Researchers at Peking University unveiled cf‑EpiTracing, an automated cell‑free DNA approach that profiles chromatin marks to infer tissue and cell‑type origins of disease from plasma. Published in Nature, the method uses histone‑modification immunocapture followed by Tn5 tagmentation and sequencing to generate integrated chromatin state (ICS) signatures that can distinguish affected organs across cancer, coronary heart disease, lymphoma and IBD. The team distilled a minimal set of histone marks—H3K9ac, H3K27ac and H3K4me3—that preserved predictive accuracy and applied cf‑EpiTracing to more than 2,400 plasma profiles to report tissue contributions and disease‑specific signatures. The method complements transcription‑centric cfDNA assays by focusing on epigenetic packaging rather than gene expression alone. cf‑EpiTracing could expand noninvasive molecular diagnostics and disease monitoring by revealing tissue involvement and therapeutic response signals without invasive biopsies. The automated and epigenome‑centric workflow positions the approach for larger cohort studies and potential clinical translation.