With the advancement of the sequencing technology, the investigation into functions for transcriptomes from non-model organisms is increasingly demanded. However, most tools in this field are designed for GO and KEGG analyses with support limited to one or several model organisms. Besides, there are increasingly more biological knowledge databases available for exploring functional characteristics from different perspectives, such as Disease Ontology,24 Reactome Pathway,25 Medical Subject Headings,26, and WikiPathway.27 There is an urgent need for integration and support of these databases. To address these issues, clusterProfiler provides two general functions, enricher and GSEA for ORA and GSEA, with user-provided gene annotations. These two functions allow the application of all ontologies or pathways curated in diverse databases as the background in customized analyses. Therefore, users could easily import external annotations (e.g., electronic annotations using Blast2GO28 and KAAS29 for GO and KEGG annotations, respectively) for newly sequenced species. Moreover, it is convenient to perform functional analysis using up-to-date annotations from all popular databases, such as InterPro, Clusters of Orthologous Groups, and Mouse Phenotype Ontology, to name a few, without waiting for the updates