RT Journal Article
SR Electronic
T1 Correcting for cell-type heterogeneity in epigenome-wide association studies: premature analyses and conclusions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 121533
DO 10.1101/121533
A1 Shijie C Zheng
A1 Stephan Beck
A1 Andrew E. Jaffe
A1 Devin C. Koestler
A1 Kasper D. Hansen
A1 Andres E. Houseman
A1 Rafael A. Irizarry
A1 Martin Widschwendter
A1 Andrew E. Teschendorff
YR 2017
UL http://biorxiv.org/content/early/2017/03/28/121533.abstract
AB Recently, a study by Rahmani et al [1] claimed that a reference-free cell-type deconvolution method, called ReFACTor, leads to improved power and improved estimates of cell-type composition compared to competing reference-free and reference-based methods in the context of Epigenome-Wide Association Studies (EWAS). However, we identified many critical flaws (both conceptual and statistical in nature), which seriously question the validity of their claims. We outlined constructive criticism in a recent correspondence letter, Zheng et al [2]. The purpose of this letter is two-fold. First, to present additional analyses, which demonstrate that our original criticism is statistically sound. Second, to highlight additional serious concerns, which Rahmani et al have not yet addressed. In summary, we find that ReFACTor has not been demonstrated to outperform state-of-the-art reference-free methods such as SVA or RefFreeEWAS, nor state-of-the-art reference-based methods. Thus, the claim by Rahmani et al (a claim reiterated in their recent response letter [3]) that ReFACT or represents an advance over the state-of-the-art is not supported by an objective and rigorous statistical analysis of the data.