Ancestral inference in tumors: how much can we know?
Ancestral inference in tumors: how much can we know?
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DOI：
10.1016/j.jtbi.2014.05.027
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发表时间：
2014-10-21
影响因子：
2
通讯作者：
Marjoram P
中科院分区：
文献类型：
--
作者：
Zhao J;Siegmund KD;Shibata D;Marjoram P
肿瘤被认为是从单个细胞和基因组开始的。然而，最终肿瘤中的基因组通常是异质的。这种瘤内异质性（ITH）的奥秘尚未被发现，但这种ITH的大部分可能是继发于复制错误。胞嘧啶碱基的甲基化通常表现为ITH，因此可能编码肿瘤的祖先。在这项研究中，我们测量乘客甲基化模式的一个特定的CpG区域在9个结直肠肿瘤的亚硫酸氢盐测序和应用肿瘤发展模型。基于我们的模型，我们能够使用近似贝叶斯计算来检索关于每个肿瘤的祖先的信息。通过一个大型的模拟研究，我们探索的条件下，我们可以估计的模型参数，和第一个转换的细胞的初始状态。最后，我们将我们的分析应用于临床数据，以深入了解肿瘤形成的动力学。
A tumor is thought to start from a single cell and genome. Yet genomes in the final tumor are typically heterogeneous. The mystery of this intratumoral heterogeneity (ITH) has not yet been uncovered, but much of this ITH may be secondary to replication errors. Methylation of cytosine bases often exhibits ITH and therefore may encode the ancestry of the tumor. In this study, we measure the passenger methylation patterns of a specific CpG region in 9 colorectal tumors by bisulfite sequencing and apply a tumor development model. Based on our model, we are able to retrieve information regarding the ancestry of each tumor using approximate Bayesian computation. With a large simulation study we explore the conditions under which we can estimate the model parameters, and the initial state of the first transformed cell. Finally we apply our analysis to clinical data to gain insight into the dynamics of tumor formation.