Actively expressed genes have open chromatin at their TSS region, they are less shielded by nucleosomes and, therefore, more susceptible to endonuclease cleavage. Consequently, the depth of cfDNA originating from the TSS of active genes tends to be shallower compared to that of inactive genes.  NDR quantifies the normalized depth within each 2-kilobase window surrounding each TSS. The lower the NDR of a gene TSS site, the more likely the gene is highly expressed.