CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, 320 Yue Yang Road, Shanghai 200031, PR China.
University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China.
Epigenomics. 2018 Jul;10(7):925-940. doi: 10.2217/epi-2018-0037. Epub 2018 Apr 25.
An outstanding challenge in epigenome studies is the estimation of cell-type proportions in complex epithelial tissues.
MATERIALS & METHODS: Here, we construct and validate a DNA methylation reference and algorithm for complex tissues that contain epithelial, immune and nonimmune stromal cells.
Using this reference, we show that easily accessible tissues such as saliva, buccal and cervix exhibit substantial variation in immune cell (IC) contamination. We further validate our reference in the context of oral cancer, where it correctly predicts an increased IC infiltration in cancer but suppressed in patients with highest smoking exposure. Finally, our method can improve the specificity of differentially methylated CpG calls in epithelial cancer.
The degree and variation of IC contamination in complex epithelial tissues is substantial. We provide a valuable resource and tool for assessing the epithelial purity and IC contamination of samples and for identifying differential methylation in such complex tissues.
在表观基因组学研究中，一个突出的挑战是估计复杂上皮组织中的细胞类型比例。
在这里，我们构建并验证了一种适用于包含上皮细胞、免疫细胞和非免疫基质细胞的复杂组织的 DNA 甲基化参考和算法。
使用该参考，我们表明，唾液、颊和宫颈等易于获取的组织存在显著的免疫细胞（IC）污染差异。我们进一步在口腔癌的背景下验证了我们的参考，其中它正确预测了癌症中 IC 浸润的增加，但在吸烟暴露最高的患者中受到抑制。最后，我们的方法可以提高上皮癌中差异甲基化 CpG 调用的特异性。
复杂上皮组织中 IC 污染的程度和变化是相当大的。我们提供了一个有价值的资源和工具，用于评估样本的上皮纯度和 IC 污染，并识别此类复杂组织中的差异甲基化。
