Whole-blood transcriptomic traces of organ pathology and their causal triage

Researchers created a benchmark containing 59 pathologies across 20 organs in 803 donors with matched blood samples and postmortem histology. Using the TRACE framework, they identified which organ pathologies leave detectable traces in blood transcriptome while accounting for age, sex, and circumstances of death. Four pathologies passed testing, with liver cirrhosis being the strongest with an AUC score of 0.79. The cirrhosis signal was confirmed in an independent group of living patients with AUC 0.80 and remained specific to severe systemic illness. Using human genetics and Mendelian randomization, they identified causal factors including PAI-1, tenascin-C, and thrombospondin-2. The research provides a resource and methodology to determine which organ pathologies blood can detect and which signals are likely causal.