Both approaches performed comparably to historical comparisons with NfL and GFAP (AUC 0.77 each) in a subset of the same cohort, suggesting that cfDNA methylation and its inferred tissue-of-origin had the potential to predict MS disease severity at blood collection, though further confirmation is required given the less robust predictive performance when attempting to predict PDDS≥4 vs <4 using the current dataset (with or without confounder adjustment), possibly due to the modest sample size limiting statistical power (data not shown). The gene discussed is NEFL; the disease is myeloid sarcoma.