Table 2.
Enriched Gene Sets Based on Cell Type and Clinical Outcome
| VFD ≥ 18 (Good Outcome) | VFD ≤ 7 (Poor Outcome) | ||||||
|---|---|---|---|---|---|---|---|
| Gene Set | FDR | Gene | FC | Gene Set | FDR | Gene | FC |
| Alveolar macrophages | |||||||
| TNFα signaling via NF-κB | <0.01 | CCR7 | 3.1 | MYC targets V1 | <0.01 | CAV1 | 2.5 |
| IFN-γ response | <0.01 | FOSB | 2.6 | Peroxisome | <0.01 | FHL2 | 1.8 |
| Inflammatory response | <0.01 | DUSP2 | 2.5 | UV response down | <0.01 | TFPI | 1.6 |
| IFN-α response | <0.01 | IL6 | 2.3 | Protein secretion | 0.02 | SLC25A4 | 1.6 |
| Allograft rejection | <0.01 | STAT4 | 2.3 | Pancreas β cells | 0.03 | LAMC1 | 1.6 |
| Hypoxia | <0.01 | NR4A2 | 2.1 | ERBB2 | 1.6 | ||
| Complement | <0.01 | IL23A | 2.1 | EFEMP1 | 1.5 | ||
| IL2 STAT5 signaling | 0.01 | SLAMF1 | 2.1 | SCGB1A1 | 1.4 | ||
| IL6 JAK STAT3 signaling | 0.02 | CXCL2 | 2.0 | FBLN5 | 1.4 | ||
| UV response up | 0.03 | DLL1 | 2.0 | TSPAN8 | 1.4 | ||
| Coagulation | 0.03 | DNAJB1 | 2.0 | SLC7A1 | 1.4 | ||
| Apoptosis | 0.04 | MMP9 | 1.9 | FOXA2 | 1.4 | ||
| Notch signaling | 0.04 | TNFAIP3 | 1.9 | GJA1 | 1.3 | ||
| MMP12 | 1.9 | IDH1 | 1.3 | ||||
| C8B | 1.8 | ERH | 1.3 | ||||
| GCH1 | 1.8 | ATP2B4 | 1.2 | ||||
| HAS1 | 1.8 | ICA1 | 1.2 | ||||
| IRAK2 | 1.7 | NFIB | 1.2 | ||||
| CD274 | 1.7 | GNPAT | 1.2 | ||||
| ICOS | 1.7 | CAV2 | 1.2 | ||||
| IL1B | 1.7 | YWHAQ | 1.2 | ||||
| PROK2 | 1.6 | IARS | 1.2 | ||||
| ZC3H12A | 1.6 | MAFB | 1.2 | ||||
| HLA-DQA1 | 1.6 | RPS2 | 1.2 | ||||
| CTSZ | 1.6 | SMARCC1 | 1.2 | ||||
| IL18BP | 1.5 | ACP1 | 1.2 | ||||
| IL1A | 1.5 | PTPRM | 1.2 | ||||
| CXCL9 | 1.5 | APEX1 | 1.2 | ||||
| CXCR7 | 1.5 | CNBP | 1.1 | ||||
| EIF5A | 1.4 | C1QBP | 1.1 | ||||
| Peripheral blood monocytes | |||||||
| IFN-α response | <0.01 | HLA-DQA1 | 1.9 | MYC targets V1 | <0.01 | EGR2 | 2.1 |
| IFN-γ response | <0.01 | XAF1 | 1.3 | Oxidative phosphorylation | <0.01 | FOSB | 1.8 |
| Unfolded protein response | 0.01 | WFS1 | 1.3 | MTORC1 signaling | 0.01 | IL1R2 | 1.6 |
| ISG15 | 1.3 | Adipogenesis | 0.01 | EGR1 | 1.6 | ||
| HLA-DMA | 1.3 | Fatty acid metabolism | 0.01 | CA2 | 1.5 | ||
| DNAJA4 | 1.2 | IL2 STAT5 signaling | 0.03 | CXCL10 | 1.4 | ||
| DHX58 | 1.2 | Peroxisome | 0.03 | AKR1C3 | 1.4 | ||
| SDAD1 | 1.2 | Xenobiotic metabolism | 0.04 | PTGS2 | 1.4 | ||
| PIM1 | 1.2 | TNFα signaling via NF-κB | 0.05 | SH3BGRL2 | 1.3 | ||
| TRIM25 | 1.2 | E2F targets | 0.05 | TUBA4A | 1.3 | ||
| SLC25A28 | 1.2 | TPST1 | 1.3 | ||||
| SAMD9L | 1.2 | ATP1B3 | 1.3 | ||||
| CD86 | 1.2 | FH | 1.3 | ||||
| CD74 | 1.2 | ACTR3 | 1.3 | ||||
| DCP2 | 1.2 | PTGES3 | 1.3 | ||||
| SPCS3 | 1.2 | ME1 | 1.3 | ||||
| SP110 | 1.2 | ID2 | 1.3 | ||||
| PARP12 | 1.2 | CNBP | 1.3 | ||||
| PELI1 | 1.2 | PROS1 | 1.3 | ||||
| SELL | 1.1 | HMGB2 | 1.2 | ||||
| DNAJB9 | 1.1 | GPR65 | 1.2 | ||||
| TNFAIP3 | 1.1 | GSTZ1 | 1.2 | ||||
| ADAR | 1.1 | HSD17B11 | 1.2 | ||||
| CIITA | 1.1 | PPP1R15A | 1.2 | ||||
| MOV10 | 1.1 | SDPR | 1.2 | ||||
| EDC4 | 1.1 | ACOX2 | 1.2 | ||||
| PDE4B | 1.1 | CES1 | 1.2 | ||||
| ARFGAP1 | 1.1 | PSMD14 | 1.2 | ||||
| ATF3 | 1.1 | ALDH2 | 1.2 | ||||
| RBCK1 | 1.1 | ARG2 | 1.2 | ||||
Definition of abbreviations: FC = fold change; FDR = false discovery rate; UV = ultraviolet; VFD = ventilator-free days.
Gene sets are enriched hallmark gene sets curated from the Molecular Signature Database (http://software.broadinstitute.org/gsea/msigdb). Displayed are the significantly enriched gene sets (FDR < 0.05) for each cell type and outcome and a list of the 30 most upregulated genes (fold change) compiled from all the leading-edge genes (9) driving each of the enriched gene sets. These gene lists represent the predominant biological themes that drove each of the gene set associations listed; however, no individual gene met the threshold for statistical significance after multiple hypothesis testing.