HiTIMED: hierarchical tumor immune microenvironment epigenetic deconvolution for accurate cell type resolution in the tumor microenvironment using tumor-type-specific DNA methylation data.
J Transl Med
; 20(1): 516, 2022 11 08.
Article
em En
| MEDLINE
| ID: mdl-36348337
ABSTRACT
BACKGROUND:
Cellular compositions of solid tumor microenvironments are heterogeneous, varying across patients and tumor types. High-resolution profiling of the tumor microenvironment cell composition is crucial to understanding its biological and clinical implications. Previously, tumor microenvironment gene expression and DNA methylation-based deconvolution approaches have been shown to deconvolve major cell types. However, existing methods lack accuracy and specificity to tumor type and include limited identification of individual cell types.RESULTS:
We employed a novel tumor-type-specific hierarchical model using DNA methylation data to deconvolve the tumor microenvironment with high resolution, accuracy, and specificity. The deconvolution algorithm is named HiTIMED. Seventeen cell types from three major tumor microenvironment components can be profiled (tumor, immune, angiogenic) by HiTIMED, and it provides tumor-type-specific models for twenty carcinoma types. We demonstrate the prognostic significance of cell types that other tumor microenvironment deconvolution methods do not capture.CONCLUSION:
We developed HiTIMED, a DNA methylation-based algorithm, to estimate cell proportions in the tumor microenvironment with high resolution and accuracy. HiTIMED deconvolution is amenable to archival biospecimens providing high-resolution profiles enabling to study of clinical and biological implications of variation and composition of the tumor microenvironment.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
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Neoplasias
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article