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The tier one criterion is relatively loose and was based on nominal P-values, i.e., pathways with nominal P < 0.01 were selected.
To generate an objective comparison, we defined a relatively loose criterion based on nominal P-values, i.e., the tier one criterion (nominal P-value < 0.01), and a more strict criterion based on adjusted P-values after multiple testing correction, i.e., the tier two criterion (FDR < 0.2).
Finally, conclusions are based on nominal p-values at 5% statistical significance and therefore require replication in independent studies.
In addition, statistical significance was independently assessed by using an approach based on the False Discovery Rate -FDR- [ 44], that was calculated based on nominal P-values every 30 cM, as well as by employing a parametric bootstrap method [ 45].
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For poly I C/Lyovec 6 h, genes were selected based on nominal P value < 0.05 and FC ≥ 1.3 or ≤ −1.3 due to FDR 5% resulting in zero genes.
First, a false discovery rate (FDR) was calculated based on the nominal P-values every 30 cM, with a result of 0.018 for a P-value lower than 0.001.
Among BENEFIT participants, the expression of 63 genes was found to be regulated by 25(OH D based on a nominal P-value threshold of 0.05 (Table S4).
FDR and nominal P were similar at 4 days, the analysis was based on the nominal P values (all FDR values < 10% when nominal P < 0.05).
Differentially expressed genes (selected based on a nominal P value ≤ 0.05 and FC ≥ ± 1.3) that were associated with a canonical pathway in Ingenuity's Knowledge Base were used for pathway analysis.
We made the conclusion based on the nominal P value from single marker analysis and cannot exclude the possibility that our decision would have been different if a much larger study populations would have been available.
Patients in the topiramate group exhibited significant reductions in reexperiencing symptoms (CAPS cluster B: topiramate = 74.9%; placebo = 50.2%; p =.038) and reductions approaching statistical significance, based on a nominal p value, were noted in mean total Clinical Global Impressions-Improvement Scale scores (topiramate = 1.9 ± 1.2; placebo = 2.6 ± 1.1; p =.055).
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