CircleBase

CircleBase provides an integrated resource for the curation and analysis of extrachromosomal circular DNAs (eccDNAs) in the human genome.

Key Features:

• Integration of sequencing datasets: Incorporates high-throughput sequencing datasets for curation and analysis of eccDNAs.
• Computational predictions and manual annotations: Combines computational predictions with manual annotations to identify putative functional eccDNAs.
• Classification scheme: Systematically classifies eccDNAs into six categories: targeting genes, epigenetic regulations, regulatory elements, chromatin accessibility, chromatin interactions, and genetic variants.
• Regulatory-network visualization: Visualizes eccDNA targeting and regulatory networks through graphical representations.
• Prioritization of candidate eccDNAs: Enables prioritization of eccDNAs based on predicted functional significance.
• Functional enrichment analysis: Performs functional enrichment analyses indicating enrichment of eccDNAs in oncogenic pathways such as Ras and PI3K-Akt in cancer cells.
• Cross–cell/tissue analysis: Supports analysis and comparison of eccDNA features across various cell and tissue types, including healthy and cancer samples.

Scientific Applications:

• Screening for functional eccDNAs: Identification and prioritization of putative functional eccDNAs for experimental follow-up.
• Oncogenesis research: Investigation of eccDNA contributions to cancer-related pathways, including Ras and PI3K-Akt signaling enrichment in cancer cells.
• Comparative studies: Comparative analysis of eccDNA landscapes between healthy and diseased (cancer) tissues or cell types.
• Mechanistic interpretation: Interpretation of eccDNA-associated regulatory mechanisms via integration of epigenetic, chromatin accessibility, interaction, and variant information.

Methodology:

CircleBase integrates high-throughput sequencing datasets, computational predictions, and manual annotations to classify eccDNAs into six categories (targeting genes; epigenetic regulations; regulatory elements; chromatin accessibility; chromatin interactions; genetic variants), performs functional enrichment analyses, and visualizes eccDNA targeting and regulatory networks.