Computational genomics and epigenomics to understand metastasis

是什么导致癌细胞转移--细胞从原发肿瘤迁移到其他器官生长--目前还不清楚。令人惊讶的是，转移瘤与原发性肿瘤的基因组比较通常无法识别任何转移驱动突变，我们解释这一点的假设是双重的：（1）表观遗传变化（DNA甲基化和染色质变化）在转移中起关键作用，以及（2）转移演变动力学的复杂性意味着遗传转移驱动因素已经被遗漏。在这个项目中，我们将开发一个计算框架，使强大的识别转移的遗传和表观遗传驱动程序。该框架将基于癌症演变的随机数学模型。该框架将应用于现有的大型多组学多区域测序数据集，以识别结直肠癌转移的驱动因素。

What causes cancer cells to metastasise - cell migration from the primary tumour and growth in other organs - is unknown. Surprisingly, comparison of the genomes of metastases to primary tumours has generally failed to identify any metastasis driver mutations, and our hypothesis to explain this is two-fold: (1) that epigenetic changes (DNA methylation and chromatin changes) have a key role in enabling metastasis, and (2) that the complexity of the metastasis evolutionary dynamics has meant that genetic metastasis drivers have been missed. In this project, we will develop a computational framework that enables the robust identification genetic and epigenetic drivers of metastasis. The framework will be based on stochastic mathematical models of cancer evolution. The framework will be applied to an existing large multi-omic multi-region sequencing dataset to identify drivers of colorectal cancer metastasis.