137554 "2"^^ . _:b558137565 "2"^^ . _:b558138162 . _:b558137157 . . _:b558136739 . _:b558137564 "2"^^ . _:b558137784 . _:b558137567 "2"^^ . _:b558137741 . _:b558138030 . . _:b558137566 "2"^^ . _:b558137295 . _:b558137529 . . _:b558137561 "2"^^ . _:b558136767 . _:b558137655 . . _:b558137628 . _:b558137560 "2"^^ . _:b558137956 . _:b558137563 "2"^^ . _:b558136648 . . _:b558137562 "2"^^ . _:b558137573 "2"^^ . _:b558136847 . . _:b558137572 "2"^^ . _:b558137647 . _:b558137575 "2"^^ . _:b558137574 "2"^^ . . . _:b558137569 "2"^^ . . _:b558136570 . . _:b558137568 "2"^^ . . . _:b558137571 "2"^^ . . . _:b558137570 "2"^^ . _:b558137581 "2"^^ . _:b558136483 . . . _:b558137580 "2"^^ . . _:b558137583 "2"^^ . . . . _:b558137582 "2"^^ . _:b558136493 . _:b558136644 . _:b558137577 "2"^^ . _:b558137896 . . _:b558137576 "2"^^ . . . _:b558137773 . _:b558137579 "2"^^ . _:b558137578 "2"^^ . _:b558136816 . _:b558137589 "2"^^ . . _:b558137588 "2"^^ . _:b558138097 . _:b558137591 . . _:b558137591 "2"^^ . _:b558137121 . _:b558136638 . _:b558137590 "2"^^ . _:b558137723 . _:b558137442 . _:b558136485 . _:b558137585 "2"^^ . _:b558136868 . _:b558138066 . _:b558137009 . _:b558136569 . _:b558137584 "2"^^ . _:b558137587 "2"^^ . . _:b558137586 "2"^^ . _:b558137597 "2"^^ . . . _:b558136655 . _:b558137596 "2"^^ . _:b558136603 . _:b558137599 "2"^^ . . _:b558137598 "2"^^ . . _:b558137593 "2"^^ . . _:b558137592 "2"^^ . _:b558136819 . . _:b558137595 "2"^^ . _:b558136320 . . _:b558136788 . _:b558136374 . _:b558138018 . _:b558137594 "2"^^ . . _:b558136911 . _:b558137605 "2"^^ . _:b558136546 . _:b558137604 "2"^^ . _:b558137699 . . _:b558137848 . _:b558137607 "2"^^ . "10.1038%2Fnature13600" . _:b558137606 "2"^^ . _:b558138005 . . _:b558137818 . . _:b558137601 "2"^^ . _:b558137358 . . _:b558138033 . _:b558137664 . _:b558136435 . _:b558137600 "2"^^ . _:b558136247 . . _:b558137360 . . _:b558137603 "2"^^ . _:b558137414 . _:b558136814 . _:b558137294 . _:b558136466 . _:b558137602 "2"^^ . _:b558138007 . _:b558136680 . . . _:b558137054 . _:b558137613 "2"^^ . _:b558136817 . _:b558137629 . _:b558137612 "2"^^ . _:b33179852 . _:b558137392 . "PMC0" . _:b558137615 "2"^^ . . _:b558136755 . _:b558137614 "2"^^ . . . _:b558136340 . _:b558136823 . _:b558137609 "2"^^ . _:b558137608 "2"^^ . . _:b558136752 . _:b558137611 "2"^^ . _:b558137807 . _:b558136259 . _:b558137610 "2"^^ . . . _:b558137621 "2"^^ . . _:b558137620 "2"^^ . _:b558136338 . _:b558137835 . _:b558136971 . _:b558137623 "2"^^ . . _:b558137190 . _:b558136413 . _:b558137622 "2"^^ . _:b558137617 "2"^^ . _:b558137355 . _:b558137616 "2"^^ . _:b558137966 . . . _:b558137619 "2"^^ . _:b558137207 . _:b558137618 "2"^^ . _:b558136867 . . _:b558137629 "2"^^ . _:b558137321 . _:b558137061 . _:b558137641 . _:b558136582 . _:b558137628 "2"^^ . . . _:b558137631 "2"^^ . . . . _:b558137630 "2"^^ . . . _:b558137625 "2"^^ . _:b558137675 . _:b558137624 "2"^^ . . _:b558136566 . . _:b558137627 "2"^^ . _:b558136904 . . _:b558137626 "2"^^ . _:b558137568 . . _:b558137637 "2"^^ . _:b558138137 . _:b558137636 "2"^^ . _:b558136864 . _:b33179845 . . _:b558137639 "2"^^ . . . . _:b558137638 "2"^^ . _:b558137633 "2"^^ . _:b33179864 . . . _:b558137632 "2"^^ . . _:b558137635 "2"^^ . . . _:b558136560 . _:b33179858 . _:b558137634 "2"^^ . _:b558138048 . . . _:b558137645 "2"^^ . _:b33179881 . _:b558137644 "2"^^ . . _:b33179883 . _:b33179877 . _:b558136894 . _:b558137647 "2"^^ . . _:b33179873 . _:b558137646 "2"^^ . . . _:b558137641 "2"^^ . . _:b558137640 "2"^^ . _:b558137643 "2"^^ . _:b558138078 . _:b558137985 . _:b558137642 "2"^^ . . . _:b558137653 "2"^^ . _:b558136872 . _:b558137398 . . _:b558137652 "2"^^ . . . _:b33179878 "Many of these mutations were previously reported in the TCGA breast cancer cohort>>7<<. Pathway analysis revealed two major pathways that were disrupted during tumor evolution: TGF\u03B2 (p=9.9e-2) and extracellular matrix-receptor signaling (p=2.7e-2). Copy number profiling identified many chromosomal deletions, in addition to" . _:b558137655 "2"^^ . . _:b558137980 . . _:b558137654 "2"^^ . _:b558137468 . _:b558137649 "2"^^ . _:b558136406 . _:b558136613 . _:b558137648 "2"^^ . _:b558137651 "2"^^ . _:b558137542 . _:b558136589 . _:b558136628 . _:b558137650 "2"^^ . . _:b558137661 "2"^^ . . _:b558137660 "2"^^ . _:b558137097 . _:b558137663 "2"^^ . . _:b558137667 . _:b558137791 . . _:b558137662 "2"^^ . _:b558136317 . . _:b558137657 "2"^^ . . . _:b558137251 . _:b558137656 "2"^^ . _:b558137659 "2"^^ . . . _:b558137658 "2"^^ . _:b558137585 . . . . _:b558137669 "2"^^ . _:b558137668 "2"^^ . . _:b558137615 . _:b558137671 "2"^^ . _:b33179862 . _:b558137083 . _:b558137670 "2"^^ . _:b558137665 "2"^^ . _:b558137664 "2"^^ . . _:b558137412 . _:b558137667 "2"^^ . _:b558137950 . . _:b558137666 "2"^^ . _:b558138019 . . _:b558137677 "2"^^ . _:b558137676 "2"^^ . . _:b558136949 . . _:b558137679 "2"^^ . . . _:b558137678 "2"^^ . . _:b558137673 "2"^^ . . _:b558137672 "2"^^ . _:b558137315 . _:b558136509 . _:b558137919 . _:b558137675 "2"^^ . . _:b558137674 "2"^^ . . _:b558137685 "2"^^ . _:b558137183 . . _:b558136824 . _:b558137684 "2"^^ . _:b558136289 . _:b558137687 "2"^^ . _:b558137686 "2"^^ . _:b558137681 "2"^^ . _:b558137680 "2"^^ . _:b558136837 "3"^^ . _:b558137053 . _:b558137038 . _:b558137683 "2"^^ . _:b558136730 . _:b558137427 . _:b558136836 "3"^^ . _:b558137682 "2"^^ . _:b558136839 "3"^^ . _:b558138083 . _:b558137693 "2"^^ . _:b558136838 "3"^^ . . _:b558137692 "2"^^ . _:b558136503 . _:b558136801 . . _:b558136833 "3"^^ . _:b558137695 "2"^^ . _:b558137106 . _:b558136832 "3"^^ . _:b558137694 "2"^^ . _:b558136301 . _:b558137500 . _:b558136835 "3"^^ . _:b558137689 "2"^^ . . _:b558136834 "3"^^ . _:b558137688 "2"^^ . _:b558136845 "3"^^ . _:b558136737 . _:b558136721 . _:b558137691 "2"^^ . _:b558136844 "3"^^ . _:b558136866 . _:b558137690 "2"^^ . _:b558137406 . _:b558136847 "3"^^ . _:b558136629 . _:b558137701 "2"^^ . _:b558136846 "3"^^ . . _:b558137700 "2"^^ . _:b558137563 . _:b558136537 . _:b558136841 "3"^^ . _:b558138025 . . _:b558137703 "2"^^ . . . _:b558136840 "3"^^ . _:b558137973 . _:b558137702 "2"^^ . . _:b558136843 "3"^^ . _:b558137697 "2"^^ . _:b558138068 . _:b558136842 "3"^^ . . _:b558137696 "2"^^ . _:b558136853 "3"^^ . _:b558137231 . _:b558137699 "2"^^ . _:b558137869 . . _:b558136852 "3"^^ . _:b558137780 . . _:b558137698 "2"^^ . . _:b558136381 . _:b558136855 "3"^^ . _:b558137709 "2"^^ . . _:b558136854 "3"^^ . _:b558136552 . _:b558136996 . _:b558137708 "2"^^ . _:b558136439 . _:b558136849 "3"^^ . _:b558137711 "2"^^ . _:b558136848 "3"^^ . _:b558137710 "2"^^ . _:b558136851 "3"^^ . _:b558137705 "2"^^ . . _:b558136943 . . _:b558136850 "3"^^ . _:b558137704 "2"^^ . _:b558136861 "3"^^ . _:b558137688 . _:b558137707 "2"^^ . _:b558136860 "3"^^ . _:b558138055 . _:b558136564 . _:b558137706 "2"^^ . . _:b558136863 "3"^^ . . _:b558137717 "2"^^ . _:b558136862 "3"^^ . . . . _:b558137716 "2"^^ . . _:b558136857 "3"^^ . . _:b558137719 "2"^^ . _:b558136856 "3"^^ . . _:b558137718 "2"^^ . . _:b558136859 "3"^^ . . _:b558137713 "2"^^ . _:b558136858 "3"^^ . _:b558137923 . _:b558136615 . . _:b558137712 "2"^^ . . _:b558137987 . _:b558136869 "3"^^ . _:b558137715 "2"^^ . _:b558138099 . _:b558136868 "3"^^ . _:b558136531 . _:b558137714 "2"^^ . _:b558136871 "3"^^ . _:b558137725 "2"^^ . . _:b558136870 "3"^^ . _:b558137259 . _:b558137724 "2"^^ . . _:b558136865 "3"^^ . _:b558137727 "2"^^ . _:b558136864 "3"^^ . _:b558137726 "2"^^ . _:b558136760 . _:b558136867 "3"^^ . . _:b558137721 "2"^^ . . _:b558136866 "3"^^ . _:b558136783 . _:b558137720 "2"^^ . _:b558137811 . _:b558136877 "3"^^ . _:b558136535 . _:b33179858 "whole-genome sequencing using g2/m nuclei" . _:b558137723 "2"^^ . _:b558136876 "3"^^ . . _:b558137722 "2"^^ . _:b558136879 "3"^^ . _:b558137470 . . _:b558138102 . . _:b558137733 "2"^^ . _:b558136878 "3"^^ . . _:b558137732 "2"^^ . _:b558136873 "3"^^ . _:b558137650 . _:b558137735 "2"^^ . _:b558136872 "3"^^ . . _:b558137734 "2"^^ . _:b558136799 . _:b558136875 "3"^^ . _:b558137167 . _:b558137717 . _:b558137729 "2"^^ . _:b558136874 "3"^^ . . . _:b558137728 "2"^^ . _:b558136337 . _:b558136918 . _:b558136885 "3"^^ . _:b558137731 "2"^^ . _:b558136884 "3"^^ . _:b558137730 "2"^^ . . _:b558136887 "3"^^ . _:b558137882 . . _:b558137741 "2"^^ . _:b558136912 . _:b558136886 "3"^^ . _:b558137740 "2"^^ . _:b558136881 "3"^^ . _:b558137743 "2"^^ . . _:b558137385 . _:b558136880 "3"^^ . _:b558136296 . _:b558137742 "2"^^ . _:b558136883 "3"^^ . _:b558136527 . _:b558137737 "2"^^ . . _:b558136882 "3"^^ . . _:b558137736 "2"^^ . _:b558136893 "3"^^ . _:b558137739 "2"^^ . _:b558136892 "3"^^ . _:b558137663 . _:b558137738 "2"^^ . . _:b558136895 "3"^^ . _:b558137749 "2"^^ . . _:b558137168 . _:b558136894 "3"^^ . _:b558137748 "2"^^ . _:b558136889 "3"^^ . _:b558137751 "2"^^ . _:b33179856 . _:b558136888 "3"^^ . _:b558138160 . . _:b558137750 "2"^^ . _:b558136891 "3"^^ . _:b558137745 "2"^^ . _:b558137871 . _:b558136829 . _:b558136890 "3"^^ . _:b558137744 "2"^^ . _:b558136326 . _:b558136901 "3"^^ . _:b558137088 . _:b558137747 "2"^^ . . _:b558136898 . _:b558136900 "3"^^ . . . _:b558137746 "2"^^ . _:b558137050 . _:b558136903 "3"^^ . _:b558137433 . _:b558138127 . _:b558137757 "2"^^ . _:b558136902 "3"^^ . . _:b558137756 "2"^^ . . _:b558136897 "3"^^ . _:b558137759 "2"^^ . _:b558136896 "3"^^ . . _:b33179857 "While TCGA studies>>39<<\u201341 report increased mutation frequencies, it remains unclear whether these mutations accumulate over many cell divisions (at a normal error rate) or through an increased mutation rate." . _:b558137758 "2"^^ . _:b558136899 "3"^^ . . _:b558137753 "2"^^ . _:b558136898 "3"^^ . _:b558137752 "2"^^ . . _:b558136909 "3"^^ . _:b558137755 "2"^^ . _:b558138101 . _:b558136908 "3"^^ . _:b558137754 "2"^^ . . _:b558136911 "3"^^ . . _:b558137765 "2"^^ . . _:b558136910 "3"^^ . _:b558138002 . _:b558137764 "2"^^ . _:b558137921 . _:b558136905 "3"^^ . _:b558136376 . _:b558137767 "2"^^ . _:b558137989 . _:b558136904 "3"^^ . _:b558137766 "2"^^ . . . _:b558136907 "3"^^ . _:b558137761 "2"^^ . _:b558136649 . _:b558136906 "3"^^ . _:b558137478 . . _:b558137760 "2"^^ . . _:b558138086 . _:b558136917 "3"^^ . _:b558137763 "2"^^ . _:b558137636 . _:b558136916 "3"^^ . . _:b558137762 "2"^^ . _:b558136919 "3"^^ . _:b558137773 "2"^^ . . _:b558137451 . _:b558136918 "3"^^ . . . _:b558137772 "2"^^ . . . _:b558136913 "3"^^ . _:b558137775 "2"^^ . _:b558136366 . _:b558136912 "3"^^ . _:b558136404 . _:b558136800 . _:b558137774 "2"^^ . _:b558136915 "3"^^ . _:b558137769 "2"^^ . _:b558136914 "3"^^ . _:b558136394 . _:b558137768 "2"^^ . _:b558136925 "3"^^ . _:b558136940 . _:b558137771 "2"^^ . _:b558136924 "3"^^ . _:b558137770 "2"^^ . _:b558136927 "3"^^ . _:b558137781 "2"^^ . _:b558136926 "3"^^ . _:b558137780 "2"^^ . _:b558136921 "3"^^ . _:b558137783 "2"^^ . _:b558137801 . . . _:b558136920 "3"^^ . _:b558137782 "2"^^ . . _:b558136923 "3"^^ . _:b558137777 "2"^^ . _:b558136723 . _:b558136922 "3"^^ . _:b558137242 . _:b558136591 . _:b558137776 "2"^^ . . _:b558136933 "3"^^ . _:b558137779 "2"^^ . _:b558136932 "3"^^ . _:b558137070 . _:b558137778 "2"^^ . _:b558136935 "3"^^ . _:b558137789 "2"^^ . _:b558136553 . _:b558136934 "3"^^ . . _:b558137788 "2"^^ . _:b558136929 "3"^^ . _:b558137390 . _:b558137791 "2"^^ . _:b558137782 . _:b558136928 "3"^^ . _:b558136970 . _:b558137790 "2"^^ . _:b558136931 "3"^^ . . _:b558138115 . _:b558137785 "2"^^ . _:b558136722 . _:b558136930 "3"^^ . . _:b558137784 "2"^^ . . _:b558136941 "3"^^ . _:b558137135 . . _:b558137386 . _:b558137787 "2"^^ . _:b558136244 . _:b33179885 . _:b558136940 "3"^^ . _:b558137532 . _:b558137639 . _:b558137786 "2"^^ . . _:b558138021 . _:b558136943 "3"^^ . _:b558137329 . _:b558137797 "2"^^ . _:b558136942 "3"^^ . _:b558137489 . _:b558137796 "2"^^ . . _:b558136937 "3"^^ . . _:b558137799 "2"^^ . _:b558136936 "3"^^ . _:b558137798 "2"^^ . _:b558136939 "3"^^ . _:b558137793 "2"^^ . _:b558136938 "3"^^ . _:b558136592 . _:b558137792 "2"^^ . _:b558136949 "3"^^ . . _:b558137795 "2"^^ . _:b558137813 . _:b558136948 "3"^^ . _:b558137794 "2"^^ . _:b558136951 "3"^^ . _:b558137034 . . _:b558137805 "2"^^ . . _:b558136950 "3"^^ . _:b558137153 . _:b558137804 "2"^^ . _:b558136945 "3"^^ . _:b558137978 . _:b558137320 . _:b558137807 "2"^^ . _:b558136944 "3"^^ . . _:b558137806 "2"^^ . . _:b558136947 "3"^^ . _:b558137404 . _:b558137801 "2"^^ . . _:b558136532 . _:b558136946 "3"^^ . _:b558137800 "2"^^ . _:b558136957 "3"^^ . _:b558137803 "2"^^ . _:b558136956 "3"^^ . . _:b558137802 "2"^^ . . _:b558136959 "3"^^ . . _:b558137813 "2"^^ . _:b558136958 "3"^^ . _:b558136999 . _:b558137812 "2"^^ . _:b558136953 "3"^^ . _:b558137815 "2"^^ . _:b558136952 "3"^^ . _:b33179884 "experimentally derived parameters for cell birth rates (Ki-67 staining), cell death rates (caspase-3 staining), total tumor cell numbers (flow-sorting cell counts) and the tumor mass doubling time for invasive carcinomas (mean=168 days)>>23<<\u201325 (methods). We modeled data for a series of mutation rates and compared the data to the empirical single cell mutation frequency distributions (Supplementary Table 8)." . _:b558137814 "2"^^ . . _:b558136955 "3"^^ . _:b558137797 . _:b558137809 "2"^^ . _:b558136954 "3"^^ . _:b558137808 "2"^^ . _:b558137441 . _:b558136965 "3"^^ . _:b558137811 "2"^^ . _:b558136964 "3"^^ . _:b558137291 . _:b558137334 . _:b558137810 "2"^^ . _:b558136967 "3"^^ . _:b558136512 . _:b558137821 "2"^^ . _:b558137631 . _:b558136966 "3"^^ . _:b558137820 "2"^^ . _:b558136961 "3"^^ . _:b558137823 "2"^^ . _:b558136960 "3"^^ . _:b558136423 . _:b558137822 "2"^^ . _:b558136659 . _:b558136963 "3"^^ . _:b558136538 . _:b558137817 "2"^^ . . _:b558136962 "3"^^ . _:b558137816 "2"^^ . _:b558138111 . _:b558136463 . _:b558137992 . _:b558136973 "3"^^ . _:b558137819 "2"^^ . . _:b558136499 . . _:b558136972 "3"^^ . . _:b558137818 "2"^^ . _:b558136975 "3"^^ . . _:b558137474 . _:b558137829 "2"^^ . _:b558136571 . _:b558136974 "3"^^ . _:b558137828 "2"^^ . _:b558136813 . . _:b558136969 "3"^^ . _:b558137831 "2"^^ . . _:b558137618 . _:b558136968 "3"^^ . . _:b558137830 "2"^^ . _:b558137353 . . . _:b558137564 . . _:b558136971 "3"^^ . . . _:b558137825 "2"^^ . _:b558136970 "3"^^ . . . _:b558137824 "2"^^ . . _:b558136981 "3"^^ . _:b558137827 "2"^^ . _:b558136980 "3"^^ . _:b558137826 "2"^^ . _:b558136983 "3"^^ . _:b33179882 "Duplex libraries were constructed from bulk tissue to reduce the error rate of next-generation sequencing>>10<<. Custom capture platforms were designed to target mutations detected in the single cells of the ER and TNBC tumors (methods). Targeted deep-sequencing (116,952X) was performed in the ER tumor resulting in a single molecule coverage depth" . _:b558137837 "2"^^ . . . _:b558136982 "3"^^ . _:b558137836 "2"^^ . _:b558136618 . _:b558136977 "3"^^ . . . . _:b558136361 . _:b558137839 "2"^^ . _:b558136557 . _:b558136976 "3"^^ . _:b558136982 . _:b558137838 "2"^^ . . _:b558138031 . _:b558136979 "3"^^ . . _:b558137833 "2"^^ . . _:b558136978 "3"^^ . . _:b558137832 "2"^^ . . _:b558136989 "3"^^ . _:b558137835 "2"^^ . _:b558137226 . _:b558136988 "3"^^ . _:b558137834 "2"^^ . . _:b558138155 . _:b558136991 "3"^^ . _:b558137845 "2"^^ . _:b558136307 . _:b558136990 "3"^^ . _:b558137844 "2"^^ . _:b558136985 "3"^^ . _:b558137847 "2"^^ . . _:b558136984 "3"^^ . _:b558137846 "2"^^ . _:b558137908 . _:b558136987 "3"^^ . _:b558136915 . _:b558137633 . _:b558137841 "2"^^ . _:b558136549 . _:b558136986 "3"^^ . . _:b558137840 "2"^^ . . . _:b558136997 "3"^^ . _:b558137843 "2"^^ . _:b33179855 "Our data also has important implications for the mutator phenotype, which posits that tumor evolution is driven by increased mutation rates>>34<<,38. While TCGA studies39\u201341 report increased mutation frequencies, it remains unclear whether these mutations accumulate over many cell divisions (at a normal error rate) or through an increased mutation rate. Our TNBC data suggest an" . . _:b558136996 "3"^^ . . _:b558137842 "2"^^ . _:b558136999 "3"^^ . _:b558137853 "2"^^ . _:b558136998 "3"^^ . _:b558137852 "2"^^ . _:b558136488 . . _:b558136993 "3"^^ . . _:b558137855 "2"^^ . . _:b558136992 "3"^^ . _:b558138064 . _:b558136492 . _:b558137854 "2"^^ . _:b558136995 "3"^^ . _:b558137683 . _:b558137849 "2"^^ . _:b558136434 . _:b558136994 "3"^^ . _:b558137366 . _:b558137848 "2"^^ . _:b558137005 "3"^^ . _:b558137851 "2"^^ . . . _:b558138131 . _:b558137004 "3"^^ . . _:b558137850 "2"^^ . . _:b558137007 "3"^^ . . . . . _:b558137006 "3"^^ . _:b558137814 . _:b558137845 . _:b558137001 "3"^^ . _:b558137000 "3"^^ . _:b558137003 "3"^^ . _:b33179875 . . _:b558137002 "3"^^ . _:b558137444 . _:b558137309 . _:b558137013 "3"^^ . _:b558137199 . _:b558137962 . _:b558137012 "3"^^ . _:b558137015 "3"^^ . _:b558137490 . . _:b558137014 "3"^^ . . _:b558137268 . _:b558137009 "3"^^ . _:b558137008 "3"^^ . _:b558137011 "3"^^ . _:b558137010 "3"^^ . _:b558137021 "3"^^ . _:b558136967 . _:b558138015 . . _:b558137020 "3"^^ . _:b558137023 "3"^^ . _:b558138080 . _:b558137612 . _:b558137422 . _:b558137185 . _:b558137022 "3"^^ . _:b558137017 "3"^^ . _:b558137064 . _:b558136965 . _:b558137016 "3"^^ . _:b558137122 . . _:b33179885 "These data are similar to the error rates reported for normal cells, which are approximately 0.6 mutations per cell division (error rate = 1e-10) >>26<<\u201328. In contrast, our modeling suggests a mutation rate of MR= 8 for the TNBC tumor, suggesting a 13.3X fold increase relative to normal cells (Fig. 4e)." . _:b558137019 "3"^^ . _:b558137018 "3"^^ . . _:b558137029 "3"^^ . . _:b558137499 . _:b558137028 "3"^^ . _:b558138045 . _:b558136809 . _:b558137031 "3"^^ . _:b558137657 . . _:b558137030 "3"^^ . _:b558137686 . _:b558137025 "3"^^ . . _:b558137024 "3"^^ . _:b558137027 "3"^^ . _:b558137026 "3"^^ . . . _:b558137037 "3"^^ . _:b558137036 "3"^^ . _:b558137859 . . . _:b558137039 "3"^^ . _:b558136452 . _:b558137038 "3"^^ . . . _:b558137033 "3"^^ . . . _:b558137032 "3"^^ . . _:b558137417 . _:b558137035 "3"^^ . _:b558137034 "3"^^ . . . _:b558137045 "3"^^ . _:b558137709 . _:b558137044 "3"^^ . . _:b558136798 . . _:b558137047 "3"^^ . _:b558136261 . _:b558136707 . _:b558137046 "3"^^ . _:b558137041 "3"^^ . . . _:b558137040 "3"^^ . _:b558136958 . _:b558136304 . _:b558137043 "3"^^ . _:b558137548 . _:b558137042 "3"^^ . . . _:b558137053 "3"^^ . _:b558137614 . _:b558137052 "3"^^ . . . _:b558137055 "3"^^ . . . _:b558137054 "3"^^ . _:b558137851 . _:b558137779 . . _:b558137049 "3"^^ . _:b558137318 . . _:b558137048 "3"^^ . . _:b33179884 . _:b558137051 "3"^^ . _:b558137050 "3"^^ . . _:b558137061 "3"^^ . . _:b558137060 "3"^^ . . _:b558137063 "3"^^ . _:b558136704 . _:b558137621 . . _:b558137062 "3"^^ . _:b558136676 . _:b558137057 "3"^^ . _:b558137459 . _:b558137361 . _:b558137897 . _:b558137056 "3"^^ . _:b558136808 . _:b558137059 "3"^^ . _:b558137516 . _:b558137058 "3"^^ . _:b558137895 . _:b558136744 . . _:b558137069 "3"^^ . . _:b558137068 "3"^^ . _:b558137907 . _:b558137071 "3"^^ . . _:b558137331 . _:b558137070 "3"^^ . _:b558137065 "3"^^ . _:b558137064 "3"^^ . . _:b558137001 . _:b558137067 "3"^^ . _:b558136902 . _:b558137066 "3"^^ . _:b558137396 . . _:b558137362 . . _:b558137077 "3"^^ . _:b558136474 . . _:b558137076 "3"^^ . _:b558137363 . . . . _:b558137079 "3"^^ . _:b558136565 . _:b558137078 "3"^^ . _:b558136695 . _:b558137293 . _:b558137073 "3"^^ . _:b558137690 . . _:b558137494 . _:b558137072 "3"^^ . _:b558137836 . _:b558137075 "3"^^ . . _:b558137074 "3"^^ . _:b558136900 . _:b558137085 "3"^^ . _:b558136717 . _:b558137236 . _:b558136473 . _:b558137084 "3"^^ . _:b558137087 "3"^^ . _:b558136785 . _:b558137086 "3"^^ . _:b558136895 . _:b558137081 "3"^^ . _:b558137590 . _:b558137080 "3"^^ . _:b558137920 . . _:b558137083 "3"^^ . _:b558137082 "3"^^ . _:b558137093 "3"^^ . _:b558137092 "3"^^ . _:b558136955 . . _:b558137095 "3"^^ . . _:b558137094 "3"^^ . _:b558137089 "3"^^ . _:b558137088 "3"^^ . . _:b558137091 "3"^^ . . _:b558137090 "3"^^ . _:b558137101 "3"^^ . . _:b33179883 "mathematical modeling of the mutation rates" . _:b558137766 . _:b558137100 "3"^^ . _:b558138139 . _:b558137103 "3"^^ . _:b558137102 "3"^^ . _:b558137097 "3"^^ . _:b558137096 "3"^^ . _:b558137880 . _:b558137099 "3"^^ . _:b558136834 . . . _:b558137098 "3"^^ . . _:b558137024 . _:b558136611 . _:b558137109 "3"^^ . _:b558137488 . _:b558137693 . _:b558136746 . _:b558137108 "3"^^ . _:b558137579 . _:b558137111 "3"^^ . . _:b558137110 "3"^^ . . _:b558137105 "3"^^ . . . _:b558136833 . _:b558137104 "3"^^ . . . _:b558137107 "3"^^ . . . _:b558137106 "3"^^ . _:b558137684 . _:b558137117 "3"^^ . . _:b558137116 "3"^^ . _:b558137356 . _:b558137119 "3"^^ . _:b558138042 . _:b558137775 . _:b558137118 "3"^^ . _:b558138039 . _:b558137113 "3"^^ . _:b558136705 . _:b558137112 "3"^^ . _:b558137115 "3"^^ . _:b558137114 "3"^^ . _:b558137936 . _:b558136461 . _:b558137125 "3"^^ . _:b558137260 . _:b558137124 "3"^^ . _:b558137665 . _:b558137127 "3"^^ . _:b558137126 "3"^^ . _:b558138129 . . _:b558138158 . _:b558137121 "3"^^ . _:b558137885 . . _:b33179860 "This approach provides an advantage over using chemical inhibitors to induce polyploidy in single cells12,>>13<< because it does not require live cells." . _:b558137120 "3"^^ . . _:b558137855 . _:b558137123 "3"^^ . _:b558136457 . _:b558136972 . _:b558137122 "3"^^ . _:b558137437 . _:b558137133 "3"^^ . . _:b558136561 . _:b558137132 "3"^^ . _:b558137135 "3"^^ . . _:b558136476 . . _:b558137134 "3"^^ . _:b558137129 "3"^^ . _:b558136682 . . _:b558137128 "3"^^ . . _:b558137131 "3"^^ . _:b558137415 . . _:b558137130 "3"^^ . _:b558137935 . _:b558137141 "3"^^ . _:b558136390 . _:b558136718 . _:b558137867 . _:b558137140 "3"^^ . _:b558137143 "3"^^ . _:b33179854 "While this question has been studied for decades in bacteria>>37<< it remains poorly understood in human cancers." . _:b558137142 "3"^^ . _:b558137137 "3"^^ . . _:b558137136 "3"^^ . _:b558137139 "3"^^ . _:b558137131 . _:b558137960 . _:b558137138 "3"^^ . _:b558136973 . _:b558137149 "3"^^ . _:b558137148 "3"^^ . _:b558137738 . _:b558137151 "3"^^ . . . _:b558137150 "3"^^ . _:b558137145 "3"^^ . _:b558137144 "3"^^ . _:b558137147 "3"^^ . . _:b33179880 . _:b558136292 . _:b558137146 "3"^^ . _:b558137157 "3"^^ . . _:b558137018 . . _:b558137156 "3"^^ . _:b558137159 "3"^^ . . _:b558137158 "3"^^ . . . _:b558138065 . _:b558137153 "3"^^ . . _:b558137152 "3"^^ . _:b558137771 . . _:b558138118 . _:b558137077 . _:b558137155 "3"^^ . . _:b558137154 "3"^^ . . . _:b558137165 "2"^^ . . _:b558137130 . . _:b558137164 "2"^^ . _:b558136444 . _:b558136860 . _:b558137167 "2"^^ . . _:b558137166 "2"^^ . . _:b558137161 "3"^^ . _:b558138032 . _:b558137114 . _:b558137957 . . _:b558137160 "3"^^ . _:b558136281 . _:b558138082 . _:b558137163 "2"^^ . _:b558137760 . _:b558137162 "3"^^ .