Glyph: An Interpretability Engine for AI-Driven Scientific Discovery in Clinical Data

Abstract

Automated scientific discovery has the potential to advance understanding of disease mechanisms and accelerate identification of early disease markers. Manual data annotation is infeasible at population scale, motivating methods that automatically extract pre-defined phenotypes in multimodal and unstructured clinical data. Such pre-defined feature sets determine and limit which associations these approaches can discover. This limitation extends to agentic AI systems that use these tools to query population-scale data. In contrast, foundation models (FMs) trained on large volumes of clinical data can perform tasks beyond their training objectives. This suggests their latent embeddings may represent novel or unexplored features that could yield insights into disease mechanisms, yet such latent features remain difficult to interpret. To address this challenge, we introduce Glyph, an automated multistage framework that extracts features from multimodal and unstructured clinical data using FMs and sparse autoencoders, interprets them as coded clinical concepts, and evaluates their value for clinical scientific discovery. We applied Glyph to abdominal CT volumes, CT radiology reports and laboratory measurements from 41,628 patients across different institutions. We identified 397 predictive concepts supported by 4,463 Bonferroni-significant associations. Moreover, a majority of discovered associations were automatically reproducible in held-out cohorts across different sites. Glyph concepts provided complementary associations to literature-derived markers, leading to gains in predictive power. We envision that interpretability can extend beyond a mechanistic understanding of neural networks to connecting implicitly learned features with clinical knowledge and establishing their significance for patient outcomes. We release Glyph at https://github.com/StanfordMIMI/Glyph.