ArticleClinical epigenetics2022
Cell-type heterogeneity: Why we should adjust for it in epigenome and biomarker studies.
Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A systematic review of methylome-wide associations with anxiety disorders.Translational psychiatry · 2026Pooled it
- Brain-derived neurotrophic factor (BDNF) epigenomic modifications and brain-related phenotypes in humans: A systematic review.Neuroscience and biobehavioral reviews · 2023Pooled it
- Strong concordance of DNA methylation measures between venous and capillary blood - Implications for human epigenome studies.iScience · 2026Article
- The Evolving Landscape of Clinical Aging Clocks: From Epigenetic to Multi-Omics Integration.Aging cell · 2026Review
- Epigenome-Wide DNA Methylation Levels During Pregnancy: Associations with Parity Across Diverse Populations.Epigenomes · 2026Article
- The association of epigenetic age acceleration with internal smoking dose, risk of lung cancer, and all-cause mortality in cigarette smokers: the Multiethnic Cohort study.Clinical epigenetics · 2026Article
- Tracing cell communication programs across conditions at single cell resolution with CCC-RISE.bioRxiv : the preprint server for biology · 2026Article
- Guidelines on optimizing DNA methylation reference panels for cell-type deconvolution.Communications biology · 2026Article
- Sex-specific nonlinear DNA methylation aging trajectories reveal biomarkers of cancer risk and inflammation.Genome biology · 2026Article
- Not all saliva samples are equal: The role of cellular heterogeneity in DNA methylation and epigenetic age analyses with biological and psychosocial factors.Psychoneuroendocrinology · 2026Article
- Integrative Analysis of Placental Methylomes Identifies Epigenetically Regulated Genes Implicated in Fetal Growth Restriction.International journal of molecular sciences · 2026Article
- Cord blood DNA methylation and cell-type composition are not significantly associated with severe preeclampsia after cell-type and clinical covariate adjustment.GigaScience · 2026Article
- Complement as a driver of immune-vascular heterogeneity across preeclampsia subtypes: toward a precision medicine framework.Frontiers in immunology · 2026Review
- Relationship stress and epigenetic age acceleration among older U.S. adults in the Midlife in the United States study.Epigenomics · 2025Article
- Using Multi-Omic Signatures in the Understanding of Inflammation and Psychosis: Can Methylation-Derived White Blood Cell Proportions Guide Early Intervention?Biological psychiatry global open science · 2025Article
- Proteomic Insight Into Alzheimer's Disease Pathogenesis Pathways.Proteomics · 2025Review
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- Distinct maternal DNA methylation associations with gestational age at early and late-mid term pregnancy in a low- and middle-income country: evaluation of biological, genetic, and psychosocial contributors.BMC pregnancy and childbirth · 2025Article
- Brain region and cell type-specific DNA methylation profiles in association with ADHD.Scientific reports · 2025Article
- Beyond genes: a clinician's guide to epigenetics.Breathe (Sheffield, England) · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Most studies aiming to identify epigenetic biomarkers do so from complex tissues that are composed of many different cell-types. By definition, these cell-types vary substantially in terms of their epigenetic profiles. This cell-type specific variation among healthy cells is completely independent of the variation associated with disease, yet it dominates the epigenetic variability landscape. While cell-type composition of tissues can change in disease and this may provide accurate and reproducible biomarkers, not adjusting for the underlying cell-type heterogeneity may seriously limit the sensitivity and precision to detect disease-relevant biomarkers or hamper our understanding of such biomarkers. Given that computational and experimental tools for tackling cell-type heterogeneity are available, we here stress that future epigenetic biomarker studies should aim to provide estimates of underlying cell-type fractions for all samples in the study, and to identify biomarkers before and after adjustment for cell-type heterogeneity, in order to obtain a more complete and unbiased picture of the biomarker-landscape. This is critical, not only to improve reproducibility and for the eventual clinical application of such biomarkers, but importantly, to also improve our molecular understanding of disease itself.
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Registered trials
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