Genes are defined as biologically meaningful if they pass cut-offs for effect size (log fold change) and statistical significance. These cut-offs should ideally be specified a priori, but the nature of RNA-Seq experiments is often exploratory so it is difficult to predict effect sizes and pertinent cut-offs ahead of time. Pitfalls: The raison d'etre for these complex methods is to avoid the myriad of pitfalls that can lead to statistical errors and misleading interpretations.