Comprehensive analysis of circulating viral DNA in maternal plasma at population-scale using low-pass whole-genome sequencing

As the most readily adopted molecular screening test, low-pass WGS of maternal plasma cell-free DNA for aneuploidy detection generates a vast amount of genomic data. This large-scale method also allows for high-throughput virome screening. NIPT sequencing data, yielding 6.57 terabases of data from 187.8 billion reads, from 12,951 pregnant Turkish women was used to investigate the prevalence and abundance of viral DNA in plasma. Among the 22 virus sequences identified in 12% of participants were human papillomavirus, herpesvirus, betaherpesvirus and anellovirus. We observed a unique pattern of circulating viral DNA with a high prevalence of papillomaviruses. The prevalence of herpesviruses/anellovirus was similar among Turkish, European and Dutch populations. Hepatitis B prevalence was remarkably low in Dutch, European and Turkish populations, but higher in China. WGS data revealed that herpesvirus/anelloviruses are naturally found in European populations. This represents the first comprehensive research on the plasma virome of pregnant Turkish women.