Background: Deciphering proportions of constitutional cell types in tumor tissues is a crucial step for the analysis of tumor heterogeneity and the prediction of response to immunotherapy. In the process of measuring cell population proportions, traditional experimental methods have been greatly hampered by the cost and extensive dropout events. At present, the public availability of large amounts of DNA methylation data makes it possible to use computational methods to predict proportions.
Results: In this paper, we proposed PRMeth, a method to deconvolve tumor mixtures using partially available DNA methylation data. By adopting an iteratively optimized non-negative matrix factorization framework, PRMeth took DNA methylation profiles of a portion of the cell types in the tissue mixtures (including blood and solid tumors) as input to estimate the proportions of all cell types as well as the methylation profiles of unknown cell types simultaneously. We compared PRMeth with five different methods through three benchmark datasets and the results show that PRMeth could infer the proportions of all cell types and recover the methylation profiles of unknown cell types effectively. Then, applying PRMeth to four types of tumors from The Cancer Genome Atlas (TCGA) database, we found that the immune cell proportions estimated by PRMeth were largely consistent with previous studies and met biological significance.
Conclusions: Our method can circumvent the difficulty of obtaining complete DNA methylation reference data and obtain satisfactory deconvolution accuracy, which will be conducive to exploring the new directions of cancer immunotherapy. PRMeth is implemented in R and is freely available from GitHub ( https://github.com/hedingqin/PRMeth ).
Keywords: Cell population proportions; DNA methylation data; Immunotherapy; Non-negative matrix factorization; Tumor heterogeneity.
© 2022. The Author(s).