Biosecurity-Aware AI: Agentic Risk Auditing of Soft Prompt Attacks on ESM-Based Variant Predictors

Huixin Zhan

Keywords: Genomic foundation models, soft prompt attack, adversarial robustness

TL;DR: We introduce SAGE, an agentic auditing framework that detects adversarial vulnerabilities in Genomic Foundation Models (GFMs) like ESM.

Abstract: Genomic Foundation Models (GFMs), such as Evolutionary Scale Modeling (ESM), have demonstrated remarkable success in variant effect prediction. However, their security and robustness under adversarial manipulation remain largely unexplored. To address this gap, we introduce the Secure Agentic Genomic Evaluator (SAGE), an agentic framework for auditing the adversarial vulnerabilities of GFMs. SAGE functions through an interpretable and automated risk auditing loop. It injects soft prompt perturbations, monitors model behavior across training checkpoints, computes risk metrics such as AUROC and AUPR, and generates structured reports with large language model-based narrative explanations. This agentic process enables continuous evaluation of embedding-space robustness without modifying the underlying model. Using SAGE, we find that even state-of-the-art GFMs like ESM2 are sensitive to targeted soft prompt attacks, resulting in measurable performance degradation. These findings reveal critical and previously hidden vulnerabilities in genomic foundation models, showing the importance of agentic risk auditing in securing biomedical applications such as clinical variant interpretation.

Submission Number: 26