Currently, the majority of circulating tumour DNA (ctDNA) fragmentomic techniques lack the ability to achieve gene-level resolution and are effective mainly in inferring expression at elevated ctDNA levels. Consequently, they are primarily applicable to patients with notably advanced tumour burdens typically seen in late-stage cancer.
To address this limitation, EPIC-seq employs hybrid capture-based targeted deep sequencing of regions flanking transcription start sites (TSS) in cfDNA. This approach allows for the acquisition of ctDNA fragmentation features crucial for predicting gene expressions, such as Promoter Fragmentation Entropy (PFE) and Nucleosome Depleted Region (NDR). These key fragmentomic features possess the capability to capture associations at the gene level with expression levels throughout the genome, enabling the construction of a predictive model for transcriptional output. This would allows for the high-resolution monitoring of cfDNA fragmentation and gene-level analysis.