Serum is the most common and easily accessible patient specimen in a minimally invasive manner. As a biological resource, RNA in serum has been less explored for its clinical utilization due to prevailing concerns regarding its high degradable nature. In the current study, however, we have documented the use of human serum RNA for viral categorization and discovery through transcriptome sequencing and analysis using well-curated databases and advanced bioinformatic tools. Such an integrated approach may have an immediate application in any clinical situations concerning with viral etiology. (C) 2013 Elsevier Inc. All rights reserved.