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Influenza viruses are highly infectious RNA viruses that can cause acute respiratory illness. Influenza challenge studies can be used to test the efficacy of new vaccines however they require the accurate post-challenge classification of subjects by outcome which is limited in current methods that use artificial thresholds to assign "symptomatic" from "asymptomatic" phenotypes. 22 healthy adults (11 vaccinated) were inoculated with H3N2 influenza. Genome-wide gene expression data were generated from peripheral blood taken immediately before the challenge and at 12, 24 and 48 hours post-challenge. Variation in symptomatic scoring was found among those with laboratory confirmed influenza. By combining the dynamic transcriptomic data with the clinical parameters this variability can be reduced. We identified four subjects with severe laboratory confirmed flu that show differential gene expression in 1,103 probes 48 hours post-challenge compared to the remaining subjects. We have further reduced this profile to 6 genes that can be used to define these subjects.
| Project ID | Influenza |
|---|---|
| Status | Complete |
| Dates | 2010-2015 |
| Publication | PMID: 25345603 |
| Ethics |
| Sample information | |
|---|---|
| Organism | Homo sapiens |
| Organism part | Blood |
| Cell type | Whole blood |
| Experimental conditions | 11 subjects were vaccinated with MVA-NP+M1 thirty days before challenge. |
| Phenotype | See here for symptom score, seroconversion and viral shedding |
| Sample source | Whole blood collected in PAXgene tubes prior to influenza challenge (30 days after vaccination) and then at three further time points (12, 24 and 48 hours post-challenge) |
| Sequencing Project ID | Data type | Platform | Repository | Dataset ID | Status |
|---|---|---|---|---|---|
| P110160 | Gene Expression | Illumina HumanHT-12 v4 BeadChip | GEO | GSE61754 | Available |
See paper for full analysis. In brief, principal component analysis (PCA) and hierarchical clustering was performed to visualise variation in the dataset. This demonstrated that four subjects shared a similar profile of variance in gene expression. These four individuals were the only cases of LCI whose symptom score was moderate/severe rather than mild. Using the Limma package in R, 1,103 probes were differentially expressed between these four individuals and the remaining samples at 48 hours post-challenge. Using the same approach, no probes were differentially expressed at 12 or 24 hours post-challenge. The tool 'prediction analysis for microarrays' (pamr) was used to identify a six gene signature (CCL2, SEPT4, LAMP3, RTP4, MT1G and OAS3) which classified the samples into the two groups. This signature was validated using the Huang study (PMID 21901105).
The latest version of scripts used in the analysis of this project can be found here
| Name | |
|---|---|
| Name | [email protected] |