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Cell-type heterogeneity: Why we should adjust for it in epigenome and biomarker studies.

Luo QiAndrew E Teschendorff
Published in: Clinical epigenetics (2022)
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.
Keyphrases
  • single cell
  • dna methylation
  • gene expression
  • stem cells
  • induced apoptosis
  • cell therapy
  • case control
  • high resolution
  • cell death
  • mass spectrometry
  • heat stress