查看文章

Data normalization is an essential step to reduce technical variation within and between arrays. Due to the different karyotypes and the effects of X chromosome inactivation, females and males exhibit distinct methylation patterns on sex chromosomes; thus, it poses a significant challenge to normalize sex chromosome data without introducing bias. Currently, existing methods do not provide unbiased solutions to normalize sex chromosome data, usually, they just process autosomal and sex chromosomes indiscriminately.

Here, we demonstrate that ignoring this sex difference will lead to introducing artificial sex bias, especially for thousands of autosomal CpGs. We present a novel two-step strategy (interpolatedXY) to address this issue, which is applicable to all quantile-based normalization methods. By this new strategy, the autosomal CpGs are first …