Metatranscriptomics to characterize respiratory virome, microbiome, and host response directly from clinical samples

• DOI: 10.1016/j.crmeth.2021.100091
• Publication Date: 2021-10-25T21:56:10Z
• Authors: Seesandra V. Raja...; Nicole G. Bakhoum; Suman B. Pakala; Meghan H. Shilts; Christian Rosas-S...; Annie Mai; Helen H. Boone; Rendie McHenry; Shibu Yooseph; Natasha Halasa; Suman R. Das
• Keywords: 0303 health sciences; 03 medical and health sciences; Virome; Respiratory Syncytial Virus, Human; Microbiota; Humans; Respiratory Syncytial Virus Infections; Child; Transcriptome; Article; 3. Good health

Abstract We developed a metatranscriptomics method that can simultaneously capture the respiratory virome, microbiome, and host response directly from low-biomass clinical samples. Using nasal swab samples, we have demonstrated that this method captures the comprehensive RNA virome with sufficient sequencing depth required to assemble complete genomes. We find a surprisingly high-frequency of Respiratory Syncytial Virus (RSV) and Coronavirus (CoV) in healthy children, and a high frequency of RSV-A and RSV-B co-infections in children with symptomatic RSV. In addition, we have characterized commensal and pathogenic bacteria, and fungi at the species-level. Functional analysis of bacterial transcripts revealed H. influenzae was highly active in symptomatic RSV subjects. Host transcriptome shows upregulation of the innate immune system, antiviral response and inflammasome pathway, and down regulation of fatty-acids pathway. This method is broadly applicable to infer transcriptome landscape of an infected system, surveil respiratory infections, and to sequence RNA viruses directly from clinical samples.