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Copyright ©The Author(s) 2018.
World J Gastroenterol. Apr 21, 2018; 24(15): 1601-1615
Published online Apr 21, 2018. doi: 10.3748/wjg.v24.i15.1601
Table 1 List of pathways involved in nonalcoholic fatty liver disease selected from significant Q-values that dependent on both genes and metabolites analyzed jointly
Pathway nameQ-joint
Solute carriers -mediated transmembrane transport1.23E-12
Transmembrane transport of small molecules9.66E-12
Transport of glucose and other sugars bile salts and organic acids metal ions and amine compounds8.40E-10
Leukotriene biosynthesis8.71E-10
Transport of glucose and other sugars bile salts and organic acids metal ions and amine compounds1.91E-09
Transport of inorganic cations-anions and amino acids-oligopeptides4.27E-09
Amino acid and oligopeptide SLC transporters1.10E-08
Transport of inorganic cations/anions and amino acids/oligopeptides2.40E-08
tRNA Aminoacylation3.03E-08
Gamma-glutamyl cycle3.61E-08
tRNA charging5.96E-08
mRNA protein and metabolite induction pathway by cyclosporine A8.47E-08
Class I MHC mediated antigen processing & presentation1.73E-07
Na+/Cl- dependent neurotransmitter transporters3.10E-07
Amino acid transport across the plasma membrane3.72E-07
S-methyl-5-thio-alpha;-D-ribose 1-phosphate degradation6.17E-07
Amine compound solute carrier transporters6.17E-07
Protein digestion and absorption - homo sapiens (human)2.13E-06
Amino acid interconversion2.21E-06
Biochemical pathways part I2.34E-06
Amino acid metabolism3.96E-06
Aminoacyl-tRNA biosynthesis - homo sapiens (human)6.88E-06
Metabolism of amino acids and derivatives8.72E-06
Mineral absorption - homo sapiens (human)1.47E-05
Cytosolic tRNA aminoacylation2.86E-05
Mitochondrial tRNA aminoacylation2.86E-05
tRNA Aminoacylation2.86E-05
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism0.000159
Gene expression0.000181
Tryptophan catabolism0.000275
Phase II conjugation0.000426
Phenylalanine and tyrosine catabolism0.003
Glutamine and glutamate metabolism - homo sapiens (human)0.00376
Glutaminolysis and cancer0.00493
Glycine metabolism0.0052
Glutamate glutamine metabolism0.00665
Recycling of bile acids and salts0.00669
Glycine serine alanine and threonine metabolism0.0101
Branched-chain amino acid catabolism0.0103
OMICs-integrative analysis was performed using the IMPaLA (integrated molecular pathway level analysis, http://impala.molgen.mpg.de)[67] platform. A joined adjusted P-value (Q-value) was calculated to control for multiple testing by false discovery rate.
Table 2 List of pathways involved in nonalcoholic fatty liver disease selected from significant Q-values independently on whether they represent the effect of gene/s or metabolite/s only
Pathway namePathway sourceQ-joint
AdipogenesisWikipathways2.00E-17
Non-alcoholic fatty liver disease (NAFLD) - homo sapiens (human)KEGG2.33E-17
MetabolismReactome3.72E-17
AGE-RAGE pathwayWikipathways4.22E-17
Vitamin B12 MetabolismWikipathways5.24E-17
Hepatitis B - homo sapiens (human)KEGG1.79E-16
Folate metabolismWikipathways1.29E-15
Selenium micronutrient networkWikipathways3.87E-15
TNF signaling pathway - homo sapiens (human)KEGG5.77E-15
JAK-STAT-coreSignalink1.99E-14
Adipocytokine signaling pathway - homo sapiens (human)KEGG7.07E-14
Nuclear receptors meta-pathwayWikipathways1.26E-13
IL1 and megakaryocytes in obesityWikipathways2.73E-13
AGE-RAGE signaling pathway in diabetic complications - homo sapiens (human)KEGG3.79E-13
Spinal cord injuryWikipathways5.44E-13
Malaria - homo sapiens (human)KEGG7.09E-13
Metabolism of lipids and lipoproteinsReactome7.09E-13
SLC-mediated transmembrane transportReactome1.23E-12
Pathways in cancer - homo sapiens (human)KEGG1.41E-12
Inflammatory bowel disease (IBD) - homo sapiens (human)KEGG2.25E-12
Lung fibrosisWikipathways2.63E-12
Integrated pancreatic cancer pathwayWikipathways3.10E-12
PI3K-Akt signaling pathway - homo sapiens (human)KEGG3.28E-12
Chagas disease (American trypanosomiasis) - homo sapiens (human)KEGG4.67E-12
HIF-1 signaling pathway - homo sapiens (human)KEGG4.67E-12
AMPK signaling pathway - homo sapiens (human)KEGG9.56E-12
Transmembrane transport of small moleculesReactome9.66E-12
Central carbon metabolism in cancer - homo sapiens (human)KEGG1.41E-11
Jak-STAT signaling pathway - homo sapiens (human)KEGG5.75E-11
DNA damage response (only ATM dependent)Wikipathways7.27E-11
Cytokine-cytokine receptor interaction - homo sapiens (human)KEGG1.01E-10
Longevity regulating pathway - homo sapiens (human)KEGG1.02E-10
Toll-like receptor signaling pathwayWikipathways2.12E-10
Toll-like receptor signaling pathway - homo sapiens (human)KEGG3.94E-10
Toxoplasmosis - homo sapiens (human)KEGG4.73E-10
ABC transporters - homo sapiens (human)KEGG5.94E-10
Transport of glucose and other sugars bile salts and organic acids metal ions and amine compoundsWikipathways8.40E-10
Leukotriene biosynthesisHumanCyc8.71E-10
Insulin resistance - homo sapiens (human)KEGG1.14E-09
Transport of glucose and other sugars bile salts and organic acids metal ions and amine compoundsReactome1.91E-09
Sudden infant death syndrome (SIDS) susceptibility pathwaysWikipathways2.12E-09
Cytokines and inflammatory responseWikipathways2.17E-09
AP-1 transcription factor networkPID2.22E-09
FoxO signaling pathway - homo sapiens (human)KEGG3.05E-09
Leptin signaling pathwayWikipathways3.57E-09
Transport of inorganic cations-anions and amino acids-oligopeptidesWikipathways4.27E-09
Oncostatin M signaling pathwayWikipathways5.72E-09
Focal adhesion-PI3K-Akt-mTOR-signaling pathwayWikipathways6.53E-09
Amino acid and oligopeptide SLC transportersReactome1.10E-08
ApoptosisWikipathways1.41E-08
Apoptotic signaling pathwayWikipathways1.41E-08
Photodynamic therapy-induced NF-kB survival signalingWikipathways1.84E-08
JAK STAT molecularvariation 1INOH2.04E-08
MAPK signaling pathwayWikipathways2.04E-08
Aryl hydrocarbon receptorWikipathways2.35E-08
Transport of inorganic cations/anions and amino acids/oligopeptidesReactome2.40E-08
tRNA aminoacylationWikipathways3.03E-08
gamma-glutamyl cycleHumanCyc3.61E-08
Glucose homeostasisWikipathways4.08E-08
Validated transcriptional targets of AP1 family members Fra1 and Fra2PID4.13E-08
Hepatitis C and hepatocellular carcinomaWikipathways4.26E-08
Calcineurin-regulated NFAT-dependent transcription in lymphocytesPID4.29E-08
Prostate cancer - homo sapiens (human)KEGG4.29E-08
Tuberculosis - homo sapiens (human)KEGG4.45E-08
Apoptosis - homo sapiens (human)KEGG4.54E-08
tRNA chargingHumanCyc5.96E-08
Transcription factor regulation in adipogenesisWikipathways6.27E-08
Sterol regulatory element-binding proteins (SREBP) signallingWikipathways6.27E-08
Integrated lung cancer pathwayWikipathways6.43E-08
TNF related weak inducer of apoptosis (TWEAK) signaling pathwayWikipathways8.14E-08
mRNA protein and metabolite inducation pathway by cyclosporin AWikipathways8.47E-08
PPAR signaling pathwayWikipathways9.54E-08
Immune systemReactome9.57E-08
Regulation of lipid metabolism by peroxisome proliferator-activated receptor alpha (PPARalpha)Wikipathways1.13E-07
AMP-activated protein kinase (AMPK) signalingWikipathways1.34E-07
Photodynamic therapy-induced NFE2L2 (NRF2) survival signalingWikipathways1.52E-07
Leptin insulin overlapWikipathways1.65E-07
Class I MHC mediated antigen processing and presentationWikipathways1.73E-07
Caspase cascade in apoptosisPID1.99E-07
Overview of nanoparticle effectsWikipathways2.17E-07
Alpha6Beta4IntegrinNetPath2.29E-07
VEGFA-VEGFR2 signaling pathwayWikipathways2.30E-07
HIV-1 Nef: Negative effector of Fas and TNF-alphaPID2.65E-07
Innate immune systemReactome2.69E-07
Na+/Cl- dependent neurotransmitter transportersReactome3.10E-07
Colorectal cancer - homo sapiens (human)KEGG3.42E-07
Regulation of toll-like receptor signaling pathwayWikipathways3.64E-07
stress induction of hsp regulationBioCarta3.64E-07
Amino acid transport across the plasma membraneReactome3.72E-07
Programmed cell deathReactome3.85E-07
Apoptosis modulation and signalingWikipathways4.42E-07
SREBF and miR33 in cholesterol and lipid homeostasisWikipathways4.84E-07
JAK STAT pathway and regulationINOH5.42E-07
OMICs-integrative analysis was performed using the IMPaLA (Integrated Molecular Pathway Level Analysis, http://impala.molgen.mpg.de)[67] platform. A joined adjusted P-value (Q-value) was calculated to control for multiple testing by false discovery rate.