Abstract
We introduce RegNetAgents, an AI-oriented multi-agent framework for structured, query-driven regulatory candidate identification across heterogeneous gene regulatory networks. The system enables unified analysis of bulk tumor and single-cell-derived ARACNe networks by integrating TCGA-derived cancer networks with large-scale single-cell regulatory networks from the GREmLN project.
For a given focal gene, the framework performs dual-network classification, cancer gene filtering using OncoKB annotations, and mode-of-action (MoA) assignment for tumor-derived regulatory relationships. Candidates are ranked by evidence consistency across networks (Both, TCGA-only, GREmLN-only). The system is implemented as a multi-agent LangGraph DAG workflow, accessible through a unified Python API and Model Context Protocol (MCP) client, operating as a downstream analytical layer over precomputed regulatory networks rather than a network inference method.
Across eleven breast cancer (BRCA) and twelve colorectal cancer (COAD) focal genes, RegNetAgents identifies candidate regulators significantly enriched for OncoKB-annotated cancer genes. TCGA-derived candidates show strong enrichment (Stouffer Z = 6.69 for BRCA and 6.95 for COAD), while GREmLN-derived candidates also demonstrate significant enrichment (Z = 5.51 for BRCA and 7.06 for COAD; all p < 0.05).
Blogger's Review: RegNetAgents offers a robust tool for cross-network regulatory candidate identification through a multi-agent framework. This approach not only enhances the efficiency of cancer genomics research but also provides new insights for future personalized medicine. Its integration analysis of TCGA and GREmLN data showcases significant clinical potential, making it a noteworthy development.