Decoding fibrosis: Transcriptomic and clinical insights via AI-derived collagen deposition phenotypes in MASLD
Marta Wojciechowska, Mira Thing, Yang Hu, Gianluca Mazzoni, Lea Mørch Harder, Mikkel Parsberg Werge, Nina Kimer, Vivek Das, Jaime Moreno Martinez, Cesar Prada-Medina, Mogens Vyberg, Robert Goldin, Reza Serizawa, Jeremy Tomlinson, Andreas Bartholdy, Majken Jensen, Elisabeth Douglas Galsgaard, Dan J. Woodcock, Henning Hvid, Dominik Reinhard Pfister, Vanessa Isabell Jurtz, Lise Lotte Gluud, Jens RittscherHistological assessment is foundational to multi-omics studies of liver disease, yet conventional fibrosis staging lacks resolution, and quantitative metrics like collagen proportionate area (CPA) fail to capture tissue architecture. While recent AI-driven approaches offer improved precision, they are proprietary and not accessible to academic research. Here, we present a novel, interpretable AI-based framework for characterising liver fibrosis from picrosirius red (PSR)-stained slides. By identifying distinct data-driven collagen deposition phenotypes (CDPs) which capture distinct morphologies, our method substantially improves the sensitivity and biological specificity of downstream transcriptomic and proteomic analyses compared to CPA and traditional fibrosis scores. Pathway analysis reveals that CDPs 4 and 5 are associated with active extracellular matrix remodelling, while phenotype correlates highlight links to liver functional status. Importantly, selected CDPs demonstrated prognostic associations in the discovery cohort, with attenuation of discrimination in the external validation cohort. All models and tools are made freely available to support transparent and reproducible multi-omics pathology research.