SAGE: Agentic Framework for Interpretable and Clinically Translatable Computational Pathology Biomarker Discovery

Despite significant progress in computational pathology, many AI models remain black-box and difficult to interpret, posing a major barrier to clinical adoption due to limited transparency and explainability. This has motivated continued interest in engineered image-based biomarkers, which offer greater interpretability but are often proposed based on anecdotal evidence or fragmented prior literature rather than systematic biological validation. We introduce SAGE (Structured Agentic system for hypothesis Generation and Evaluation), an agentic AI system designed to identify interpretable, engineered pathology biomarkers by grounding them in biological evidence. SAGE integrates literature-anchored reasoning with multimodal data analysis to correlate image-derived features with molecular biomarkers, such as gene expression, and clinically relevant outcomes. By coordinating specialized agents for biological contextualization and empirical hypothesis validation, SAGE prioritizes transparent, biologically supported biomarkers and advances the clinical translation of computational pathology.

Rethinking Bias in Generative Data Augmentation for Medical AI: a Frequency Recalibration Method

Developing Medical AI relies on large datasets and easily suffers from data scarcity. Generative data augmentation (GDA) using AI generative models offers a solution to synthesize realistic medical images. However, the bias in GDA is often underestimated in medical domains, with concerns about the risk of introducing detrimental features generated by AI and harming downstream tasks. This paper identifies the frequency misalignment between real and synthesized images as one of the key factors underlying unreliable GDA and proposes the Frequency Recalibration (FreRec) method to reduce the frequency distributional discrepancy and thus improve GDA. FreRec involves (1) Statistical High-frequency Replacement (SHR) to roughly align high-frequency components and (2) Reconstructive High-frequency Mapping (RHM) to enhance image quality and reconstruct high-frequency details. Extensive experiments were conducted in various medical datasets, including brain MRIs, chest X-rays, and fundus images. The results show that FreRec significantly improves downstream medical image classification performance compared to uncalibrated AI-synthesized samples. FreRec is a standalone post-processing step that is compatible with any generative model and can integrate seamlessly with common medical GDA pipelines.