CASCADE: An Agentic Regulatory Network Framework for Patient-Data-Validated Downstream Perturbation Prediction

arXiv cs.AIAugust 7, 2026en

arXiv:2608.05359v1 Announce Type: new Abstract: CASCADE is an agentic framework that predicts downstream transcriptional effects of gene perturbation from precomputed ARACNe regulatory networks, exposed via MCP. Prior work validates such tools by checking whether predicted genes are known cancer genes (membership); we instead test whether the predicted direction of change matches reality, using focal-gene copy-number amplification as a dosage-based proxy for the inverse of knockdown against real TCGA patient tumor data. For MYC, CASCADE's predicted knockdown targets show strong concordance with real amplified-vs-non-amplified tumor expression across three cancer types (BRCA: 90.0%, COAD: 72.

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