To establish that bulk NAT serves as a reliable reference regardless of tumor subtype, we freshly isolated alveolar type 2 (AT2) cells, the cell of origin of LUAD, and basal cells (BSC), the cell of origin of LUSC, from bulk NAT from five TRACERx samples (Extended Data Fig. 2a); no significant differences were found in the methylation β values compared to bulk NAT (Extended Data Fig. 2b). Here, BRD2 is linked to neoplasm.