Patch the bias. Keep the biology.
normpatch is an R package for estimating normalization factors from bulk RNA-seq count data. It implements methods based on the DEGES framework, the DEG elimination strategy, which iteratively reduces the influence of DEGs when estimating sample-specific scaling factors. The framework is intended for datasets affected by compositional imbalance or strongly asymmetric DEG patterns, where standard normalization assumptions may not hold.
Sun J, Nishiyama T, Shimizu K, Kadota K. TCC: an R package for comparing tag count data with robust normalization strategies. BMC Bioinformatics. 14:219, 2013. 10.1186/1471-2105-14-219