Transcriptome- and DNA methylation-based cell-type deconvolutions produce similar estimates of differential gene expression and differential methylation

Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expres...

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Bibliographic Details
Published in:BioData mining 2024-07, Vol.17 (1), p.21-16, Article 21
Main Authors: Hannon, Emily R, Marsit, Carmen J, Dent, Arlene E, Embury, Paula, Ogolla, Sidney, Midem, David, Williams, Scott M, Kazura, James W
Format: Article
Language:English
Subjects:
Analysis
B cells
Deconvolution
Deoxyribonucleic acid
DNA
DNA methylation
Epigenetics
Estimates
Flow cytometry
Gene expression
Genes
Genomes
Genomics
Leukocytes (mononuclear)
Leukocytes (neutrophilic)
Lymphocytes
Malaria
Methylation
PBMC
Peripheral blood mononuclear cells
Ribonucleic acid
RNA
Transcriptomes
Transcriptomics
Vector-borne diseases
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Summary:Changing cell-type proportions can confound studies of differential gene expression or DNA methylation (DNAm) from peripheral blood mononuclear cells (PBMCs). We examined how cell-type proportions derived from the transcriptome versus the methylome (DNAm) influence estimates of differentially expressed genes (DEGs) and differentially methylated positions (DMPs). Transcriptome and DNAm data were obtained from PBMC RNA and DNA of Kenyan children (n = 8) before, during, and 6 weeks following uncomplicated malaria. DEGs and DMPs between time points were detected using cell-type adjusted modeling with Cibersortx or IDOL, respectively. Most major cell types and principal components had moderate to high correlation between the two deconvolution methods (r = 0.60-0.96). Estimates of cell-type proportions and DEGs or DMPs were largely unaffected by the method, with the greatest discrepancy in the estimation of neutrophils. Variation in cell-type proportions is captured similarly by both transcriptomic and methylome deconvolution methods for most major cell types.
ISSN:1756-0381
1756-0381
DOI:10.1186/s13040-024-00374-0