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DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles

The interaction of CNS tumors with infiltrating lymphocytes plays an important role in their initiation and progression and might be related to therapeutic responses. Gene expression-based methods have been successfully used to characterize the tumor microenvironment. However, methylation data are n...

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Autores principales: Safaei, Sepehr, Mohme, Malte, Niesen, Judith, Schüller, Ulrich, Bockmayr, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216185/
https://www.ncbi.nlm.nih.gov/pubmed/34235002
http://dx.doi.org/10.1080/2162402X.2021.1932365
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author Safaei, Sepehr
Mohme, Malte
Niesen, Judith
Schüller, Ulrich
Bockmayr, Michael
author_facet Safaei, Sepehr
Mohme, Malte
Niesen, Judith
Schüller, Ulrich
Bockmayr, Michael
author_sort Safaei, Sepehr
collection PubMed
description The interaction of CNS tumors with infiltrating lymphocytes plays an important role in their initiation and progression and might be related to therapeutic responses. Gene expression-based methods have been successfully used to characterize the tumor microenvironment. However, methylation data are now increasingly used for molecular diagnostics and there are currently only few methods to infer information about the microenvironment from this data type. Using an approach based on differential methylation and principal component analysis, we developed DIMEimmune (Differential Methylation Analysis for Immune Cell Estimation) to estimate CD4(+) and CD8(+) T cell abundance as well as tumor-infiltrating lymphocytes (TILs) scores from bulk methylation data. Well-established approaches based on gene expression data and immunohistochemistry-based lymphocyte counts were used as benchmarks. The comparison of DIMEimmune to the previously published MethylCIBERSORT and MeTIL algorithms showed an improved correlation with both gene expression-based and immunohistological results across different brain tumor types. Further, we applied our method to large datasets of glioma, medulloblastoma, atypical teratoid/rhabdoid tumors (ATRTs) and ependymoma. High-grade gliomas showed higher scores of tumor-infiltrating lymphocytes than lower-grade gliomas. There were overall only few tumor-infiltrating lymphocytes in medulloblastoma subgroups. ATRTs were highly infiltrated by lymphocytes, most prominently in the MYC subgroup. DIMEimmune-based estimates of TILs were a significant prognostic factor in the overall cohort of gliomas and medulloblastomas, but not within methylation-based diagnostic subgroups. To conclude, DIMEimmune allows for robust estimates of TIL abundance and might contribute to establishing them as a prognostic or predictive factor in future studies of CNS tumors.
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spelling pubmed-82161852021-07-06 DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles Safaei, Sepehr Mohme, Malte Niesen, Judith Schüller, Ulrich Bockmayr, Michael Oncoimmunology Original Research The interaction of CNS tumors with infiltrating lymphocytes plays an important role in their initiation and progression and might be related to therapeutic responses. Gene expression-based methods have been successfully used to characterize the tumor microenvironment. However, methylation data are now increasingly used for molecular diagnostics and there are currently only few methods to infer information about the microenvironment from this data type. Using an approach based on differential methylation and principal component analysis, we developed DIMEimmune (Differential Methylation Analysis for Immune Cell Estimation) to estimate CD4(+) and CD8(+) T cell abundance as well as tumor-infiltrating lymphocytes (TILs) scores from bulk methylation data. Well-established approaches based on gene expression data and immunohistochemistry-based lymphocyte counts were used as benchmarks. The comparison of DIMEimmune to the previously published MethylCIBERSORT and MeTIL algorithms showed an improved correlation with both gene expression-based and immunohistological results across different brain tumor types. Further, we applied our method to large datasets of glioma, medulloblastoma, atypical teratoid/rhabdoid tumors (ATRTs) and ependymoma. High-grade gliomas showed higher scores of tumor-infiltrating lymphocytes than lower-grade gliomas. There were overall only few tumor-infiltrating lymphocytes in medulloblastoma subgroups. ATRTs were highly infiltrated by lymphocytes, most prominently in the MYC subgroup. DIMEimmune-based estimates of TILs were a significant prognostic factor in the overall cohort of gliomas and medulloblastomas, but not within methylation-based diagnostic subgroups. To conclude, DIMEimmune allows for robust estimates of TIL abundance and might contribute to establishing them as a prognostic or predictive factor in future studies of CNS tumors. Taylor & Francis 2021-06-17 /pmc/articles/PMC8216185/ /pubmed/34235002 http://dx.doi.org/10.1080/2162402X.2021.1932365 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Safaei, Sepehr
Mohme, Malte
Niesen, Judith
Schüller, Ulrich
Bockmayr, Michael
DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title_full DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title_fullStr DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title_full_unstemmed DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title_short DIMEimmune: Robust estimation of infiltrating lymphocytes in CNS tumors from DNA methylation profiles
title_sort dimeimmune: robust estimation of infiltrating lymphocytes in cns tumors from dna methylation profiles
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216185/
https://www.ncbi.nlm.nih.gov/pubmed/34235002
http://dx.doi.org/10.1080/2162402X.2021.1932365
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