Shijie C Zheng1,2, Amy P Webster3, Danyue Dong1,2, Andy Feber4, David G Graham4, Roisin Sullivan4, Sarah Jevons4, Laurence B Lovat4, Stephan Beck3, Martin Widschwendter5, Andrew E Teschendorff1,5. 1. 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. 2. University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, PR China. 3. UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street, London WC1E 6BT, UK. 4. Division of Surgery & Interventional Science, UCL, London WC1E 6BT, UK. 5. Department of Women's Cancer, University College London, 74 Huntley Street, London WC1E 6AU, UK.
Abstract
AIM: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. RESULTS: 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. CONCLUSION: 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.
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