. 2020 Jan 2;43(7):zsz321. doi: 10.1093/sleep/zsz321

Table 4.

Biochemical pathways associated with each biomarker model

Pathway	Pathway source	Compound hits	Total compounds in pathway	p-value	FDR
Logistic regression—compounds with and without 24-hour time-of-day patterns included (66)
Sphingolipid de novo biosynthesis	Reactome	4	29	<0.0001	0.0104
Sphingolipid metabolism	Reactome	4	52	<0.0001	0.0288
Immune System	Reactome	4	56	<0.0001	0.0288
Synthesis of PC	Reactome	3	22	<0.0001	0.0372
Synthesis of PS	Reactome	2	5	0.0001	0.0609
Acyl chain remodeling of PE	Reactome	2	5	0.0001	0.0609
Adaptive Immune System	Reactome	3	29	0.0001	0.0609
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	Reactome	2	6	0.0002	0.0661
Acyl chain remodeling of CL	Reactome	2	6	0.0002	0.0661
ABC transporters in lipid homeostasis^a	Reactome	2	7	0.0003	0.0767
Sphingolipid Metabolism	SMPDB	3	40	0.0004	0.0767
Gaucher Disease	SMPDB	3	40	0.0004	0.0767
Globoid Cell Leukodystrophy	SMPDB	3	40	0.0004	0.0767
Metachromatic Leukodystrophy (MLD)	SMPDB	3	40	0.0004	0.0767
Fabry disease	SMPDB	3	40	0.0004	0.0767
Krabbe disease	SMPDB	3	40	0.0004	0.0767
Golgi-to-ER retrograde transport ^a	Reactome	2	9	0.0005	0.0891
Glycerophospholipid biosynthesis	Reactome	3	46	0.0006	0.0913
HDL remodeling^a	Reactome	2	10	0.0006	0.0913
Plasma lipoprotein remodeling^a	Reactome	2	10	0.0006	0.0913
Synthesis of PG	Reactome	2	10	0.0006	0.0913
Metabolism of proteins	Reactome	4	117	0.0007	0.0949
Intra-Golgi and retrograde Golgi-to-ER traffic^a	Reactome	2	11	0.0007	0.0949
Phospholipid metabolism	Reactome	3	50	0.0007	0.0949
Linear SVM—Compounds with and without 24-hour time-of-day patterns included (47)
ABC transporters in lipid homeostasis^a	Reactome	2	7	<0.0001	0.0826
Golgi-to-ER retrograde transport^a	Reactome	2	9	0.0001	0.0826
HDL remodeling^a	Reactome	2	10	0.0002	0.0826
Plasma lipoprotein remodeling^a	Reactome	2	10	0.0002	0.0826
Synthesis of PG	Reactome	2	10	0.0002	0.0826
Intra-Golgi and retrograde Golgi-to-ER traffic^a	Reactome	2	11	0.0002	0.0826
Role of phospholipids in phagocytosis	Reactome	2	12	0.0003	0.0826
Surfactant metabolism	Reactome	2	13	0.0003	0.0826
ABC-family proteins mediated transport	Reactome	2	13	0.0003	0.0826
Plasma lipoprotein assembly_ remodeling_ and clearance	Reactome	2	13	0.0003	0.0826
Fcgamma receptor (FCGR) dependent phagocytosis	Reactome	2	14	0.0003	0.0903
Synthesis of PA	Reactome	2	15	0.0004	0.0936
PLC beta mediated events	Reactome	2	17	0.0005	0.0936
G-protein mediated events	Reactome	2	17	0.0005	0.0936
PI Metabolism	Reactome	2	17	0.0005	0.0936
Logistic regression and linear SVM—Compounds with 24-hour time-of-day patterns excluded (65)
Acyl chain remodeling of PC^b	Reactome	2	6	<0.0001	0.0671
Acyl chain remodeling of CL	Reactome	2	6	<0.0001	0.0671
ABC transporters in lipid homeostasis^a	Reactome	2	7	<0.0001	0.0671
COPI-independent Golgi-to-ER retrograde traffic^b	Reactome	2	7	<0.0001	0.0671
Phospho-PLA2 pathway^b	Reactome	2	7	<0.0001	0.0671
Golgi-to-ER retrograde transport^a	Reactome	2	9	0.0001	0.0673
HDL remodeling^a	Reactome	2	10	0.0002	0.0673
Plasma lipoprotein remodeling^a	Reactome	2	10	0.0002	0.0673
Choline metabolism in cancer—Homo sapiens (human)^b	KEGG	2	10	0.0002	0.0673
Ca-dependent events^b	Reactome	2	11	0.0002	0.0673
Intra-Golgi and retrograde Golgi-to-ER traffic^a	Reactome	2	11	0.0002	0.0673
ABC-family proteins mediated transport	Reactome	2	13	0.0003	0.0729
Plasma lipoprotein assembly_ remodeling_ and clearance	Reactome	2	13	0.0003	0.0729

Pathways within each biomarker model are ordered by p-value. Number of compounds indicates the number of compounds from the given biomarker model that appear in the pathway. Total compounds in the pathway indicates the number of compounds in the pathway that are in the background list. Numbers in parenthesis indicate total number of compounds in each biomarker model. FDR, false discovery rate.

^aPathways that overlap between all four biomarker models.

^bPathways that are unique to the models that exclude compounds with 24-hour time-of-day patterns.