A comprehensive collection of systems biology data characterizing the host response to viral infection

Abstract

The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). By comparing data from mutant versus wild-type virus and host strains, RNA versus protein differential expression, and infection with genetically similar strains, these data can be used to further investigate genetic and physiological determinants of host responses to viral infection.

Figure 1. Overall study design for the study of the systems biology of viral infection.

The ovals down the center represent steps in the experimental workflow common to all datasets. Text on the left gives the type of metadata required to describe the components of the workflow. On the right lists the experiment conditions investigated at each step throughout these datasets.

Figure 2. Computational validation of results.

(a) Shows the comparison performed between all significant host factors identified by transcriptomics in the ICL006-R and ICL010-R experiments, both of which involved infection of Calu-3 cells with A/California/04/2009 at 3 multiplicity of infection (MOI). (b) Compares all significant host factors identified by transcriptomics in the ICL004-R, ICL011-R and ICL012-R experiments, which involved infection of Calu-3 cells with the A/Viet Nam/1203/2004 strain at 1 MOI. (c) A comparison between all significant host factors identified by transcriptomics in the CA04M001-R and IM009-R experiments, both of which involved infection of C57BL/6 mice with 10⁶ plaque forming units (PFU) of A/California/04/2009. (d) Compares all significant host factors identified by transcriptomics in the IM001-R and IM010-R experiments, both of which involved infection of C57BL/6 mice with 10³ PFU of A/Viet Nam/1203/2004. (e) Compares all significant host factors identified by transcriptomics in the SHAE002-R and SHAE003-R experiments, which involved infection of HAE cells with A/California/04/2009 at 2 MOI. (f) Compares all significant host factors identified by transcriptomics in the SHAE002-R and SHAE003-R experiments, which involved infection of HAE cells with the SARS-CoV Urbani strain at 2 MOI. (g) Compares all significant host factors identified by proteomics in the ICL011-P and ICL012-P experiments, which involved infection of Calu-3 cells with A/Viet Nam/1203/2004 at 1 MOI.

Figure 3. Comparative analyses usage examples.

(a) Compares the significant host factors identified in the IM002-R experiment by transcriptomics at all time points by infecting C57BL/6 mice with 10⁶ PFU of H1N1 influenza strains A/Mexico/4482/2009, A/New Jersey/8/1976, or r1918. (b) Shows the comparison of significant factors identified by transcriptomics in the SCL005-R experiment that infected Calu-3 cells at 5 MOI with either wild-type SARS-CoV or a mutant containing a functional ORF6 knockout. (c) Results from the ICL004-R and ICL004-P experiments show the overlapping and unique host factors identified by transcriptomics and proteomics respectively for time points after (and including) 12 hpi in Calu-3 cells infected at 1 MOI with influenza strain A/Viet Nam/1203/2004.