Neural-net-based cell deconvolution from DNA methylation reveals tumor microenvironment associated with cancer prognosis

• Published in: NAR cancer 2024-06, Vol.6 (2), p.zcae022-zcae022
• Main Authors: Yasumizu, Yoshiaki, Hagiwara, Masaki, Umezu, Yuto, Fuji, Hiroaki, Iwaisako, Keiko, Asagiri, Masataka, Uemoto, Shinji, Nakamura, Yamami, Thul, Sophia, Ueyama, Azumi, Yokoi, Kazunori, Tanemura, Atsushi, Nose, Yohei, Saito, Takuro, Wada, Hisashi, Kakuda, Mamoru, Kohara, Masaharu, Nojima, Satoshi, Morii, Eiichi, Doki, Yuichiro, Sakaguchi, Shimon, Ohkura, Naganari
• Format: Article
• Language: English
• Subjects: Cancer Computational Biology
• ISSN: 2632-8674; 2632-8674
• DOI: 10.1093/narcan/zcae022

DNA methylation is a pivotal epigenetic modification that defines cellular identity. While cell deconvolution utilizing this information is considered useful for clinical practice, current methods for deconvolution are limited in their accuracy and resolution. In this study, we collected DNA methylation data from 945 human samples derived from various tissues and tumor-infiltrating immune cells and trained a neural network model with them. The model, termed MEnet, predicted abundance of cell population together with the detailed immune cell status from bulk DNA methylation data, and showed consistency to those of flow cytometry and histochemistry. MEnet was superior to the existing methods in the accuracy, speed, and detectable cell diversity, and could be applicable for peripheral blood, tumors, cell-free DNA, and formalin-fixed paraffin-embedded sections. Furthermore, by applying MEnet to 72 intrahepatic cholangiocarcinoma samples, we identified immune cell profiles associated with cancer prognosis. We believe that cell deconvolution by MEnet has the potential for use in clinical settings.