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- Processed GEO [GSE152075](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE152075) (n = 484 nasopharyngeal swabs) to a balanced subset (n = 60) for the primary differential expression analysis
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- Identified **1,773 thresholded DE genes** in the balanced subset (FDR < 0.05, |log₂FC| > 1), dominated by canonical interferon-stimulated genes
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- Full-cohort sensitivity analysis identified **4,378 thresholded DE genes**, with **1,266** shared with the balanced analysis and **99.8%** effect-direction concordance
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- Enriched pathways: GO "response to virus", KEGG "Coronavirus disease - COVID-19" (FDR = 4.5e-39)
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- Enriched pathways: GO "response to virus", KEGG "Coronavirus disease - COVID-19" (FDR = 2.9e-39)
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-**Extended: Viral load stratification** — COVID-positive samples stratified by N1 Ct value into high/low viral load groups with independent DE analysis and continuous ISG–Ct correlation, extending the original continuous regression approach with a group-comparison framework
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-**Extended: Sex-stratified interaction analysis** — Condition-by-sex interaction model (`~ condition * gender`) to identify genes with sex-differential transcriptional responses, complementing the original study's sex-adjusted analysis with a formal interaction test
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- Extracts full GEO covariates (viral load Ct, age, sex, sequencing batch) for covariate-aware analyses
@@ -37,7 +37,7 @@ GSE152075 (n=484, GEO)
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│
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├──→ 04 Sensitivity ─── Full cohort (n=484) DE → concordance check (99.8% sign agreement)
Results are dominated by interferon-stimulated genes (ISGs) characteristic of antiviral immunity. Ranking and volcano visualization use shrunken log2 fold changes to stabilize effect-size estimates for lower-count genes while preserving the raw significance calls.
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@@ -122,15 +122,15 @@ Hierarchical clustering of top 50 DE genes shows consistent expression patterns
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### Pathway Enrichment
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**529 GO Biological Process terms** and **26 KEGG pathways** significantly enriched (FDR < 0.05).
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**397 GO Biological Process terms** and **23 KEGG pathways** significantly enriched (FDR < 0.05).
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Top GO terms: cytoplasmic translation, response to virus, defense response to virus.
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