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Table 1 Cohort studies of pathobiology-driven patient phenotypic classification

From: Heterogeneity in sepsis: new biological evidence with clinical applications

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
  1. 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