Supernatants were treated with Proteinase K (Jena, 845-CH-0010030, stock concentration 22 mg/mL) for 1 hour or overnight at 37°C at 8.3 µl per 100 µl medium, and purified with the DNA Clean & Concentrator Kit (Zymo, D4004) mixing SN with DNA binding buffer at ratio 1:5. Genomic DNA was isolated with the PureLink Genomic DNA kit (Invitrogen,  K182001) according to manufacturer's instructions. gDNA, but not cfDNA, was fragmented using a Covaris S2 system (intensity:10, duty cycle: 5%, cycles per burst: 200, duration: 90 seconds), cleaned up with the DNA Clean and Concentrator-5 kit (Zymo, D4004), quantified and quality-controlled on a TapeStation device as described above, and 100 ng of sheared reference genomic DNA and 48 ng of cell-free DNA were bisulfite converted using the EZ DNA Methylation-Gold kit (Zymo, D5005), eluting in lowEDTA TE buffer, pH 8.0 (IDT11-05-01-13). WGBS libraries were prepared with the xGen™ Methyl-Seq DNA Library Prep Kit (IDT, 10009824), at 8 indexing PCR cycles with the xGEN UDIPrimer Plate 2, 8nt (IDT, 10009816), and sequenced as 150-bp paired-end reads on an Illumina NovaSeq 6000 system.