Table 1.

Examples of genomic and modeling studies to classify septic human patients into various endotypes. Gene definitions can be found in Supplementary Table 1.

Endotype classification	Endotype outcome	Genes		Study population	Reference
		Upregulated	Downregulated
A, B, C				Prospective study; 98 children with septic shock were recruited; Males were prevalent in 2 of 3 endotypes	(33)
Subclass A group	Increased organ failure, highest mortality		44 key adaptive immune genes (i.e. T/B-cell related such as KAT2B, SOS1, JAK2, GK, TAF1, PTPRC, MA3K7 etc.) in subclass A compared to B and C.
			181 key zinc biology-related genes (i.e. ZnT/SLC, etc) downregulated in subclass A compared to B and C
Subclasses B and C groups	Decreased mortality
SRS 1, 2				Prospective study; Total of 371 adult patients with sepsis due to pneumonia were recruited; Males were prevalent in all cohorts	(11)
SRS1 group	Higher mortality and T-cell exhaustion	IRAK3, TOLLIP, CBL, PAG1, HIF1A, EPAS1, IL18RAP, CCR1, LDHA, GAPDH	LAT, CD247, HLA family, CIITA, RFX5, CCR3, MTOR, SIRT1, CD247
SRS2 group	Increased cell response to infection, low mortality	HLA family class II, T-cell and B-cell complexes
MARS 1–4				Prospective observational study; Total of 787 adult patients with sepsis due to pneumonia were recruited; Majority of patients recruited were Caucasian males	(34)
MARS 1 group	Highest 28-day mortality, decreased immune gene expression	BPGM, TAP2
MARS 2 group	Increased cytokine pathway expression	GADD45A, PCGF5
MARS 3 group	Increased adaptive immunity expression, lowest 28-day mortality	AHNAK nucleoprotein, PDCD10
MARS 4 group	Increased interferon gene expression	IFIT5,GLTSCR2/NOP53/NOL5A
Inflammopathic, adaptive and coagulopathic				Retrospective study; Total of 23 bacterial sepsis/inflammation datasets (12 in children, 11 in adults) were analyzed; Majority of patients in the cohorts were males from first-world nations	(35)
Inflammopathic group	Highest mortality and innate immunity expression	ARG1, LCN2, LTF, OLFM4	HLA-DMB
Adaptive group	Lowest mortality and increased adaptive immunity expression	YKT6, PDE4B, TWISTNB/POLR1F, BTN2A2	GADD45A, CD24, S100A12, STX1A
Coagulopathic group	High mortality and coagulopathy	KCNMB4, CRISP2, HTRA1, PPL	RHBDF2, ZCCHC4, YKT6, DDX6
Alpha, beta, gamma, delta					(5)
α group	Less organ dysfunction, normal blood tests and lowest mortality	IL10	d-dimer, IL6, IL8, TNFa, Procalcitonin, C-reactive protein
β group	Chronic illness and renal dysfunction	IGFBP7, COL4, TIMP2	IL10, IL66,procalcitonin, SELE, PAI1
γ group	Increased inflammation and fever	IL6, KIM1/HAVCR1,procalcitonin, PAI1, ICAM1, SELE
δ group	High coagulation and hypotension and the highest mortality	IL10, IL6, IL8, procalcitonin, TNFa, COL4, d -dimer, PAI1, VCAM1, TAT complex

MARS, Molecular Diagnosis and Risk Stratification of Sepsis; SRS, sepsis response signature.