Fig. 2

Differential transcript masking. Dynamics among transcripts may not be detected with gene-level analyses due to cancellation (a), domination (b), and collapsing (c). Gene counts and constituent transcript counts are plotted between conditions (dexamethasone vs vehicle treatment) and annotated with Ensembl ID and sleuth-derived p values. In the case of cancellation (a), the abundance of transcripts changing in opposite directions cancels out upon conversion to gene abundance. In domination (b), an abundant transcript that is not changing can mask substantial change in abundance of a minor transcript. In the case of collapsing (c), multiple isoforms of a gene with small effect sizes in the same direction do not lead to a significant change when observed after summation, but their independent changes constitute substantial evidence for differential expression. In all these examples, gene-level differential analysis with sleuth failed to identify the genes as differential (p values listed on x-axis), whereas Lancaster aggregation of transcript p values resulted in detection of the genes as differential