severely underestimated, with only 26% of biological processes or pathways captured in comparison with those employing up-to-date annotation. Such negative impacts of outdated annotation can be propagated for years and can hinder follow-up studies. Reanalyzing the GTEx dataset6 published by the ENCODE consortium using clusterProfiler uncovered a large number of new pathways, which were missed in the analysis using out-of-date annotation (https://github.com/GuangchuangYu/enrichment4GTEx_clusterProfiler), and new hypotheses were generated based on these new pathways.