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Table 5 Related pathways across transcriptomics, proteomics and metabolomics

From: Systematic analysis of multi-omics data reveals component-specific blood-based biomarkers for Parkinson’s disease

S No.

Blood Component

Top 10 pathways affected

Level in PD (compared to healthy controls)

Transcriptomics

1

Whole blood

Nil

Downregulated

Dilated cardiomyopathy, Hypertrophic cardiomyopathy, Cardiac muscle contraction, ECM-receptor interation, Platelet activation, Arrhythmogenic righ ventricular cardiomyopathy, Antigen processing and presentation, Adrenergic signaling in cardiomyocytes, Focal adhesion,

Upregulated

2

Whole blood

Nil

Downregulated

Staphylococcus aureus infection, Complement and coagulation cascades

Upregulated

3

Whole blood

Nil

Downregulated

Osteoclast differentiation, Leishmaniasis, Tuberculosis,

Upregulated

4

Whole blood

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Downregulated

5

Whole blood

Nil

Downregulated

Osteoclast differenciation, Natural killer cell mediated cytotoxicity, Antigent processing and presentation, B cell receptor signalling pathway, Graft-versus-host disease, Lysosome, Phagosome, Chemokine signaling pathway, Fc gamma R-mediated phagocytosis, Tuberculosis

Upregulated

6

Whole blood

Parkinson Disease, Perussis, Prion Disease, Huntington disease,

Downregulated

Nil

Upregulated

7

peripheral blood mononuclear cells (PBMCs)

Th1 and Th2 cell differentiation, Th17 cell differentiation, Epstein-Barr virus infection, Toxoplasmosis, Leukocyte transendothelial migration, Human immunodeficiency virus 1 infection, Tuberculosis, Leishmaniasis, Pathways in cancer, Human cytomegalovirus infection

Downregulated

Porphyrin and chlorophyll metabolism, Amoebiasis

Upregulated

8

peripheral blood mononuclear cells (PBMCs)

Sulfur metabolism, Collecting duct acid secretion, Glycine, serine and threonine metabolism, Porphyrin and chlorophyll metabolism, Malaria

Downregulated

9

Whole blood

Nil

Downregulated

Endocrine and other factor-regulated calcium reabsorption, Nitrogen metabolism,

Upregulated

10

Whole blood / leukocytes

Citrate cycle (TCA cycle), Pyruvate metabolism, Cocaine addiction, Aminoacyl-tRNA biosynthesis, Amphetamine addiction, Salmonella infection, Parkinson disease, Prion disease, Huntington Disease, Amyotrophic lateral sclerosis

Downregulated

Nil

Upregulated

11

peripheral blood mononuclear cell (PBMC)

Autophagy, Mitophagy, RIG-I-like receptor signaling pathway, NOD-like recptor signaling pathway, Shigellosis

Downregulated

Lysosome, Glycosaminoglycan degradation, Other glycan degradation, Glycosphingolipid biosynthesis, Phagosome, Sphinagolipid metabolism, Collecting duct acid secretion, Apoptosis, Tuberculosis, Synaptic vesicle cycle

Upregulated

12

Whole blood

Nil

Downregulated

Nil

Upregulated

13

peripheral blood mononuclear cells (PBMCs)

Nil

Downregulated

Inflammatory bowel disease, Cytokine-cytokin receptor interaction, African trypanosomiasis, Malaria, Perussis, Leishmaniasis, Asthma, IL-17 signaling pathway, Hematopoietic cell lineage, Amoebiasis

Upregulated

14

Whole blood

Nil

Downregulated

15

Whole blood

Ubiquitin mediated proteolysis, Protein processing in endoplasmis reticulum, Parkinson disease

Downregulated

Fructose and mannose metabolism, Inflammatory bwel disease

Upregulated

16

Whole blood

Nil

Downregulated

Arachidonic acid metabolism

Upregulated

17

Peripheral blood

Nil

Downregulated

18

Blood Serum

Nil

Upregulated

Blood Serum

Viral protein interaction with cytokine and cytokine receptor,

Upregulated

Proteomics

1

Plasma EV

Parkinson disease, MAPK signaling pathway, Alzheimer disease, Pathways of neurodegeneration

Upregulated

2

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

3

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

4

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

5

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

6

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

7

Plasma EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration,

Upregulated

8

Plasma EV

Ferroptosis, Prion disease, Pathways of neurodegeneration,

Upregulated

9

Plasma EV

Nil

Upregulated

10

Plasma EV

Complement and coagulation cascades, Staphylococcus aureus infection, Coronavirus disease, Vitamin digestion and absorption, African trypanosomiasis, Fat digestion and absorption, Cholesterol metabolism, PPAR signaling pathway, Pertussis, Platelet activation,

Downregulated

11

Plasma EV

Proteasome, Gastric acid secretion, Endocytosis, Parkinson disease, Phagosome, Aldosterone-regulated sodium reabsorption, Salivary secretion, Adrenergic signaling in cardiomyocytes, Aldosterone synthesis and secretion, Glycolysis / Gluconeogenesis, Endocrine and other factor-regulated calcium reabsorption,

Upregulated

Proteasome, Pentose phosphate pathway, Spinocerebellar ataxia, Prion disease, Parkinson disease, Amyotrophic lateral sclerosis, Huntington disease, Pathways of neurodegeneration, Glycolysis / Gluconeogenesis, Cysteine and methionine metabolism,

Downregulated

12

Serum EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

Nil

Downregulated

13

Serum EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Downregulated

14

Serum EV

Asthma, African trypanosomiasis, Allograft rejection, Graft-versus-host disease, Type I diabetes mellitus, Type II diabetes mellitus, Malaria, Legionellosis, Inflammatory bowel disease, Fc epsilon RI signaling pathway,

Upregulated

Thermogenesis, Citrate cycle (TCA cycle), Asthma, Oxidative phosphorylation, Non-alcoholic fatty liver disease, Diabetic cardiomyopathy, Parkinson disease, Melanoma, Prion disease, Huntington disease,

Downregulated

15

Serum EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

16

Serum EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

17

Serum EV

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

18

Serum EV

Complement and coagulation cascades, Platelet activation, Pertussis, Systemic lupus erythematosus, Neutrophil extracellular trap formation, ECM-receptor interaction, Hypertrophic cardiomyopathy, Coronavirus disease, Staphylococcus aureus infection, Dilated cardiomyopathy,

Upregulated

Complement and coagulation cascades, Pertussis, Staphylococcus aureus infection, Systemic lupus erythematosus, Coronavirus disease, Renin-angiotensin system, Ferroptosis, Porphyrin and chlorophyll metabolism, Type II diabetes mellitus, Glutathione metabolism,

Downregulated

19

Serum EV

Complement and coagulation cascades, Platelet activation, Coronavirus disease, ECM-receptor interaction, Staphylococcus aureus infection, Neutrophil extracellular trap formation, Focal adhesion, , , ,

Upregulated

Allograft rejection, Staphylococcus aureus infection, Autoimmune thyroid disease, Viral myocarditis, Systemic lupus erythematosus, Pertussis, Complement and coagulation cascades, Dilated cardiomyopathy, Chagas disease, Coronavirus disease,

Downregulated

20

Blood Plasma

Complement and coagulation cascades, Coronavirus disease, Neuroactive ligand-receptor interaction

Upregulated

Complement and coagulation cascades, Staphylococcus aureus infection, Vitamin digestion and absorption, African trypanosomiasis, Fat digestion and absorption, Cholesterol metabolism, PPAR signaling pathway, Platelet activation, Neutrophil extracellular trap formation, Lipid and atherosclerosis,

Downregulated

21

Blood Plasma

Nil

Upregulated

Nil

Downregulated

22

Blood Plasma

PI3K-Akt signaling pathway, ECM-receptor interaction, Growth hormone synthesis, secretion and action, JAK-STAT signaling pathway, Focal adhesion, Cytokine-cytokine receptor interaction, Human papillomavirus infection, Neuroactive ligand-receptor interaction,

Upregulated

Arginine biosynthesis

Downregulated

23

Blood Plasma

ECM-receptor interaction, Staphylococcus aureus infection

Upregulated

Pantothenate and CoA biosynthesis, Complement and coagulation cascades,

Downregulated

24

Blood Plasma

African trypanosomiasis, Malaria, AGE-RAGE signaling pathway in diabetic complications, NF-kappa B signaling pathway, TNF signaling pathway, Leukocyte transendothelial migration, Fluid shear stress and atherosclerosis, Cell adhesion molecules, Lipid and atherosclerosis,

Upregulated

African trypanosomiasis, Graft-versus-host disease, Malaria, Legionellosis, Inflammatory bowel disease, Pertussis, Antigen processing and presentation, Epstein-Barr virus infection, Human T-cell leukemia virus 1 infection, Human cytomegalovirus infection,

Downregulated

25

Blood Plasma

Sphingolipid signaling pathway, Lysosome, Estrogen signaling pathway, Autophagy, Apoptosis, Protein processing in endoplasmic reticulum, Tuberculosis, Diabetic cardiomyopathy

Downregulated

26

Blood Plasma

ECM-receptor interaction

Upregulated

27

Blood Plasma

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration, MAPK signaling pathway

Upregulated

28

Blood Plasma

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

29

Blood Serum

Nil

Upregulated

Nil

Downregulated

30

Blood Serum

Cholesterol metabolism, Thyroid hormone synthesis, Complement and coagulation cascades

Upregulated

Vasopressin-regulated water reabsorption

Downregulated

31

Blood Serum

Complement and coagulation cascades, Staphylococcus aureus infection, Platelet activation, Neutrophil extracellular trap formation, Coronavirus disease

Upregulated

Vitamin digestion and absorption, Fat digestion and absorption, Cholesterol metabolism, African trypanosomiasis, Lipid and atherosclerosis, PPAR signaling pathway, Complement and coagulation cascades, Platelet activation, Phospholipase D signaling pathway,

Downregulated

32

Blood Serum

Nil

Upregulated

Asthma, JAK-STAT signaling pathway, Cytokine-cytokine receptor interaction

Downregulated

33

Blood Serum

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Upregulated

34

Whole Blood

Parkinson disease, MAPK signaling pathway, Alzheimer disease, Pathways of neurodegeneration

Upregulated

Parkinson disease, Alzheimer disease, Pathways of neurodegeneration

Downregulated

Metabolomics

1

Blood plasma

Sphingolipid metabolism

Upregulated

names not identified

Downregulated

2

Blood plasma

names not identified

Upregulated

3

Blood plasma

Citrate cycle (TCA cycle), Arginine biosynthesis

Upregulated

NIL

Downregulated

4

Blood plasma

Nicotinate and nicotinamide metabolism, Tyrosine metabolism

Upregulated

Tryptophan metabolism

Downregulated

5

Blood Plasma

Steroid hormone biosynthesis

Upregulated

NIL

Downregulated

6

Blood Serum

Arginine biosynthesis, Aminoacyl-tRNA biosynthesis, Pantothenate and CoA biosynthesis, beta-Alanine metabolism, Glutathione metabolism, Alanine, aspartate and glutamate metabolism ,Pyrimidine metabolism Phenylalanine, tyrosine and tryptophan biosynthesis, Tyrosine metabolism, D-Glutamine and D-glutamate metabolism, Nitrogen metabolism

Upregulated

Thiamine metabolism ,Taurine and hypotaurine metabolism, Pantothenate and Co biosynthesis, Glutathione metabolism, Glycine, serine and threonine metabolism, Cysteine and methionine metabolism

Downregulated

7

Blood Plasma

Arginine biosynthesis, Butanoate metabolism

Upregulated

Taurine and hypotaurine metabolism, Biotin metabolism, Lysine degradation

Downregulated

8

Blood Plasma

Linoleic acid metabolism, alpha-Linolenic acid metabolism

Upregulated

Glycerophospholipid metabolism, Glycosylphosphatidylinositol (GPI)-anchor biosynthesis

Downregulated

9

Blood Plasma

Valine, leucine and isoleucine biosynthesis, Aminoacyl-tRNA biosynthesis

Upregulated

Biosynthesis of unsaturated fatty acids, Linoleic acid metabolism

Downregulated

10

Blood Plasma

Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism

Upregulated

NIL

Downregulated

11

Plasma EV

names not identified

Upregulated

names not identified

Downregulated

12

Serum EV

names not identified

Upregulated

names not identified

Downregulated

13

Whole blood

Glutathione metabolism

Upregulated

Purine metabolism

Downregulated

14

Whole blood

names not identified

Downregulated

15

Whole blood

NIL

Upregulated

NIL

Downregulated

16

Blood Plasma

Glycerophospholipid metabolism

Upregulated

Biosynthesis of unsaturated fatty acids, Linoleic acid metabolism, Arachidonic acid metabolism, Synthesis and degradation of ketone bodies, Tryptophan metabolism

Downregulated

17

Whole blood

Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism

Upregulated

Biosynthesis of unsaturated fatty acids

Downregulated

18

Blood Plasma

Purine metabolism

Downregulated

19

Blood Plasma

NIL

Upregulated

20

Blood Serum

D-Glutamine and D-glutamate metabolism, Nitrogen metabolism, Arginine biosynthesis

Upregulated

Arginine and proline metabolism

Downregulated

21

Blood Serum

Arginine and proline metabolism, Arginine biosynthesis

Upregulated

Arginine biosynthesis

Downregulated

22

Blood Serum

Histidine metabolism

Upregulated

NIL

Downregulated

23

Blood Serum

Sphingolipid metabolism, Glycerophospholipid metabolism, Arginine and proline metabolism

Upregulated

Arginine biosynthesis

Downregulated

24

Whole blood

Biosynthesis of unsaturated fatty acids

Upregulated

Butanoate metabolism, Alanine, aspartate and glutamate metabolism, Arginine and proline metabolism, Nitrogen metabolism, D-Glutamine and D-glutamate metabolism

Downregulated

25

Blood Serum

Tyrosine metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Ubiquinone and other terpenoid-quinone biosynthesis, Phenylalanine metabolism, Arginine biosynthesis

Upregulated

Tryptophan metabolism, caffeine metabolism

Downregulated

26

Whole blood

Citrate cycle (TCA cycle), Glyoxylate and dicarboxylate metabolism, Pyruvate metabolism, Galactose metabolism,Alanine, aspartate and glutamate metabolism

Downregulated

27

Blood Serum

NIL

Upregulated