Table 3.

Model performance statistics for endotype predictions and outcome measures predicting impending severity. The AUC ( Accuracy), sensitivity, and specificity of the models, expressed as percent is provided. The performance of the 40 gene signature and the top 5/148 performing gene pairs is shown. For the severity comparisons, comparisons are based on patient groups with SOFA scores measured 24 H post ER/ICU admission: High (≥ 5), Intermediate (≥ 2 and < 5), and Low (< 2). The cellular reprogramming/endotoxin tolerance (CR) Signature is as per Pena et al.²³ The severity and mortality signatures were further reduced by filtering the genes input to LASSO using a more stringent fold change cut off (top 25% highest fold changes).

		Cross Validation (%)
Comparison	Gene Sets	AUC Accuracy	Sensitivity	Specificity
Severitya
High vs. Low Severity	Severity Signature	80	72	73
	Reduced Severity Signaturec	80	76	70
	CR Signature	75	70	68
	Reduced CR Signatured	77	73	73
High + Intermediate vs. Low Severity	Severity Signature	71	72	60
	Reduced Severity Signaturec	69	64	63
	CR Signature	68	64	62
	Reduced CR Signatured	73	67	67
Survived vs Died	Mortality	75	68	70
	Reduced Mortality Signaturee	67	62	62
	CR Signature	60	57	61
	Reduced CR Signaturec	62	60	61
Endotypesb
Multinomial Model	40 gene set	96	81	95
NPS vs. all others	MLLT1/NSUN7	97	93	91
INF vs. all others	SPTA1/GLRX5	95	90	85
IHD vs. all others	MAP7/PLCB1	90	85	79
IFN vs. all others	PLEKHO1/EPSTI1	86	83	76
ADA vs. all others	CENPF/PDIA4	97	87	91

^aAUCs obtained in the full (ER + ICU) discovery cohorts.

^bAUCs of data-driven endotype gene sets obtained in ER discovery cohort.

^cReduced Severity Signature = TNIP3, DSP, RHAG, G0S2, ITGB4, GPR84, FAM83A, PCOLCE2, CXCL8, SDC2, PRTN3, ELANE

^dReduced CR signature = CD300LF, CPVL, CST3, HK3, MGST1, RAB13, RETN, S100A12

^eReduced Mortality Signature = HGF, DHRS9, SIGLEC1, MS4A4A, OAS2, MMP8, RGL1, SLC51A, OSBP2, IFIT1