Cervical and anal carcinoma are neoplastic diseases with various intraepithelial neoplasia stages. The underlying mechanisms for cancer initiation and progression have not been fully revealed. DNA methylation has been shown to be aberrantly regulated during tumorigenesis in anal and cervical carcinoma, revealing the important roles of DNA methylation signaling as a biomarker to distinguish cancer stages in clinics. In this research, several machine learning methods were used to analyze the methylation profiles on anal and cervical carcinoma samples, which were divided into three classes representing various stages of tumor progression. Advanced feature selection methods, including Boruta, LASSO, LightGBM, and MCFS, were used to select methylation features that are highly correlated with cancer progression. Some methylation probes including cg01550828 and its corresponding gene RNF168 have been reported to be associated with human papilloma virus-related anal cancer. As for biomarkers for cervical carcinoma, cg27012396 and its functional gene HDAC4 were confirmed to regulate the glycolysis and survival of hypoxic tumor cells in cervical carcinoma. Furthermore, we developed effective classifiers for identifying various tumor stages and derived classification rules that reflect the quantitative impact of methylation on tumorigenesis. The current study identified methylation signals associated with the development of cervical and anal carcinoma at qualitative and quantitative levels using advanced machine learning methods.
CD19-targeted CAR T cell immunotherapy has exceptional efficacy for the treatment of B-cell malignancies. B-cell acute lymphocytic leukemia and non-Hodgkin’s lymphoma are two common B-cell malignancies with high recurrence rate and are refractory to cure. Although CAR T-cell immunotherapy overcomes the limitations of conventional treatments for such malignancies, failure of treatment and tumor recurrence remain common. In this study, we searched for important methylation signatures to differentiate CAR-transduced and untransduced T cells from patients with acute lymphoblastic leukemia and non-Hodgkin’s lymphoma. First, we used three feature ranking methods, namely, Monte Carlo feature selection, light gradient boosting machine, and least absolute shrinkage and selection operator, to rank all methylation features in order of their importance. Then, the incremental feature selection method was adopted to construct efficient classifiers and filter the optimal feature subsets. Some important methylated genes, namely, SERPINB6, ANK1, PDCD5, DAPK2, and DNAJB6, were identified. Furthermore, the classification rules for distinguishing different classes were established, which can precisely describe the role of methylation features in the classification. Overall, we applied advanced machine learning approaches to the high-throughput data, investigating the mechanism of CAR T cells to establish the theoretical foundation for modifying CAR T cells.
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