Table 1.
Cohort studies of pathobiology-driven patient phenotypic classification
| Endotypes | Cohort type (n) | Key biomarkers |
|---|---|---|
| Transcriptomic profiling | ||
| Subclass A–C [13] | Pediatric septic shock (98) | 44-gene classifier |
| SRS1 and SRS2 [14] | CAP (265) | 7-gene classifier: IDYRK2, DDNB1IP1, TDRD9, ZAP70, ARL14EP, MDC1 ADGRE3 |
| SRS1_FP and SRS2_FP [15] | Fecal peritonitis (117) | 6-gene classifier: CD163, CDHHC19, MME, FAM89A, ZBP1, B3GNT2 |
| Mars1–4 [16] | All-cause sepsis (306) | 2-gene ratios: Mars1: BPGM:TAP2, Mars2: GADD45A:PCGF5, Mars3: AHNAK:PDCD10, Mars4: IFIT5:GLTSCR2 |
| Inflammopathic, adaptive, coagulopathic [17] | Bacterial sepsis (700) | 33-gene classifier |
| Neutrophil pathways [18] | Sepsis with (29) and without ARDS (28) | OLFM4, LCN2 2, CD24, BPI |
| Metabolomics | ||
| Energy metabolism [27] | Septic shock (39), ICU controls (20) | ↑Glucose, 3-hydroxybutyrate, O-acetylcarnitine, succinate, creatine, creatine phosphate ↓Branched-chain amino acids and arginine |
| Lipid homeostasis and tryptophan catabolism [28] | Septic shock (20) | ↓Unsaturated long-chain PC and LPC, kynurenine |
| Defect in fatty acid-β-oxidation [29] | Community-acquired sepsis survivors (119) and nonsurvivors (31) | Acylcarnitine esters, amino/nucleic acid catabolites, glycolysis/citric acid cycle components |
| Lipid metabolism [30] | SIRS (29), Sepsis (30), sepsis-induced ARDS (31) | γ-glutamylphenylalanine, γ-glutamyltyrosine, 1-arachidonoyl-GPC (20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine |
| Lipid metabolism [31] | SIRS (42), CAP (67), IAI (60), UTI (73) BSI (26) | SM C22:3 and, lysoPCaC24:0, lysoPCaC26:1, putrescine, lysoPCaC18:0, SM C16:1 |
| Cellular function | ||
| Immunophenotype [34] | Sepsis (148) | Neutrophil, monocyte, and Treg phenotypes |
| Immunophenotype [35] | Sepsis (22) | Lymphocyte PD-1/PD-L1 expression |
| Immunophenotype [36] | Sepsis (505) | Monocyte and CD3, CD4, CD8 Tcell phenotypes |
| Endothelial permeability [37] | Sepsis (35) | Supernatants from whole blood treated with LPS |
| Endothelial permeability [38] | Primary (12) and secondary (6) sepsis | Neutrophils treated with fMLP |
CAP community-acquired pneumonia, PC phosphatidylcholines, LPC lysophosphatidylcholines, IAI intraabdominal infection, UTI urinary tract infection, BSI bloodstream infection, PD programmed death, LPS lipopolysaccharide, fMLP formyl, methionyl-leucyl-phenylalanine, SIRS systemic inflammatory response syndrome