Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology.

Autor:	Sasiain I; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22381, Sweden., Nacer DF; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22381, Sweden.; Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund 22381, Sweden., Aine M; Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund 22381, Sweden., Veerla S; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22381, Sweden.; Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund 22381, Sweden., Staaf J; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund 22381, Sweden.; Division of Oncology, Department of Clinical Sciences Lund, Lund University, Lund 22381, Sweden.
Jazyk:	angličtina
Zdroj:	NAR genomics and bioinformatics [NAR Genom Bioinform] 2024 Nov 04; Vol. 6 (4), pp. lqae146. Date of Electronic Publication: 2024 Nov 04 (Print Publication: 2024).
DOI:	10.1093/nargab/lqae146
Abstrakt:	Epigenetic deregulation through altered DNA methylation is a fundamental feature of tumorigenesis, but tumor data from bulk tissue samples contain different proportions of malignant and non-malignant cells that may confound the interpretation of DNA methylation values. The adjustment of DNA methylation data based on tumor purity has been proposed to render both genome-wide and gene-specific analyses more precise, but it requires sample purity estimates. Here we present PureBeta, a single-sample statistical framework that uses genome-wide DNA methylation data to first estimate sample purity and then adjust methylation values of individual CpGs to correct for sample impurity. Purity values estimated with the algorithm have high correlation (>0.8) to reference values obtained from DNA sequencing when applied to samples from breast carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Methylation beta values adjusted based on purity estimates have a more binary distribution that better reflects theoretical methylation states, thus facilitating improved biological inference as shown for BRCA1 in breast cancer. PureBeta is a versatile tool that can be used for different Illumina DNA methylation arrays and can be applied to individual samples of different cancer types to enhance biological interpretability of methylation data. (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
Databáze:	MEDLINE
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