Autonomous Spatial Transcriptomics Analysis (ASTA): Demonstrating Performance Improvements through Clustering, Biological Annotation, and AI-Driven Discovery

Abstract

Spatial transcriptomics keeps measurement of gene expression while preserving spatial context, yet traditional analysis methods face challenges in computational efficiency, biological interpretability, and autonomous discovery. This project presents a framework solving these issues through three parts: (1) an ensemble clustering system achieving 66.7% improvement over baseline average and 23.9% over best single method with silhouette score of 0.540 and statistical significance (p = 0.0032, Cohens d = 1.82); (2) a knowledge-based clustering framework that annotates 88.6% of cells across 8 ovarian cell types using 428 marker genes; and (3) a GPT-4o-mini-powered autonomous agent that generated 3 biological hypotheses with validations.