Wide-spectrum profiling of plasma cell-free RNA and the potential for health-monitoring

Circulating cell-free RNA (cfRNA) has emerged as a promising analyte for disease detection. However, the comprehensive profiling of diverse cfRNA types remains under-characterized. Here, we applied a new wide-spectrum cfRNA sequencing method and simultaneously captured rRNA, tRNA, mRNA, miRNA, lncRNA and all mitochondrial RNA. The cfRNA compositions, size distributions and highly abundant cfRNA genes were analysed for each type of cfRNA. We depicted the cfRNA cell types of origin profiles of 66 generally healthy individuals and found that BMI showed a significant impact on the kidney-derived cfRNA proportion. Three individuals with some liver problems were identified because of relatively high levels of hepatocyte-specific cfRNA. The abundance levels of different genes and RNA types, including mRNA, miRNA and lncRNA, were significantly correlated with the liver function test results. The genes of individual cfRNA variances were enriched in pathways associated with common diseases such as liver diseases, virus infections, cancers and metabolic diseases. This study provided a profiling of cfRNA and displayed the potential of cfRNA as a biomarker in health monitoring.