Rapid advances in high-throughput sequencing technologies have led to the discovery of thousands of extrachromosomal circular DNAs (eccDNAs) in the human genome. Loss-of-function experiments are difficult to conduct on circular and linear chromosomes, as they usually overlap. Hence, it is challenging to interpret the molecular functions of eccDNAs. Here, we present CircleBase (http://circlebase.maolab.org), an integrated resource and analysis platform used to curate and interpret eccDNAs in multiple cell types. CircleBase identifies putative functional eccDNAs by incorporating sequencing datasets, computational predictions, and manual annotations. It classifies them into six sections including targeting genes, epigenetic regulations, regulatory elements, chromatin accessibility, chromatin interactions, and genetic variants. The eccDNA targeting and regulatory networks are displayed by informative visualization tools and then prioritized. Functional enrichment analyses revealed that the top-ranked cancer cell eccDNAs were enriched in oncogenic pathways such as the Ras and PI3K-Akt signaling pathways. In contrast, eccDNAs from healthy individuals were not significantly enriched. CircleBase provides a user-friendly interface for searching, browsing, and analyzing eccDNAs in various cell/tissue types. Thus, it is useful to screen for potential functional eccDNAs and interpret their molecular mechanisms in human cancers and other diseases.
