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Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling.

ABSTRACT: DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used to identify libraries for deconvolution of DNA methylation data for current and previous platforms. The accuracy of deconvolution estimates obtained using our enhanced libraries was validated using artificial mixtures and whole-blood DNA methylation with known cellular composition from flow cytometry. We applied our libraries to deconvolve cancer, aging, and autoimmune disease datasets. In conclusion, these libraries enable a detailed representation of immune-cell profiles in blood using only DNA and facilitate a standardized, thorough investigation of immune profiles in human health and disease.

SUBMITTER: Salas LA

PROVIDER: S-EPMC8828780 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling.

Salas Lucas A LA Zhang Ze Z Koestler Devin C DC Butler Rondi A RA Hansen Helen M HM Molinaro Annette M AM Wiencke John K JK Kelsey Karl T KT Christensen Brock C BC

Nature communications 20220209 1

DNA methylation microarrays can be employed to interrogate cell-type composition in complex tissues. Here, we expand reference-based deconvolution of blood DNA methylation to include 12 leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, naïve and memory B cells, naïve and memory CD4 + and CD8 + T cells, natural killer, and T regulatory cells). Including derived variables, our method provides 56 immune profile variables. The IDOL (IDentifying Optimal Libraries) algorithm was used ...[more]

PMID: 35140201

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Project description:BackgroundIrritable bowel syndrome (IBS) is a stress-sensitive disorder. Environmental factors including stress can trigger epigenetic changes, which have not been well-studied in IBS. We performed a pilot study investigating genome-wide DNA methylation of IBS patients and healthy controls (HCs) to identify potential epigenetic markers and associated pathways. Additionally, we investigated relationships of epigenetic changes in selected genes with clinical traits.MethodsTwenty-seven IBS patients (59% women; 10 IBS-diarrhea, 8 IBS-constipation, 9 IBS-mixed) and 23 age- and sex-matched HCs were examined. DNA methylation from peripheral blood mononuclear cells (PBMCs) was measured using HM450 BeadChip, and representative methylation differences were confirmed by bisulphite sequencing. Gene expression was measured using quantitative PCR. Gastrointestinal (GI) and non-GI symptoms were measured using validated questionnaires. Associations were tested using non-parametric methods.Key resultsGenome-wide DNA methylation profiling of IBS patients compared with HCs identified 133 differentially methylated positions (DMPs) (mean difference ≥10%; p < 0.05). These genes were associated with gene ontology terms including glutathione metabolism related to oxidative stress and neuropeptide hormone activity. Validation by sequencing confirmed differential methylation of subcommissural organ (SCO)-Spondin (SSPO), glutathione-S-transferases mu 5 (GSTM5), and tubulin polymerization promoting protein genes. Methylation of two promoter CpGs in GSTM5 was associated with epigenetic silencing. Epigenetic changes in SSPO gene were positively correlated with hospital anxiety and depression scores in IBS patients (r > 0.4 and false discovery rate <0.05).Conclusions & inferencesThis study is the first to comprehensively explore the methylome of IBS patients. We identified DMPs in novel candidate genes which could provide new insights into disease mechanisms; however, these preliminary findings warrant confirmation in larger, independent studies.

Dataset Information

Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling.

Publications

Enhanced cell deconvolution of peripheral blood using DNA methylation for high-resolution immune profiling.

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