Modeling cancer rearrangement landscapes.
Modeling cancer rearrangement landscapes.
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DOI：
10.1016/j.coisb.2016.12.005
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发表时间：
2017-02-01
影响因子：
3.7
通讯作者：
Imielinski, Marcin
中科院分区：
文献类型：
--
作者：
Maciejowski, John;Imielinski, Marcin
癌症基因组序列包含体细胞突变过程的足迹，其在大型肿瘤测序数据集中的分析已经揭示了新的突变特征、变异地形的相关特征和复杂事件。这些分析结果中的许多还没有与几十年来在受控模型系统中进行的机械基因组完整性研究相协调。然而，结合计算建模、数据分析和高通量测序的新一代基因组完整性实验正在出现，以将机制与模式联系起来。相反，评估特定基因组完整性假设的定量足迹的分析研究将在将自然发生的突变模式与特定机制模型的预测相拟合方面至关重要。这种定量和机制的研究将形成基因组完整性的新兴系统生物学的基础。
Cancer genome sequences contain footprints of somatic mutational processes, whose analysis in large tumor sequencing datasets has revealed novel mutational signatures, correlative features of variant topography, and complex events. Many of these analytic results have yet to reconciled with decades of mechanistic genome integrity research performed in controlled model systems. However, a new generation of genome-integrity experiments combining computational modeling, data analytics, and high-throughput sequencing are emerging to link mechanisms to patterns. Conversely, analytic studies evaluating quantitative footprints of specific genome integrity hypotheses will be critical in fitting naturally occurring mutational patterns to the predictions of a particular mechanistic model. Such quantitative and mechanistic studies will form the foundation of an emerging systems biology of genome integrity.