Using somatic variant richness to mine signals from rare variants in the cancer genome
Using somatic variant richness to mine signals from rare variants in the cancer genome
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DOI：
10.1038/s41467-019-13402-z
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发表时间：
2019-12-03
影响因子：
16.6
通讯作者：
Shen, Ronglai
中科院分区：
文献类型：
--
作者：
Chakraborty, Saptarshi;Arora, Arshi;Shen, Ronglai
迄今为止，在癌症基因组中观察到的体细胞变体的绝大多数是罕见的变体，并且在实践中经常遇到以前未观察到的新肿瘤变体。在这里，我们专注于概率估计遇到这种迄今未见的变种。我们利用统计方法，已在其他领域的研究，特别是在物种估计生态学，计算语言学的词频估计。全外显子组和靶向面板测序数据集的分析揭示了基因之间的变异“丰富度”的实质性变化，这些变异可以用于临床相关问题。我们量化的变异组织协会，并显示出强大的基因特异性，谱系依赖的模式遇到新的变异。这种变异性在很大程度上取决于观察到的罕见变异的比例。我们的研究结果表明，在非常低的频率发生的变异可以隐藏重要的信号，是临床后果。
To date, the vast preponderance of somatic variants observed in the cancer genome have been rare variants, and it is common in practice to encounter in a new tumor variants that have not been observed previously. Here we focus on probability estimation for encountering such hitherto unseen variants. We draw upon statistical methodology that has been developed in other fields of study, notably in species estimation in ecology, and word frequency estimation in computational linguistics. Analysis of whole-exome and targeted panel sequencing data sets reveal substantial variability in variant "richness" between genes that could be harnessed for clinically relevant problems. We quantify the variant-tissue association and show a strong gene-specific, lineage-dependent pattern of encountering new variants. This variability is largely determined by the proportion of observed variants that are rare. Our findings suggest that variants that occur at very low frequencies can harbor important signals that are clinically consequential.