Transcriptome changes in stages of non-alcoholic fatty liver disease

Table 1 Top canonical pathways for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis identified by Ingenuity Pathway Analysis

	Overlap	P value
Top canonical pathways in NAFLD vs healthy control
Liver X receptor / retinoid X receptor activation	5/121	4.35E-05
Superpathway of cholesterol biosynthesis	3/29	1.08E-04
Granulocyte adhesion and diapedesis	5/173	2.34E-04
CREB signaling	8/596	6.25E-04
Mevalonate pathway I	2/14	8.96E-04
Top canonical pathways in NASH vs healthy control
Cholesterol biosynthesis I	4/13	5.48E-05
Cholesterol Biosynthesis II (via 24,25-dihydrolanosterol)	4/13	5.48E-05
Cholesterol biosynthesis III (via desmosterol)	4/13	5.48E-05
IGF-1 signaling	9/106	9.16E-05
Superpathway of cholesterol biosynthesis	5/28	1.05E-04

NAFLD: Non-alcoholic fatty liver disease; CREB: cAMP response element binding protein.

Table 2 Summary of the list genes that are the most upregulated and downregulated in our meta-analysis of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis liver samples compared to healthy controls

Top upregulated genes				Top downregulated genes
NAFLD vs Healthy		NASH vs Healthy		NAFLD vs Healthy		NASH vs Healthy
XIST	0.326	Crystallin alpha A	1.185	LINC02535	-0.198	MT1L	-0.454
PEG10	0.267	CYP7A1	0.409	GPR88	-0.194	CYR61	-0.386
SUCO	0.252	BBOX1	0.381	CYP1A1	-0.170	FOSB	-0.339
CBWD5	0.239	TAF4B	0.355	IGFBP2	-0.168	IGFBP2	-0.326
TMEM154	0.228	FNDC5	0.346	P4HA1	-0.166	FOS	-0.275
HMGCR	0.225	MROH2A	0.293	TSPAN13	-0.159	CAPZA3	-0.254
LINC00885	0.216	Fc alpha and mu receptor	0.265	NR4A2	-0.148	CSRNP1	-0.254
Chitinase 3 Like 1	0.186	IL13RA2	0.252	PER3	-0.145	PCDHB19P	-0.252
MEP1B	0.181	ABHD1	0.250	SHBG	-0.135	Nicotinamide phosphoribosyltransferase	-0.240
Phosphodiesterase 11A	0.180	Muscular LMNA interacting protein	0.229	CENPO	-0.131	RASD1	-0.237

NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis, PEG10: Paternally expressed imprinted gene 10; SHBG: Sex hormone-binding globulin.

Table 3 Top disease functions for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis identified by Ingenuity Pathway Analysis

Top disease functions in NAFLD vs healthy control	P values
Inflammatory response	1.67E-03
Liver lesion	6.59E-05
Cell movement of epithelial cells	3.88E-04
Activation of cells	5.30E-04
Synthesis of lipid	5.49E-08
Accumulation of lipid	6.12E-04
Concentration of lipid	2.38E-06
Fibrosis	3.75E-05
Secretion of lipid	1.06E-03
Hepatic injury	1.54E-04
Organismal injury and abnormalities	5.10E-16
Cancer	3.47E-15
Dermatologic diseases and conditions	5.20E-11
Metabolic disease	6.69E-10
Lipid metabolism	8.09E-12
Molecular transport	7.06E-12
Small molecule biochemistry	9.86E-11
Cell death and survival	5.05E-8
Cellular movement	6.28E-8
Adipogenesis	1.31E-7

NAFLD: Non-alcoholic fatty liver disease.

Table 4 Top five molecular networks associated with genetic differences in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis liver biopsies compared to healthy controls. Disease networks were identified using Ingenuity Pathway Analysis

Top molecular networks in NAFLD vs healthy control
Lipid metabolism, small molecule biochemistry, vitamin and mineral metabolism	34
Cell-to-cell signaling and interaction, cellular movement, hematological system development and function	23
Connective tissue disorders, inflammatory disease, organismal injury and abnormalities	19
Cellular development, connective tissue development and function, skeletal and muscular system development and function	16
Cell death and survival, neurological disease, organismal injury and abnormalities	16
Amino acid metabolism, molecular transport, small molecule biochemistry	34
Cellular development, skeletal and muscular system development and function, tissue development	34
Hereditary disorder, neurological disease, organismal injury and abnormalities	32
Digestive system development and function, lipid metabolism, small molecule biochemistry	29
Cell cycle, cell death and survival, cellular movement	29

NAFLD: Non-alcoholic fatty liver disease.