Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers for CNS involvement in varicella zoster virus reactivation

Table 2 Diagnostic value of standard CSF parameters, metabolites, and their combinations

	Z. men_enc vs.					Z. facial vs.			Z. segmental vs.
	Control	Z. segmental	Z. facial	Ent. men	Bell’s	Z. segmental	Bell’s	Control	Bell’s	Control
(A) Standard CSF parameter
Leukocyte count	0.97***	0.94***	0.63	0.68	0.96***	0.70	0.72	0.80*	0.54	0.68
Protein concentration	0.81*	0.67	0.62	0.62	0.73	0.52	0.59	0.69	0.61	0.68
IgG index	0.74*	0.62	0.60	0.66	0.90**	0.51	0.77*	0.58	0.83**	0.63
Lactate	0.86**	0.82**	0.71	0.70	0.88**	0.67	0.75*	0.74*	0.65	0.65
(B) Metabolites
Best internally validated marker^a	SM C16:1	SM C16:1	PC ae C34.0	lysoPC a C26:1	Glycine	PC aa C32:0	SM(OH) C14:1	Tryptophan	Arginine	Serine
AUC	0.92***	0.90***	0.83**	0.87**	0.96***	0.76*	0.86**	0.84**	0.90***	0.77*
(C) Best classifier^b
No. of markers	2	3	1	2	2	2	3	4	1	3
Markers (frequency)	Glycine (1.0) PC aa C30:0 (0.9)	Leukocytes (1.0) SM C16:1 (1.0) total DMA (0.60)	PC ae C34:0 (1.0)	lysoPC a C26:1 (1.0) PC aa C32:0 (1.0)	Leukocytes (1.0) Glycine (1.0)	Leukocytes (0.73) PC aa C32:1 (1.0)	SM(OH) C14:1 (1.0) Glycine (0.96) Tryptophan (1.0)	Tryptophan (1.0) SM(OH) C14:1 (0.71) Leukocytes (1.0) Serine (0.84)	Arginine (1.0)	Serine (1.0) PC ae C36:3 (0.88) Methionine (0.67)
AUC	1.00	0.95	0.83	0.90	1.00	0.77	0.92	0.86	0.90	0.86
95% CI	0.87–1.0	0.76–1.0	N/A	0.57–1.0	0.89–1.0	0.51–0.91	0.61–0.98	0.55–0.98	N/A	0.53–0.96

Values correspond to areas under the receiver operator characteristic (ROC) curve (AUC) performed on continuous variables. Asymptotic significance (not corrected for multiple-hypothesis testing): *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. Italic values: lower CI > 0.5
Bell’s Bell’s palsy, CI confidence interval, DMA dimethylarginine, Ent. men enteroviral meningitis, N/A not applicable, PC phosphatidylcholine, SM sphingomyelin, SM (OH) hydroxysphingomyelin, Z. zoster, Z. men_enc Z. meningoencephalitis
^aAccording to the frequency of selection (0 = never selected; 1 = always selected) in the leave-one-out cross-validation. The marker with the higher AUC was selected if two markers had the same frequencies
^bBiomarker combination with the highest discriminatory ability identified by random forest construction as outlined in Methods. CIs of AUCs were evaluated based on 1000 bootstrap samples of the same size as the original data drawn with replacement

ISSN: 1742-2094