Analysis of the Cancer Imprintome and its Associated Long Non-Coding RNAs

点击翻译按钮获取中文摘要

It has become clear that allel-specific methylation — and allel-specific gene expression as one of its important consequences — are much more wide-spread than imprinting. Nevertheless, a global view on the prevalence and importance of this phenomenon is lacking. Here, we propose to survey these phenomena systematically both from an evolutionary perspective and with the aim of obtaining a better understanding of the impact of monoallelic effects in cancer. An important aspect of the proposed work program is to develop a readily usable toolkit of workflows for the detection of monoallelic DNA methylation and monoallelic transcription, and for the integration of these two important data types. The project is designed to re-use the extensive bisulfite and RNA-seq data sets already publicly available from large-scale coordinated efforts such as the International Cancer Sequencing Consortium. In order to cover the evolutionary dimension, available data from several mammalian species will be considered in direct comparison to human and mouse data. Elaborate regulated DNA methylation is not limited to mammals, however, but also plays a key role in social insects. We will therefore also consider allel-specific effects and caste-differences in arthropod species, in particular in bees and ants. Sex-specific gene expression and DNA methylation has been implicated in differences in diagnostic efficiency and clinical outcomes in a wide array of disease entities. In the context of the proposed research we will therefore assess sex-specific differences of allel-specific effects, both with regards to DNA methylation and transcriptional output. The aim of the project is to provide a solid understanding of distribution, variability, and evolutionary plasticity of allel-specific effects at a genome-wide level.