tetano
Editor, Senior Moderator
J Transl Med. 2017 Jun 8;15(1):134. doi: 10.1186/s12967-017-1235-3.
[h=1]Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.[/h] Muller J[SUP]1[/SUP], Parizotto E[SUP]1[/SUP], Antrobus R[SUP]1[/SUP], Francis J[SUP]2[/SUP], Bunce C[SUP]2[/SUP], Stranks A[SUP]1[/SUP], Nichols M[SUP]3[/SUP], McClain M[SUP]3[/SUP], Hill AVS[SUP]1[/SUP], Ramasamy A[SUP]1[/SUP], Gilbert SC[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis.
[h=4]METHODS:[/h] Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR.
[h=4]RESULTS:[/h] 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%).
[h=4]CONCLUSIONS:[/h] We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.
[h=4]KEYWORDS:[/h] Biomarker; Challenge trial; Influenza; Symptom scores; Transcriptomics
PMID: 28595644 PMCID: PMC5465537 DOI: 10.1186/s12967-017-1235-3
Free PMC Article
[h=1]Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.[/h] Muller J[SUP]1[/SUP], Parizotto E[SUP]1[/SUP], Antrobus R[SUP]1[/SUP], Francis J[SUP]2[/SUP], Bunce C[SUP]2[/SUP], Stranks A[SUP]1[/SUP], Nichols M[SUP]3[/SUP], McClain M[SUP]3[/SUP], Hill AVS[SUP]1[/SUP], Ramasamy A[SUP]1[/SUP], Gilbert SC[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis.
[h=4]METHODS:[/h] Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR.
[h=4]RESULTS:[/h] 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%).
[h=4]CONCLUSIONS:[/h] We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.
[h=4]KEYWORDS:[/h] Biomarker; Challenge trial; Influenza; Symptom scores; Transcriptomics
PMID: 28595644 PMCID: PMC5465537 DOI: 10.1186/s12967-017-1235-3
Free PMC Article