Year: 2021
Type: conference-abstract
Abstract: Background: The microbiome has a role in human diseases and overall health outcomes. Taxonomic profiles of many body sites are highly personalized, though many species are shared. Through use of RNA and DNA sequencing that detect viral nucleic acids, evidence has emerged regarding a healthy human blood virome. This study of the blood virome in a population of current and former smokers with and without chronic obstructive pulmonary disease (COPD) may help to inform future individualized treatment by revealing links between the viral taxa and complex disease. Methods: We detected viral ribonucleic acids in peripheral blood RNA-sequencing from 3,984 current and former smokers with and without COPD from the COPDGene study. We detected the viral signature in the RNA-sequencing reads not mapped to the human genome during the primary analysis using PathSeq, a pipeline in the Genome Analysis Toolkit (GATK). This pipeline provided additional cleaning of the reads and subsequent mapping to viral genomes. We tested associations between the inferred viral abundance profiles and pulmonary phenotypes and examined links to host gene expression pathways. Results: Among the 3,984 subjects with RNA-seq data passing quality control, 1,601 were COPD cases (GOLD 1-4) and 1,609 were controls. Also included were 206 never-smokers. We detected HIV nucleic acids in 30 subjects and Hepatitis C in 228 subjects, highlighting public health implications for this study. Of the 30 subjects with detectable levels of HIV, 22 self-reported HIV infections. We observed associations between inferred abundance of Hepatitis C and both neutrophil (q-value < 0.0001) and lymphocyte (q = 0.0017) percentage. Hepatitis C (q = 0.003) and Epstein-Barr virus (q = 0.038) were associated with current smoking status. A nominal association (p = 0.002, q = 0.54) was found for Cytomegalovirus and a history of a severe exacerbation in the prior year. We integrated the virome profiles with host gene expression and observed associations (q < 0.05) between four viral taxa and human interferon pathways. Conclusions: This study is the first to identify the virome in the peripheral blood of a COPD-enriched population of current and former smokers. We observed associations between viral profiles in peripheral blood and host clinical data. Through integration with host gene expression, we linked detected viral taxa with host interferon pathways. Understanding the relationships between the systemic viral populations and complex disease may inform novel interventions and aid in the understanding of exacerbation phenotypes.
Authors: J. Morrow, P. Castaldi, R. Chase, J.H. Yun, S. Lee, Y.-Y. Liu, E.K. Silverman, C.P. Hersh, COPDGene Investigators
Institution: Brigham and Women's Hospital
Language: English
Subfield: Ecology
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Awards: G2417563097, INTEGRATIVE GENOMICS OF CLINICAL SUBTYPES IN COPDGENE, Prospective Health Outcomes and Inflammatory Biomarkers Associated with e-Cigarette Use, (2 of 2) Genetic Epidemiology of COPD, Using Integrative Genomics To Identify and Characterize Emphysema-Associated eQTL, (1 of 2) Genetic Epidemiology of COPD, SYSTEMS GENOMICS OF THE ASTHMA-COPD OVERLAP SYNDROME, Integrative omics pipeline to identify novel COPD genes and pathways, G993448119
OpenAlex ID: W4253904871