Protocol for profiling chromatin accessibility in human small-cell lung cancer FFPE-derived samples using Omni-ATAC-seq.

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) on formalin-fixed paraffin-embedded (FFPE) samples maps accessible chromatin in archival tissues, but DNA degradation and crosslinking remain significant challenges when processing these samples. Here, we present a protocol for Omni-ATAC-seq on degraded human small-cell lung cancer (SCLC) FFPE-derived samples. We detail steps for successful nuclei isolation, efficient tagmentation, and optimal library amplification to overcome the low signal-to-noise ratio. This protocol enables high-quality epigenetic profiling, turning archived SCLC samples into valuable resources for studying disease progression. For complete details on the use and execution of this protocol, please refer to Kawasaki et al.1.