Table 2.

Top five metabolite associations with PHIV and periodontal disease measured by MRM-based quantitation and targeted extraction from DIA and DDA-based datasets, ranked by p-value for the F-test in the MRM dataset.

	PHIV/PHEU		moderate/without periodontitis		Interactionc		F-testd
	log2 ratioa	p-value	log2 ratiob	p-value	log2 ratio	p-value	p-value	FDRe
MRM
Cadaverine	0.04	0.92	1.07	0.005	−1.54	0.05	0.01	0.51
Methionine	0.20	0.35	0.32	0.10	−0.90	0.03	0.04	0.92
Histidine	0.22	0.41	−0.17	0.50	1.27	0.02	0.08	0.92
Arginine	−0.20	0.32	0.36	0.05	0.59	0.13	0.08	0.92
Cytosine	0.12	0.46	0.31	0.04	0.37	0.23	0.10	0.92
DIA
Cadaverine	−0.12	0.75	0.99	0.01	−0.69	0.35	0.06	0.89
Methionine	0.06	0.84	0.18	0.53	−1.44	0.01	0.09	0.89
Histidine	0.01	0.98	−0.25	0.33	1.33	0.01	0.06	0.89
Arginine	−0.26	0.33	0.15	0.55	0.43	0.38	0.56	0.92
Cytosine	0.06	0.78	−0.03	0.88	−0.58	0.14	0.52	0.92
DDA
Cadaverine	−0.04	0.85	0.43	0.06	0.00	0.99	0.29	0.89
Methionine	0.16	0.58	0.09	0.73	−1.16	0.04	0.20	0.89
Histidine	0.06	0.83	−0.15	0.53	1.17	0.03	0.13	0.89
Arginine	−0.18	0.58	0.58	0.06	0.97	0.13	0.11	0.89
Cytosine	0.41	0.22	0.26	0.40	0.67	0.30	0.35	0.89

^a: Using the notation HP, Hp, hP, and hp to represent average log₂ levels for the four subgroups as in Table 1, the log₂ ratio for PHIV/PHEU represents the contrast (HP-hP)/2+(Hp-hp)/2, so is positive when levels are on average higher in PHIV than in PHEU youth.

^b: The log₂ ratio for periodontitis +/− represents the contrast (HP-Hp)/2+(hP-hp)/2, so is positive when levels are on average higher in youth with periodontitis than in youth without periodontitis.

^c: The interaction term represents the contrast (HP-hP) – (Hp-hp) = (HP-Hp) – (hP-hp), so is positive when the log₂ ratio for PHIV/PHEU is greater in Perio+ than in Perio−, or when the log₂ ratio for Perio+/Perio− is greater in PHIV than in PHEU youth.) Note that under the null hypothesis of no difference between groups, the standard deviation of the interaction term is twice that of the main effects due to the 2s in the denominator of the main effects. Note also that coefficients for simple effects such as Hp-Hp can be recovered from the appropriate main effect (^a or ^b) +/− half the interaction term.

^d: An empirical Bayes-moderated F-statistic was used as an omnibus test for the two main effects and their interaction.

^e: False discovery rates (FDRs) were calculated using the Benjamini and Hochberg method (Benjamini, Hochberg 1995).