Data from: Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies
Hattab, Mohammad W. et al. (2018), Data from: Correcting for cell-type effects in DNA methylation studies: reference-based method outperforms latent variable approaches in empirical studies, Dryad, Dataset, https://doi.org/10.5061/dryad.bv376
Based on an extensive simulation study, McGregor and colleagues recently recommended the use of surrogate variable analysis (SVA) to control for the confounding effects of cell-type heterogeneity in DNA methylation association studies in scenarios where no cell-type proportions are available. As their recommendation was mainly based on simulated data, we sought to replicate findings in two large-scale empirical studies. In our empirical data, SVA did not fully correct for cell-type effects, its performance was somewhat unstable, and it carried a risk of missing true signals caused by removing variation that might be linked to actual disease processes. By contrast, a reference-based correction method performed well and did not show these limitations. A disadvantage of this approach is that if reference methylomes are not (publicly) available, they will need to be generated once for a small set of samples. However, given the notable risk we observed for cell-type confounding, we argue that, to avoid introducing false-positive findings into the literature, it could be well worth making this investment.