PharmaCoNets

PharmaCoNets of Agomelatine (S_PCN: 103.77 )

Agomelatine regulated-network (S_DN: 17.92)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Agomelatine

hsa00040

Pentose and glucuronate interconversions

9.59E-03

P15121, P14550

AKR1B1, AKR1A1

Agomelatine

hsa00071

Fatty acid degradation

3.50E-02

O75521, P00325, P11766, P33121

ECI2, ADH1B, ADH5, ACSL1

Agomelatine

hsa00190

Oxidative phosphorylation

3.97E-04

Q16718, Q13488, P36542, O14521

NDUFA5, TCIRG1, ATP5C1, SDHD

Agomelatine

hsa00512

Mucin type O-glycan biosynthesis

3.78E-02

O95395, Q8N4A0

GCNT3, GALNT4

Agomelatine

hsa00533

Glycosaminoglycan biosynthesis - keratan sulfate

1.91E-02

Q9NY97

B3GNT2

Agomelatine

hsa00561

Glycerolipid metabolism

7.94E-03

P15121, P14550, Q86XP1

AKR1B1, AKR1A1, DGKH

Agomelatine

hsa00601

Glycosphingolipid biosynthesis - lacto and neolacto series

3.78E-02

Q9NY97

B3GNT2

Agomelatine

hsa00630

Glyoxylate and dicarboxylate metabolism

1.32E-02

P40925, P15104

MDH1, GLUL

Agomelatine

hsa00770

Pantothenate and CoA biosynthesis

1.94E-02

O95498, Q9NRN7

VNN2, AASDHPPT

Agomelatine

hsa00830

Retinol metabolism

1.64E-03

P00325, P11766, Q9BPW9, O75911

ADH1B, ADH5, DHRS9, DHRS3

Agomelatine

hsa00920

Sulfur metabolism

4.01E-04

Q16762

TST

Agomelatine

hsa00970

Aminoacyl-tRNA biosynthesis

2.24E-03

O95363, P14868, Q15046

FARS2, DARS, KARS

Agomelatine

hsa01210

2-Oxocarboxylic acid metabolism

1.91E-02

P50213

IDH3A

Agomelatine

hsa03010

Ribosome

1.60E-02

P30050, P40429, P62906, P62917, Q9H0U6, P36578, P05386, P62249, P23396

RPL12, RPL13A, RPL10A, RPL8, MRPL18, RPL4, RPLP1, RPS16, RPS3

Agomelatine

hsa03013

RNA transport

1.58E-05

O14980, Q09161, O14893, P38919, P37198, Q7Z3B4, P35658, P47813, Q14152, P55884, O75822, Q14240, Q9BZI7, Q06787, P51114

XPO1, NCBP1, GEMIN2, EIF4A3, NUP62, NUP54, NUP214, EIF1AX, EIF3A, EIF3B, EIF3J, EIF4A2, UPF3B, FMR1, FXR1

Agomelatine

hsa03020

RNA polymerase

2.94E-07

P24928, P62487, Q9GZM3, P52435

POLR2A, POLR2G, POLR2J2, POLR2J

Agomelatine

hsa03022

Basal transcription factors

4.32E-04

P20226, O00268, Q5H9L4, Q15544

TBP, TAF4, TAF7L, TAF11

Agomelatine

hsa03030

DNA replication

1.48E-02

P49005, P33993, P15927

POLD2, MCM7, RPA2

Agomelatine

hsa03040

Spliceosome

2.00E-08

Q14562, O43143, O60508, P08579, P26368, Q13595, Q07955, Q01130, P84103, Q13243, P11142, Q9Y2W2, O43447, O75643

DHX8, DHX15, CDC40, SNRPB2, U2AF2, TRA2A, SFRS1, SFRS2, SFRS3, SFRS5, HSPA8, WBP11, PPIH, ASCC3L1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q14562	DHX8	ATP-dependent RNA helicase DHX8	0.803
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O43143	DHX15	ATP-dependent RNA helicase DHX15	0.869
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.76
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O60508	CDC40	Pre-mRNA-processing factor 17	0.827
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O60508	CDC40	Pre-mRNA-processing factor 17	-0.812
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.778
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	-0.822
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P26368	U2AF2	Splicing factor U2AF 65 kDa subunit	-0.751
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13595	TRA2A	Transformer-2 protein homolog alpha	-0.74
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.866
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	-0.749
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.835
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.798
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84103	SFRS3	Serine/arginine-rich splicing factor 3	-0.773
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.908
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	-0.822
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.928
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P11142	HSPA8	Heat shock cognate 71 kDa protein	-0.802
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q9Y2W2	WBP11	WW domain-binding protein 11	-0.743
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	0.786
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	-0.766
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O75643	ASCC3L1	U5 small nuclear ribonucleoprotein 200 kDa helicase	0.78
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75643	ASCC3L1	U5 small nuclear ribonucleoprotein 200 kDa helicase	-0.745

Agomelatine

hsa03050

Proteasome

4.83E-02

P55036

PSMD4

Agomelatine

hsa03450

Non-homologous end-joining

4.21E-02

P13010

XRCC5

Agomelatine

hsa04012

ErbB signaling pathway

1.34E-02

P16333, P19174, P42338, P01106

NCK1, PLCG1, PIK3CB, MYC

Agomelatine

hsa04014

Ras signaling pathway

4.75E-05

P42338, P20827, Q9NRA1, P49767, Q13009, Q7LDG7, P0DP23, P62873, P63218, P50151, P19174

PIK3CB, EFNA1, PDGFC, VEGFC, TIAM1, RASGRP2, CALM1, GNB1, GNG5, GNG10, PLCG1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P20827	EFNA1	Ephrin-A1	-0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P20827	EFNA1	Ephrin-A1	0.715
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q9NRA1	PDGFC	Platelet-derived growth factor C	-0.702
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P49767	VEGFC	Vascular endothelial growth factor C	-0.778
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	-0.748
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	0.706
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P0DP23	CALM1	Calmodulin-1	0.826
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.764
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.846
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.799
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766

Agomelatine

hsa04015

Rap1 signaling pathway

5.19E-05

P20827, Q9NRA1, P49767, Q96FS4, P11215, P25116, Q8TEU7, Q13009, Q7LDG7, P42338, P0DP23, P08514, P19174

EFNA1, PDGFC, VEGFC, SIPA1, ITGAM, F2R, RAPGEF6, TIAM1, RASGRP2, PIK3CB, CALM1, ITGA2B, PLCG1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P20827	EFNA1	Ephrin-A1	-0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P20827	EFNA1	Ephrin-A1	0.715
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q9NRA1	PDGFC	Platelet-derived growth factor C	-0.702
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P49767	VEGFC	Vascular endothelial growth factor C	-0.778
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q96FS4	SIPA1	Signal-induced proliferation-associated protein 1	0.728
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P11215	ITGAM	Integrin alpha-M	-0.877
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P11215	ITGAM	Integrin alpha-M	0.817
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P25116	F2R	Proteinase-activated receptor 1	0.783
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	Q8TEU7	RAPGEF6	Rap guanine nucleotide exchange factor 6	-0.727
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	-0.748
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	0.706
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P0DP23	CALM1	Calmodulin-1	0.826
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P08514	ITGA2B	Integrin alpha-IIb	0.941
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766

Agomelatine

hsa04020

Calcium signaling pathway

8.05E-05

P27987, Q96DU7, P21796, Q13557, P21860, P19174, P0DP23, P05141, P12236, P26678, P63092, Q9NRA1, P49767

ITPKB, ITPKC, VDAC1, CAMK2D, ERBB3, PLCG1, CALM1, SLC25A5, SLC25A6, PLN, GNAS, PDGFC, VEGFC

Agomelatine

hsa04022

cGMP-PKG signaling pathway

9.36E-03

P61586, P26678, Q99941, P18848, P05141, P12236

RHOA, PLN, CREBL1, ATF4, SLC25A5, SLC25A6

Agomelatine

hsa04061

Viral protein interaction with cytokine and cytokine receptor

4.48E-02

P09341, P19875, P25024, P25025, P14784

CXCL1, CXCL2, CXCR1, CXCR2, IL2RB

Agomelatine

hsa04062

Chemokine signaling pathway

1.30E-06

P25024, P25025, P09341, P19875, P09769, P07948, P42338, P19174, P62873, P63218, P50151, P43250, Q7LDG7, Q13009, P14598, P42224, P25963, Q8WYR1

CXCR1, CXCR2, CXCL1, CXCL2, FGR, LYN, PIK3CB, PLCG1, GNB1, GNG5, GNG10, GRK6, RASGRP2, TIAM1, NCF1, STAT1, NFKBIA, PIK3R5

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
Q13547	HDAC1	Histone deacetylase 1	P25024	CXCR1	C-X-C chemokine receptor type 1	-0.803
Q13547	HDAC1	Histone deacetylase 1	P25025	CXCR2	C-X-C chemokine receptor type 2	-0.719
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P09769	FGR	Tyrosine-protein kinase Fgr	0.796
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P07948	LYN	Tyrosine-protein kinase Lyn	-0.852
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P07948	LYN	Tyrosine-protein kinase Lyn	0.971
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.764
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.846
Q13547	HDAC1	Histone deacetylase 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.864
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.799
Q13547	HDAC1	Histone deacetylase 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.716
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P43250	GRK6	G protein-coupled receptor kinase 6	-0.775
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43250	GRK6	G protein-coupled receptor kinase 6	0.818
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	-0.748
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	0.706
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14598	NCF1	Neutrophil cytosol factor 1	0.755
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q8WYR1	PIK3R5	Phosphoinositide 3-kinase regulatory subunit 5	0.752

Agomelatine

hsa04064

NF-kappa B signaling pathway

7.84E-04

O00463, P14778, P01584, P01375, P19174, Q04759, Q13077, Q16548, P06239, Q8WV28, P24522, P09341, P19875, Q06643, Q9NQC7

TRAF5, IL1R1, IL1B, TNF, PLCG1, PRKCQ, TRAF1, BCL2A1, LCK, BLNK, GADD45A, CXCL1, CXCL2, LTB, CYLD

Agomelatine

hsa04070

Phosphatidylinositol signaling system

1.12E-02

P19174, P0DP23, P42338, P23743, P27987

PLCG1, CALM1, PIK3CB, DGKA, ITPKB

Agomelatine

hsa04071

Sphingolipid signaling pathway

4.56E-02

Q9H228, P01375, Q13362, Q9BX95, Q16539, P10415

EDG8, TNF, PPP2R5C, SGPP1, MAPK14, BCL2

Agomelatine

hsa04072

Phospholipase D signaling pathway

5.49E-03

P42338, P43657, P25024, P25025, P19174, Q14344, P23743, Q9NRA1

PIK3CB, P2RY5, CXCR1, CXCR2, PLCG1, GNA13, DGKA, PDGFC

Agomelatine

hsa04120

Ubiquitin mediated proteolysis

4.82E-03

Q9UBT2, Q14669

SAE2, TRIP12

Agomelatine

hsa04122

Sulfur relay system

4.01E-04

Q16762

TST

Agomelatine

hsa04146

Peroxisome

4.83E-02

O96011, P56589, Q9UKG9, O75521

PEX11B, PEX3, CROT, ECI2

Agomelatine

hsa04151

PI3K-Akt signaling pathway

5.24E-05

P42338, P21860, P43657, P01106, P27348, P20827, O14944, Q9NRA1, P49767, P07900, P08238, Q15831, Q8WYR1, P62873, P63218, P50151, O15335, Q13751, P22105, P14784, P01568, Q99941, P18848, P30281, O95988

PIK3CB, ERBB3, P2RY5, MYC, YWHAQ, EFNA1, EREG, PDGFC, VEGFC, HSP90AA1, HSP90AB1, STK11, PIK3R5, GNB1, GNG5, GNG10, CHAD, LAMB3, TNXB, IL2RB, IFNA21, CREBL1, ATF4, CCND3, TCL1B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P40926	MDH2	Malate dehydrogenase, mitochondrial	P21860	ERBB3	Receptor tyrosine-protein kinase erbB-3	-0.731
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P01106	MYC	Myc proto-oncogene protein	0.719
P40926	MDH2	Malate dehydrogenase, mitochondrial	P27348	YWHAQ	14-3-3 protein theta	0.711
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P20827	EFNA1	Ephrin-A1	-0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P20827	EFNA1	Ephrin-A1	0.715
P40926	MDH2	Malate dehydrogenase, mitochondrial	O14944	EREG	Proepiregulin [Cleaved into: Epiregulin	-0.778
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q9NRA1	PDGFC	Platelet-derived growth factor C	-0.702
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P49767	VEGFC	Vascular endothelial growth factor C	-0.778
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P40926	MDH2	Malate dehydrogenase, mitochondrial	P07900	HSP90AA1	Heat shock protein HSP 90-alpha	0.718
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.926
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P40926	MDH2	Malate dehydrogenase, mitochondrial	Q15831	STK11	Serine/threonine-protein kinase STK11	0.731
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q8WYR1	PIK3R5	Phosphoinositide 3-kinase regulatory subunit 5	0.752
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.764
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.846
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.799
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O15335	CHAD	Chondroadherin	-0.704
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O15335	CHAD	Chondroadherin	0.795
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13751	LAMB3	Laminin subunit beta-3	0.844
P40926	MDH2	Malate dehydrogenase, mitochondrial	P22105	TNXB	Tenascin-X	0.802
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.912
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P01568	IFNA21	Interferon alpha-21	-0.701
P40926	MDH2	Malate dehydrogenase, mitochondrial	Q99941	CREBL1	Cyclic AMP-dependent transcription factor ATF-6 beta	0.802
P40926	MDH2	Malate dehydrogenase, mitochondrial	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.781
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743
P40926	MDH2	Malate dehydrogenase, mitochondrial	O95988	TCL1B	T-cell leukemia/lymphoma protein 1B	0.719

Agomelatine

hsa04213

Longevity regulating pathway - multiple species

3.85E-02

P42338, Q9Y4H2, P11142, Q13547

PIK3CB, IRS2, HSPA8, HDAC1

Agomelatine

hsa04217

Necroptosis

2.87E-03

P01568, Q13489, P42224, P08238, Q6FI13, Q93077, O43633, Q08752

IFNA21, BIRC3, STAT1, HSP90AB1, H2AC18; H2AC19, HIST1H2AC, CHMP2A, PPID

Agomelatine

hsa04261

Adrenergic signaling in cardiomyocytes

3.12E-02

P63092, Q99941, P18848, P26678, Q13557

GNAS, CREBL1, ATF4, PLN, CAMK2D

Agomelatine

hsa04330

Notch signaling pathway

2.77E-02

Q92542, P49768

NCSTN, PSEN1

Agomelatine

hsa04340

Hedgehog signaling pathway

3.46E-02

P49841, P22694, Q13635, P10415

GSK3B, PRKACB, PTCH1, BCL2

Agomelatine

hsa04360

Axon guidance

3.83E-03

P16333, P20827, O95631, P42338, P07332, P19174

NCK1, EFNA1, NTN1, PIK3CB, FES, PLCG1

Agomelatine

hsa04371

Apelin signaling pathway

9.23E-05

P62873, P63218, P50151, Q8WYR1, Q13370, Q14814, Q14344, Q13485, P84022, P0DP23

GNB1, GNG5, GNG10, PIK3R5, PDE3B, MEF2D, GNA13, SMAD4, SMAD3, CALM1

Agomelatine

hsa04380

Osteoclast differentiation

2.05E-03

Q9NQC7, Q9UQC2, Q16539, P23458, P06239, P01584, P14778, O75015, Q8WV28, P01375, Q15080, P78324

CYLD, GAB2, MAPK14, JAK1, LCK, IL1B, IL1R1, FCGR3B, BLNK, TNF, NCF4, SIRPA

Agomelatine

hsa04390

Hippo signaling pathway

4.35E-02

P63261, O15105

ACTG1, SMAD7

Agomelatine

hsa04512

ECM-receptor interaction

3.73E-02

P07359, P08514

GP1BA, ITGA2B

Agomelatine

hsa04514

Cell adhesion molecules

8.19E-03

P16109, P56750, O00501

SELP, CLDN17, CLDN5

Agomelatine

hsa04530

Tight junction

1.93E-05

Q8TEU7, P63261, P16989, P56750, O00501, Q92974, Q14247

RAPGEF6, ACTG1, CSDA, CLDN17, CLDN5, ARHGEF2, CTTN

Agomelatine

hsa04610

Complement and coagulation cascades

4.47E-02

P25116, P09871

F2R, C1S

Agomelatine

hsa04611

Platelet activation

5.18E-05

P25116, P08514, Q15746, Q8WYR1, P07359

F2R, ITGA2B, MYLK, PIK3R5, GP1BA

Agomelatine

hsa04612

Antigen processing and presentation

2.40E-02

P13765, P48382, P26715, P26717, Q13241, O43908, P01732, P01375

HLA-DOB, RFX5, KLRC1, KLRC2, KLRD1, KLRC4, CD8A, TNF

Agomelatine

hsa04613

Neutrophil extracellular trap formation

7.00E-05

P42338, P19174, P16109, P11215, O60603, P05164, P08246, Q9UM07, Q13547, Q92769, P0C0S5, Q6FI13, P62807, Q93079, O60814, P21796, P14598, Q15080, P20160, P08311, O75015, P21730, P08514, P21462, P07359, O43315, Q16539

PIK3CB, PLCG1, SELP, ITGAM, TLR2, MPO, ELA2, PADI4, HDAC1, HDAC2, H2AFZ, H2AC18; H2AC19, HIST1H2BC, H2BC9, H2BC12, VDAC1, NCF1, NCF4, AZU1, CTSG, FCGR3B, C5AR1, ITGA2B, FPR1, GP1BA, AQP9, MAPK14

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P16109	SELP	P-selectin	0.819
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P11215	ITGAM	Integrin alpha-M	-0.877
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60603	TLR2	Toll-like receptor 2	0.842
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P05164	MPO	Myeloperoxidase	0.719
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08246	ELA2	Neutrophil elastase	0.702
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.813
P14780	MMP9	Matrix metalloproteinase-9	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.9
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13547	HDAC1	Histone deacetylase 1	-0.7
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13547	HDAC1	Histone deacetylase 1	0.701
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q92769	HDAC2	Histone deacetylase 2	-0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P0C0S5	H2AFZ	Histone H2A.Z	0.785
P14780	MMP9	Matrix metalloproteinase-9	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.74
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	-0.703
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	-0.703
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q93079	H2BC9	Histone H2B type 1-H	0.756
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	O60814	H2BC12	Histone H2B type 1-K	0.783
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P21796	VDAC1	Voltage-dependent anion-selective channel protein 1	0.72
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14598	NCF1	Neutrophil cytosol factor 1	0.755
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q15080	NCF4	Neutrophil cytosol factor 4	0.762
P14780	MMP9	Matrix metalloproteinase-9	Q15080	NCF4	Neutrophil cytosol factor 4	0.869
P14780	MMP9	Matrix metalloproteinase-9	P20160	AZU1	Azurocidin	0.734
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08311	CTSG	Cathepsin G	0.744
P14780	MMP9	Matrix metalloproteinase-9	P08311	CTSG	Cathepsin G	0.79
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.92
P14780	MMP9	Matrix metalloproteinase-9	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.928
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	0.983
P14780	MMP9	Matrix metalloproteinase-9	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	0.942
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P08514	ITGA2B	Integrin alpha-IIb	0.941
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P21462	FPR1	fMet-Leu-Phe receptor	0.839
P14780	MMP9	Matrix metalloproteinase-9	P21462	FPR1	fMet-Leu-Phe receptor	0.912
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P07359	GP1BA	Platelet glycoprotein Ib alpha chain	0.876
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O43315	AQP9	Aquaporin-9	0.934
P14780	MMP9	Matrix metalloproteinase-9	O43315	AQP9	Aquaporin-9	0.837
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778

Agomelatine

hsa04614

Renin-angiotensin system

8.01E-03

P15144, P10619, P08311, O75787

ANPEP, CTSA, CTSG, ATP6AP2

Agomelatine

hsa04620

Toll-like receptor signaling pathway

4.00E-02

P01568, P42224, P25963, P42338

IFNA21, STAT1, NFKBIA, PIK3CB

Agomelatine

hsa04621

NOD-like receptor signaling pathway

2.62E-02

Q16539, Q14643, P10599, Q9H1Y0, P43490, O00463, P10415, Q05823, P01375, P09341, P12838

MAPK14, ITPR1, TXN, ATG5, PBEF1, TRAF5, BCL2, RNASEL, TNF, CXCL1, DEFA4

Agomelatine

hsa04623

Cytosolic DNA-sensing pathway

1.85E-03

P01568, P25963

IFNA21, NFKBIA

Agomelatine

hsa04625

C-type lectin receptor signaling pathway

5.57E-04

Q9ULY5, P01584, Q9NQC7, P42224, P20749, P25963, Q14643, P01375, Q13191, P42338, P0DP24, P0DP23, Q16539

CLEC4E, IL1B, CYLD, STAT1, BCL3, NFKBIA, ITPR1, TNF, CBLB, PIK3CB, CALM2, CALM1, MAPK14

Agomelatine

hsa04640

Hematopoietic cell lineage

2.62E-03

P13612, P14778, P27930, P11215, P15144, P11836, P25063, P07766, P09693, P01732, P09564, P13765, P01375, P01584

ITGA4, IL1R1, IL1R2, ITGAM, ANPEP, MS4A1, CD24, CD3E, CD3G, CD8A, CD7, HLA-DOB, TNF, IL1B

Agomelatine

hsa04650

Natural killer cell mediated cytotoxicity

4.85E-04

P19174, P01375, P78314, P06239, O60880, P20963, P42338, Q13241, P26718, O14931, O75015, P26717, P26715

PLCG1, TNF, SH3BP2, LCK, SH2D1A, CD247, PIK3CB, KLRD1, KLRK1, NCR3, FCGR3B, KLRC2, KLRC1

Agomelatine

hsa04657

IL-17 signaling pathway

1.49E-03

O00463, Q16539, P49841, P09341, P14780, P80188, P01375, P01584

TRAF5, MAPK14, GSK3B, CXCL1, MMP9, LCN2, TNF, IL1B

Agomelatine

hsa04658

Th1 and Th2 cell differentiation

4.29E-08

P25963, Q04759, P07766, P20963, P09693, Q16539, P19174, P06239, P42224, Q14765, P23771, Q9UL17, P14784, P13765, P23458, Q13761

NFKBIA, PRKCQ, CD3E, CD247, CD3G, MAPK14, PLCG1, LCK, STAT1, STAT4, GATA3, TBX21, IL2RB, HLA-DOB, JAK1, RUNX3

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P14780	MMP9	Matrix metalloproteinase-9	Q04759	PRKCQ	Protein kinase C theta type	-0.787
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.839
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P14780	MMP9	Matrix metalloproteinase-9	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.745
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P14780	MMP9	Matrix metalloproteinase-9	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.719
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.777
P14780	MMP9	Matrix metalloproteinase-9	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.861
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.763
P14780	MMP9	Matrix metalloproteinase-9	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.747
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9UL17	TBX21	T-box transcription factor TBX21	-0.872
P14780	MMP9	Matrix metalloproteinase-9	Q9UL17	TBX21	T-box transcription factor TBX21	-0.808
Q13547	HDAC1	Histone deacetylase 1	Q9UL17	TBX21	T-box transcription factor TBX21	0.817
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.912
Q13547	HDAC1	Histone deacetylase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.816
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13761	RUNX3	Runt-related transcription factor 3	0.804
Q13547	HDAC1	Histone deacetylase 1	Q13761	RUNX3	Runt-related transcription factor 3	0.884

Agomelatine

hsa04659

Th17 cell differentiation

6.35E-07

P25963, Q04759, Q16539, P19174, P06239, P42224, P14784, P13765, P14778, Q9UL17, P23771, P84022, Q13485, P01584, P08238, P07766, P09693, P20963, P23458

NFKBIA, PRKCQ, MAPK14, PLCG1, LCK, STAT1, IL2RB, HLA-DOB, IL1R1, TBX21, GATA3, SMAD3, SMAD4, IL1B, HSP90AB1, CD3E, CD3G, CD247, JAK1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.912
Q13547	HDAC1	Histone deacetylase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.816
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14778	IL1R1	Interleukin-1 receptor type 1	0.766
Q13547	HDAC1	Histone deacetylase 1	P14778	IL1R1	Interleukin-1 receptor type 1	-0.854
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14778	IL1R1	Interleukin-1 receptor type 1	0.764
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9UL17	TBX21	T-box transcription factor TBX21	-0.872
Q13547	HDAC1	Histone deacetylase 1	Q9UL17	TBX21	T-box transcription factor TBX21	0.817
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.763
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.725
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.746
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.926
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.839
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	-0.838
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757

Agomelatine

hsa04660

T cell receptor signaling pathway

2.55E-06

P01375, Q9UDY8, Q04759, P42338, O95267, Q08881, P19174, P07766, P20963, P09693, P01732, Q13191, P06239, Q16539, P49841

TNF, MALT1, PRKCQ, PIK3CB, RASGRP1, ITK, PLCG1, CD3E, CD247, CD3G, CD8A, CBLB, LCK, MAPK14, GSK3B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P14780	MMP9	Matrix metalloproteinase-9	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	-0.767
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P14780	MMP9	Matrix metalloproteinase-9	Q04759	PRKCQ	Protein kinase C theta type	-0.787
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.852
P14780	MMP9	Matrix metalloproteinase-9	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.792
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.866
P14780	MMP9	Matrix metalloproteinase-9	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.855
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P14780	MMP9	Matrix metalloproteinase-9	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.745
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P14780	MMP9	Matrix metalloproteinase-9	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.719
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.781
P14780	MMP9	Matrix metalloproteinase-9	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.742
Q13547	HDAC1	Histone deacetylase 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.816
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.803
P14780	MMP9	Matrix metalloproteinase-9	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.793
Q13547	HDAC1	Histone deacetylase 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	0.806
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.812
P14780	MMP9	Matrix metalloproteinase-9	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.75

Agomelatine

hsa04662

B cell receptor signaling pathway

5.25E-04

P25963, P42338, P60033, P07948, P21854, Q8N149

NFKBIA, PIK3CB, CD81, LYN, CD72, LILRA2

Agomelatine

hsa04664

Fc epsilon RI signaling pathway

8.73E-04

P42338, P07948, P19174, P09917

PIK3CB, LYN, PLCG1, ALOX5

Agomelatine

hsa04666

Fc gamma R-mediated phagocytosis

2.92E-02

P07948, P42338, P19174, P14598

LYN, PIK3CB, PLCG1, NCF1

Agomelatine

hsa04713

Circadian entrainment

4.00E-02

P0DP23, P62873, P63218, P50151

CALM1, GNB1, GNG5, GNG10

Agomelatine

hsa04721

Synaptic vesicle cycle

3.15E-02

Q13488, P31645

TCIRG1, SLC6A4

Agomelatine

hsa04724

Glutamatergic synapse

2.92E-02

P62873, P63218, P50151, P15104

GNB1, GNG5, GNG10, GLUL

Agomelatine

hsa04725

Cholinergic synapse

2.92E-02

P62873, P63218, P50151, P42338

GNB1, GNG5, GNG10, PIK3CB

Agomelatine

hsa04727

GABAergic synapse

8.14E-03

P62873, P63218, P50151, P15104

GNB1, GNG5, GNG10, GLUL

Agomelatine

hsa04740

Olfactory transduction

2.52E-02

Q9H255

OR51E2

Agomelatine

hsa04742

Taste transduction

1.01E-02

P30939

HTR1F

Agomelatine

hsa04744

Phototransduction

1.32E-02

P62873, P0DP23

GNB1, CALM1

Agomelatine

hsa04750

Inflammatory mediator regulation of TRP channels

3.62E-05

P14778, P01584, P51828, P22694, Q16539, P19174, P42338, Q14643, P24723, Q04759, P0DP24, P0DP23

IL1R1, IL1B, ADCY7, PRKACB, MAPK14, PLCG1, PIK3CB, ITPR1, PRKCH, PRKCQ, CALM2, CALM1

Agomelatine

hsa04810

Regulation of actin cytoskeleton

2.63E-03

P12814, Q15746, Q13009, P42338, P08514, P11215, Q14344, Q9NRA1, P25116

ACTN1, MYLK, TIAM1, PIK3CB, ITGA2B, ITGAM, GNA13, PDGFC, F2R

Agomelatine

hsa04911

Insulin secretion

4.47E-03

P63092, Q99941, P18848, Q13557

GNAS, CREBL1, ATF4, CAMK2D

Agomelatine

hsa04912

GnRH signaling pathway

4.33E-02

P51828, Q16539, Q9Y6R4, Q14643, P0DP24, P22694

ADCY7, MAPK14, MAP3K4, ITPR1, CALM2, PRKACB

Agomelatine

hsa04914

Progesterone-mediated oocyte maturation

4.00E-02

P42338, Q13370, P30304, P08238

PIK3CB, PDE3B, CDC25A, HSP90AB1

Agomelatine

hsa04923

Regulation of lipolysis in adipocytes

2.24E-02

P07550, P42338, Q9Y4H2

ADRB2, PIK3CB, IRS2

Agomelatine

hsa04924

Renin secretion

4.38E-02

P07550

ADRB2

Agomelatine

hsa04925

Aldosterone synthesis and secretion

1.68E-02

Q99941, P18848, P63092, Q13557

CREBL1, ATF4, GNAS, CAMK2D

Agomelatine

hsa04926

Relaxin signaling pathway

8.74E-03

P25963, P42338, P62873, P63218, P50151, P49767

NFKBIA, PIK3CB, GNB1, GNG5, GNG10, VEGFC

Agomelatine

hsa04927

Cortisol synthesis and secretion

2.40E-02

Q99941, P18848, P63092

CREBL1, ATF4, GNAS

Agomelatine

hsa04928

Parathyroid hormone synthesis, secretion and action

2.33E-02

P63092, P61586, Q99941, P18848

GNAS, RHOA, CREBL1, ATF4

Agomelatine

hsa04933

AGE-RAGE signaling pathway in diabetic complications

3.21E-02

P84022, Q13485, P42338, P49767, P19174

SMAD3, SMAD4, PIK3CB, VEGFC, PLCG1

Agomelatine

hsa04934

Cushing syndrome

1.37E-03

Q99941, P18848, P63092, O15169, Q13557

CREBL1, ATF4, GNAS, AXIN1, CAMK2D

Agomelatine

hsa04972

Pancreatic secretion

1.31E-02

Q08828, P62491

ADCY1, RAB11A

Agomelatine

hsa04973

Carbohydrate digestion and absorption

1.29E-02

O43451, P42338

MGAM, PIK3CB

Agomelatine

hsa05010

Alzheimer disease

1.36E-02

Q92542, O15239, P05496, P18848, O15169, P05141, P12236, P43686, P62195

NCSTN, NDUFA1, ATP5G1, ATF4, AXIN1, SLC25A5, SLC25A6, PSMC4, PSMC5

Agomelatine

hsa05012

Parkinson disease

5.04E-04

O15239, P05496, P05141, P12236, P21796, P60604, P63092, P18848, P43686, P62195, P19174, P0DP23, Q13557, Q71U36, Q13509

NDUFA1, ATP5G1, SLC25A5, SLC25A6, VDAC1, UBE2G2, GNAS, ATF4, PSMC4, PSMC5, PLCG1, CALM1, CAMK2D, TUBA1A, TUBB3

Agomelatine

hsa05014

Amyotrophic lateral sclerosis

3.98E-03

P01375, P20333, O15239, Q16718, O14521, P36542, P05496, P18848, P43686, P62195, P51991, P09651, Q7Z3B4, P35658, P43243, Q09161, Q16629

TNF, TNFRSF1B, NDUFA1, NDUFA5, SDHD, ATP5C1, ATP5G1, ATF4, PSMC4, PSMC5, HNRPA3, HNRNPA1, NUP54, NUP214, MATR3, NCBP1, SFRS7

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	P01375	TNF	Tumor necrosis factor	-0.76
P40926	MDH2	Malate dehydrogenase, mitochondrial	P20333	TNFRSF1B	Tumor necrosis factor receptor superfamily member 1B	0.772
P40926	MDH2	Malate dehydrogenase, mitochondrial	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.747
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	Q16718	NDUFA5	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5	0.733
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	O14521	SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	0.702
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	P36542	ATP5C1	ATP synthase subunit gamma, mitochondrial	0.792
P40926	MDH2	Malate dehydrogenase, mitochondrial	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.718
P40926	MDH2	Malate dehydrogenase, mitochondrial	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.781
P40926	MDH2	Malate dehydrogenase, mitochondrial	P43686	PSMC4	26S proteasome regulatory subunit 6B	0.835
P40926	MDH2	Malate dehydrogenase, mitochondrial	P62195	PSMC5	26S proteasome regulatory subunit 8	0.721
P40926	MDH2	Malate dehydrogenase, mitochondrial	P51991	HNRPA3	Heterogeneous nuclear ribonucleoprotein A3	0.802
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	P09651	HNRNPA1	Heterogeneous nuclear ribonucleoprotein A1	0.801
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	Q7Z3B4	NUP54	Nucleoporin p54	0.883
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	P35658	NUP214	Nuclear pore complex protein Nup214	-0.708
P40926	MDH2	Malate dehydrogenase, mitochondrial	P35658	NUP214	Nuclear pore complex protein Nup214	-0.845
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	P43243	MATR3	Matrin-3	0.724
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	Q09161	NCBP1	Nuclear cap-binding protein subunit 1	0.771
Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	Q16629	SFRS7	Serine/arginine-rich splicing factor 7	0.801

Agomelatine

hsa05016

Huntington disease

2.46E-05

Q9GZM3, P52435, Q9NYC9

POLR2J2, POLR2J, DNAH9

Agomelatine

hsa05020

Prion disease

1.15E-02

P46531, O15239, P05496, P18848, P05141, P12236, P43686, P62195, Q99941

NOTCH1, NDUFA1, ATP5G1, ATF4, SLC25A5, SLC25A6, PSMC4, PSMC5, CREBL1

Agomelatine

hsa05022

Pathways of neurodegeneration - multiple diseases

1.57E-02

O15239, P05496, P18848, P05141, P12236, P20333, O15169, Q13557, P43686, P62195

NDUFA1, ATP5G1, ATF4, SLC25A5, SLC25A6, TNFRSF1B, AXIN1, CAMK2D, PSMC4, PSMC5

Agomelatine

hsa05030

Cocaine addiction

2.40E-02

P63092, Q99941, P18848

GNAS, CREBL1, ATF4

Agomelatine

hsa05031

Amphetamine addiction

4.47E-03

Q13557, P63092, Q99941, P18848

CAMK2D, GNAS, CREBL1, ATF4

Agomelatine

hsa05032

Morphine addiction

7.60E-03

P62873, P63218, P50151, Q13370, P43250

GNB1, GNG5, GNG10, PDE3B, GRK6

Agomelatine

hsa05034

Alcoholism

6.32E-03

Q13547, P0DP23, P62873, P63218, P50151, P62807, Q93079

HDAC1, CALM1, GNB1, GNG5, GNG10, HIST1H2BC, H2BC9

Agomelatine

hsa05100

Bacterial invasion of epithelial cells

4.50E-02

Q92529

SHC3

Agomelatine

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

2.78E-03

P09341, P19875, P19174, P25024, P25025

CXCL1, CXCL2, PLCG1, CXCR1, CXCR2

Agomelatine

hsa05130

Pathogenic Escherichia coli infection

7.39E-03

Q14247, P56750, O00501, P25116

CTTN, CLDN17, CLDN5, F2R

Agomelatine

hsa05132

Salmonella infection

2.36E-02

P25963, P08238, P01106, P42338, O75369, Q71U36, Q13509, P49754

NFKBIA, HSP90AB1, MYC, PIK3CB, FLNB, TUBA1A, TUBB3, VPS41

Agomelatine

hsa05133

Pertussis

2.41E-02

P09871, Q02556

C1S, IRF8

Agomelatine

hsa05134

Legionellosis

1.29E-02

P11215, P11142, P09341, P19875

ITGAM, HSPA8, CXCL1, CXCL2

Agomelatine

hsa05140

Leishmaniasis

9.04E-05

P13612, O75015, P14598, P23458, P42224, P13765, O60603, P25963, P01375, P01584, P29350, Q16539, Q15080

ITGA4, FCGR3B, NCF1, JAK1, STAT1, HLA-DOB, TLR2, NFKBIA, TNF, IL1B, PTPN6, MAPK14, NCF4

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13612	ITGA4	Integrin alpha-4	-0.797
P14780	MMP9	Matrix metalloproteinase-9	P13612	ITGA4	Integrin alpha-4	-0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.92
P14780	MMP9	Matrix metalloproteinase-9	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.928
P09960	LTA4H	Leukotriene A-4 hydrolase	P14598	NCF1	Neutrophil cytosol factor 1	0.798
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
P09960	LTA4H	Leukotriene A-4 hydrolase	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.787
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60603	TLR2	Toll-like receptor 2	0.842
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
P09960	LTA4H	Leukotriene A-4 hydrolase	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.768
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
P09960	LTA4H	Leukotriene A-4 hydrolase	P29350	PTPN6	Tyrosine-protein phosphatase non-receptor type 6	0.808
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q15080	NCF4	Neutrophil cytosol factor 4	0.762
P14780	MMP9	Matrix metalloproteinase-9	Q15080	NCF4	Neutrophil cytosol factor 4	0.869
P09960	LTA4H	Leukotriene A-4 hydrolase	Q15080	NCF4	Neutrophil cytosol factor 4	0.758

Agomelatine

hsa05144

Malaria

2.43E-02

P60033, O60603, P01375, P35443, P01584, P26718

CD81, TLR2, TNF, THBS4, IL1B, KLRK1

Agomelatine

hsa05146

Amoebiasis

2.36E-05

P01584, P09341, P19875, P14778, P27930, P01375, O60603, P42338, P11215, P05089, P22694, P12814, P08311

IL1B, CXCL1, CXCL2, IL1R1, IL1R2, TNF, TLR2, PIK3CB, ITGAM, ARG1, PRKACB, ACTN1, CTSG

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09341	CXCL1	Growth-regulated alpha protein	0.788
P14780	MMP9	Matrix metalloproteinase-9	P09341	CXCL1	Growth-regulated alpha protein	0.771
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14778	IL1R1	Interleukin-1 receptor type 1	0.766
Q13547	HDAC1	Histone deacetylase 1	P14778	IL1R1	Interleukin-1 receptor type 1	-0.854
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P27930	IL1R2	Interleukin-1 receptor type 2	0.926
P14780	MMP9	Matrix metalloproteinase-9	P27930	IL1R2	Interleukin-1 receptor type 2	0.851
Q13547	HDAC1	Histone deacetylase 1	P27930	IL1R2	Interleukin-1 receptor type 2	-0.837
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60603	TLR2	Toll-like receptor 2	0.842
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
Q13547	HDAC1	Histone deacetylase 1	P11215	ITGAM	Integrin alpha-M	-0.751
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P05089	ARG1	Arginase-1	0.848
P14780	MMP9	Matrix metalloproteinase-9	P05089	ARG1	Arginase-1	0.881
Q13547	HDAC1	Histone deacetylase 1	P05089	ARG1	Arginase-1	-0.769
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.772
P14780	MMP9	Matrix metalloproteinase-9	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.826
Q13547	HDAC1	Histone deacetylase 1	P12814	ACTN1	Alpha-actinin-1	-0.887
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08311	CTSG	Cathepsin G	0.744
P14780	MMP9	Matrix metalloproteinase-9	P08311	CTSG	Cathepsin G	0.79

Agomelatine

hsa05150

Staphylococcus aureus infection

4.02E-03

P21462, O75015, Q14532, P59665, P59666, P12838

FPR1, FCGR3B, KRT32, DEFA1; DEFA1B, DEFA3, DEFA4

Agomelatine

hsa05160

Hepatitis C

3.16E-02

P52630, P60033, Q9NZJ5, P49841

STAT2, CD81, EIF2AK3, GSK3B

Agomelatine

hsa05162

Measles

1.84E-02

P01568, P25963, P42224, P14784, P07766, P42338, P11142

IFNA21, NFKBIA, STAT1, IL2RB, CD3E, PIK3CB, HSPA8

Agomelatine

hsa05163

Human cytomegalovirus infection

4.19E-04

P42338, P25963, P62873, P63218, P50151, P0DP23, Q14344, P01106, P30101, P01568

PIK3CB, NFKBIA, GNB1, GNG5, GNG10, CALM1, GNA13, MYC, PDIA3, IFNA21

Agomelatine

hsa05167

Kaposi sarcoma-associated herpesvirus infection

7.49E-05

P01568, P42224, P25963, P42338, P62873, P63218, P50151, P19174, P07948, P01106, P0DP23

IFNA21, STAT1, NFKBIA, PIK3CB, GNB1, GNG5, GNG10, PLCG1, LYN, MYC, CALM1

Agomelatine

hsa05168

Herpes simplex virus 1 infection

6.47E-04

P25963, P01568, Q05823, P42224, Q07955, Q01130, Q13243, Q13489, P30101, P42338, Q13398, Q9HCX3, P52738, O75820, Q9UDV6

NFKBIA, IFNA21, RNASEL, STAT1, SFRS1, SFRS2, SFRS5, BIRC3, PDIA3, PIK3CB, ZNF211, ZNF304, ZNF140, ZNF189, ZNF212

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P09960	LTA4H	Leukotriene A-4 hydrolase	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.768
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P01568	IFNA21	Interferon alpha-21	-0.701
P09960	LTA4H	Leukotriene A-4 hydrolase	P01568	IFNA21	Interferon alpha-21	-0.764
P09960	LTA4H	Leukotriene A-4 hydrolase	Q05823	RNASEL	2-5A-dependent ribonuclease	0.752
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P09960	LTA4H	Leukotriene A-4 hydrolase	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.787
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.866
P09960	LTA4H	Leukotriene A-4 hydrolase	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.732
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.835
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.908
P09960	LTA4H	Leukotriene A-4 hydrolase	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.819
P09960	LTA4H	Leukotriene A-4 hydrolase	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.721
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P30101	PDIA3	Protein disulfide-isomerase A3	0.896
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13398	ZNF211	Zinc finger protein 211	0.891
P09960	LTA4H	Leukotriene A-4 hydrolase	Q13398	ZNF211	Zinc finger protein 211	0.729
P09960	LTA4H	Leukotriene A-4 hydrolase	Q9HCX3	ZNF304	Zinc finger protein 304	-0.746
P09960	LTA4H	Leukotriene A-4 hydrolase	P52738	ZNF140	Zinc finger protein 140	-0.724
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O75820	ZNF189	Zinc finger protein 189	-0.749
P09960	LTA4H	Leukotriene A-4 hydrolase	O75820	ZNF189	Zinc finger protein 189	-0.722
P09960	LTA4H	Leukotriene A-4 hydrolase	Q9UDV6	ZNF212	Zinc finger protein 212	0.824

Agomelatine

hsa05169

Epstein-Barr virus infection

1.08E-03

P01106, Q13547, P25963, P42338, P07948, P30101, Q13761, O75293, P42224, P01568, P07766

MYC, HDAC1, NFKBIA, PIK3CB, LYN, PDIA3, RUNX3, GADD45B, STAT1, IFNA21, CD3E

Agomelatine

hsa05170

Human immunodeficiency virus 1 infection

3.24E-03

P42338, P62873, P63218, P50151, P0DP23, P30101, P01568, P25963, P19174, P07766

PIK3CB, GNB1, GNG5, GNG10, CALM1, PDIA3, IFNA21, NFKBIA, PLCG1, CD3E

Agomelatine

hsa05200

Pathways in cancer

7.17E-05

Q13751, P42338, P08238, P42224, P25963, P19174, P01106, P43246, P84022, Q13485, Q13547, P30281, P49767, P43657, P62873, P63218, P50151, Q14344, Q7LDG7, O75293, P0DP23, P01568, P14784

LAMB3, PIK3CB, HSP90AB1, STAT1, NFKBIA, PLCG1, MYC, MSH2, SMAD3, SMAD4, HDAC1, CCND3, VEGFC, P2RY5, GNB1, GNG5, GNG10, GNA13, RASGRP2, GADD45B, CALM1, IFNA21, IL2RB

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13751	LAMB3	Laminin subunit beta-3	0.844
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.926
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P01106	MYC	Myc proto-oncogene protein	0.719
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P43246	MSH2	DNA mismatch repair protein Msh2	0.887
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43246	MSH2	DNA mismatch repair protein Msh2	-0.811
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.725
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.746
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q13547	HDAC1	Histone deacetylase 1	0.701
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13547	HDAC1	Histone deacetylase 1	-0.754
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P49767	VEGFC	Vascular endothelial growth factor C	-0.778
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.764
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.846
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.799
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P40925	MDH1	Malate dehydrogenase, cytoplasmic	Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	-0.735
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	0.87
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P40925	MDH1	Malate dehydrogenase, cytoplasmic	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.847
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	0.731
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P0DP23	CALM1	Calmodulin-1	0.826
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P01568	IFNA21	Interferon alpha-21	-0.701
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.912
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835

Agomelatine

hsa05202

Transcriptional misregulation in cancer

5.26E-04

P17844, P14780, P27930, Q15744, Q16548, Q13077, P35226, P05164, P12838, P08246, Q9C0K0, P41182, Q13547, Q92769, P12980, P24522

DDX5, MMP9, IL1R2, CEBPE, BCL2A1, TRAF1, BMI1, MPO, DEFA4, ELA2, BCL11B, BCL6, HDAC1, HDAC2, LYL1, GADD45A

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P17844	DDX5	Probable ATP-dependent RNA helicase DDX5	0.863
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14780	MMP9	Matrix metalloproteinase-9	0.94
P14780	MMP9	Matrix metalloproteinase-9	P14780	MMP9	Matrix metalloproteinase-9	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P27930	IL1R2	Interleukin-1 receptor type 2	0.926
P14780	MMP9	Matrix metalloproteinase-9	P27930	IL1R2	Interleukin-1 receptor type 2	0.851
P14780	MMP9	Matrix metalloproteinase-9	Q15744	CEBPE	CCAAT/enhancer-binding protein epsilon	0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16548	BCL2A1	Bcl-2-related protein A1	0.958
P14780	MMP9	Matrix metalloproteinase-9	Q16548	BCL2A1	Bcl-2-related protein A1	0.921
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13077	TRAF1	TNF receptor-associated factor 1	-0.796
P14780	MMP9	Matrix metalloproteinase-9	Q13077	TRAF1	TNF receptor-associated factor 1	-0.758
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P14780	MMP9	Matrix metalloproteinase-9	P35226	BMI1	Polycomb complex protein BMI-1	-0.89
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P14780	MMP9	Matrix metalloproteinase-9	P35226	BMI1	Polycomb complex protein BMI-1	-0.89
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P05164	MPO	Myeloperoxidase	0.719
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P12838	DEFA4	Neutrophil defensin 4	0.784
P14780	MMP9	Matrix metalloproteinase-9	P12838	DEFA4	Neutrophil defensin 4	0.858
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08246	ELA2	Neutrophil elastase	0.702
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.783
P14780	MMP9	Matrix metalloproteinase-9	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.752
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P41182	BCL6	B-cell lymphoma 6 protein	0.919
P14780	MMP9	Matrix metalloproteinase-9	P41182	BCL6	B-cell lymphoma 6 protein	0.812
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13547	HDAC1	Histone deacetylase 1	-0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q92769	HDAC2	Histone deacetylase 2	-0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P12980	LYL1	Protein lyl-1	0.784
P14780	MMP9	Matrix metalloproteinase-9	P12980	LYL1	Protein lyl-1	0.716
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.819
P14780	MMP9	Matrix metalloproteinase-9	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.765

Agomelatine

hsa05203

Viral carcinogenesis

8.69E-05

Q99941, P18848, P42338, P06746, P07948, P27348, P29083, Q13547, Q15283, P61586, P12814, P25963, P61978, P62807, Q93079

CREBL1, ATF4, PIK3CB, POLB, LYN, YWHAQ, GTF2E1, HDAC1, RASA2, RHOA, ACTN1, NFKBIA, HNRPK, HIST1H2BC, H2BC9

Agomelatine

hsa05206

MicroRNAs in cancer

1.34E-03

P30304, P09493, P21860, P01106, P42338, P61978, P46531, Q13547, P63279, P22105, P61586, P20827, P19174

CDC25A, TPM1, ERBB3, MYC, PIK3CB, HNRPK, NOTCH1, HDAC1, UBE2I, TNXB, RHOA, EFNA1, PLCG1

Agomelatine

hsa05212

Pancreatic cancer

3.94E-02

P42338, P84022, Q13485, O75293

PIK3CB, SMAD3, SMAD4, GADD45B

Agomelatine

hsa05214

Glioma

1.34E-02

P0DP23, P42338, P19174, O75293

CALM1, PIK3CB, PLCG1, GADD45B

Agomelatine

hsa05217

Basal cell carcinoma

3.50E-02

Q13635, P49841, Q9UJU2, P24522

PTCH1, GSK3B, LEF1, GADD45A

Agomelatine

hsa05218

Melanoma

2.31E-02

Q9NRA1, P42338, O75293

PDGFC, PIK3CB, GADD45B

Agomelatine

hsa05220

Chronic myeloid leukemia

1.15E-03

Q13547, P01106, Q13485, P25963, P84022, P42338, O75293

HDAC1, MYC, SMAD4, NFKBIA, SMAD3, PIK3CB, GADD45B

Agomelatine

hsa05231

Choline metabolism in cancer

2.92E-03

P42338, Q9NRA1, Q9Y259, P19174, P23743

PIK3CB, PDGFC, CHKB, PLCG1, DGKA

Agomelatine

hsa05235

PD-L1 expression and PD-1 checkpoint pathway in cancer

1.87E-04

P25963, P42338, O95267, P19174, P07766, P20963, P09693, P06239, P23458, P42224, O60603, Q04759, Q16539

NFKBIA, PIK3CB, RASGRP1, PLCG1, CD3E, CD247, CD3G, LCK, JAK1, STAT1, TLR2, PRKCQ, MAPK14

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.711
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.805
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.852
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.932
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.839
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
P40925	MDH1	Malate dehydrogenase, cytoplasmic	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.838
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60603	TLR2	Toll-like receptor 2	0.842
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883