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Identifying simultaneous rearrangements in cancer genomes

机译:识别癌症基因组中的同时重排

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摘要

MotivationThe traditional view of cancer evolution states that a cancer genome accumulates a sequential ordering of mutations over a long period of time. However, in recent years it has been suggested that a cancer genome may instead undergo a one-time catastrophic event, such as chromothripsis, where a large number of mutations instead occur simultaneously. A number of potential signatures of chromothripsis have been proposed. In this work, we provide a rigorous formulation and analysis of the ‘ability to walk the derivative chromosome’ signature originally proposed by Korbel and Campbell. In particular, we show that this signature, as originally envisioned, may not always be present in a chromothripsis genome and we provide a precise quantification of under what circumstances it would be present. We also propose a variation on this signature, the H/T alternating fraction, which allows us to overcome some of the limitations of the original signature.
机译:动机关于癌症进化的传统观点认为,癌症基因组在很长一段时间内会累积突变的顺序排列。然而,近年来已经提出,癌症基因组可能替代地经历一次灾难性事件,例如色杆菌病,其中大量突变同时发生。已经提出了许多潜在的色杆菌病特征。在这项工作中,我们对Korbel和Campbell最初提出的“走衍生染色体的能力”签名进行了严格的表述和分析。特别是,我们证明了这种签名,如最初设想的那样,可能并不总是存在于拟除霉菌基因组中,并且我们提供了在什么情况下会出现的精确定量。我们还提出了对此签名的一种变体,即H / T交替分数,它使我们能够克服原始签名的某些限制。

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