Cell-type-specific damage scores reveal kidney and liver disease trajectories in single-cell and spatial transcriptomics.

Cell-type-specific damage scores accurately identify disease progression in kidney and liver diseases across multiple datasets, with PDS and HDS revealing damage thresholds and pathways.

• Why it matters: Understanding gradual cell-intrinsic damage in degenerative diseases is challenging with traditional bulk or discrete cell-state analyses, limiting insights into disease trajectories and therapeutic targets.
• What they did: The study developed a generalizable framework using single-cell and spatial transcriptomics to quantify continuous damage scores, applied to chronic kidney disease and MASLD/NASH, involving over 100 datasets including scRNA-seq, snRNA-seq, proteomics, histology, and clinical data.
• The result: Damage scores robustly detect disease-associated damage, identify conserved pathways, and reveal damage thresholds, enabling scalable mapping of disease progression and stage-specific therapeutic strategies.