Functional enrichment analysis is one of the most widely used techniques for interpreting gene lists or genome-wide regions of interest (ROIs)1 derived from various high-throughput studies. Although many tools have been developed for gene-centric or epigenomic enrichment analysis, most are designed for model organisms or specific domains (e.g., fungi,2 plants3) embedded with particular annotations such as Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG).4 Non-model organisms and functional annotations other than GO and KEGG are poorly supported. Moreover, the increasing concerns for the quality of gene annotation have raised an alarm in biomedical research. Because annotation databases have diverse or irregular update periods, many tools may fail to update the corresponding information in time. A previous study5 reported that about 42% of the tools were outdated by more than 5 years and that functional significance was severely underestimated, with only 26% of biological processes or pathways captured in comparison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 Such negative impacts of outdated annotation can be propagated for years and can hinder follow-up studies.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
