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

Sasiain, Inaki LU orcid ; Nacer, Deborah F. LU orcid ; Aine, Mattias LU ; Veerla, Srinivas LU orcid and Staaf, Johan LU orcid (2024) In NAR Genomics and Bioinformatics 6(4).
Abstract
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... (More)
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. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NAR Genomics and Bioinformatics
volume
6
issue
4
article number
lqae146
publisher
Oxford University Press
external identifiers
  • pmid:39498434
  • scopus:85208655654
ISSN
2631-9268
DOI
10.1093/nargab/lqae146
language
English
LU publication?
yes
id
cab3897e-a830-469e-96c5-b8f1ee1fcd2f
date added to LUP
2024-11-19 13:23:40
date last changed
2025-04-04 14:21:36
@article{cab3897e-a830-469e-96c5-b8f1ee1fcd2f,
  abstract     = {{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.}},
  author       = {{Sasiain, Inaki and Nacer, Deborah F. and Aine, Mattias and Veerla, Srinivas and Staaf, Johan}},
  issn         = {{2631-9268}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Oxford University Press}},
  series       = {{NAR Genomics and Bioinformatics}},
  title        = {{Tumor purity estimated from bulk DNA methylation can be used for adjusting beta values of individual samples to better reflect tumor biology}},
  url          = {{http://dx.doi.org/10.1093/nargab/lqae146}},
  doi          = {{10.1093/nargab/lqae146}},
  volume       = {{6}},
  year         = {{2024}},
}