PharmaCoNets

PharmaCoNets of Diphenoxylate (S_PCN: 157.32 )

Diphenoxylate regulated-network (S_DN: 21.17)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Diphenoxylate

hsa00030

Pentose phosphate pathway

1.69E-02

P60891, P37837

PRPS1, TALDO1

Diphenoxylate

hsa00052

Galactose metabolism

1.03E-02

P06280, O43451

GLA, MGAM

Diphenoxylate

hsa00071

Fatty acid degradation

3.65E-03

O75521, P00325, P11766, P33121

ECI2, ADH1B, ADH5, ACSL1

Diphenoxylate

hsa00190

Oxidative phosphorylation

1.36E-03

P13073, Q16718, O15239, P12074, P05496, O14521

COX4I1, NDUFA5, NDUFA1, COX6A1, ATP5G1, SDHD

Diphenoxylate

hsa00220

Arginine biosynthesis

1.21E-02

P15104

GLUL

Diphenoxylate

hsa00250

Alanine, aspartate and glutamate metabolism

2.42E-02

P15104

GLUL

Diphenoxylate

hsa00500

Starch and sucrose metabolism

9.77E-06

O43451, P46976, P35573, P06737

MGAM, GYG1, AGL, PYGL

Diphenoxylate

hsa00512

Mucin type O-glycan biosynthesis

3.78E-02

O95395, Q8N4A0

GCNT3, GALNT4

Diphenoxylate

hsa00520

Amino sugar and nucleotide sugar metabolism

2.11E-02

Q16222, Q9Y223, P06865

UAP1, GNE, HEXA

Diphenoxylate

hsa00524

Neomycin, kanamycin and gentamicin biosynthesis

2.03E-02

P35557

GCK

Diphenoxylate

hsa00590

Arachidonic acid metabolism

3.85E-02

P11712, P09960

CYP2C9, LTA4H

Diphenoxylate

hsa00591

Linoleic acid metabolism

4.07E-02

P11712

CYP2C9

Diphenoxylate

hsa00603

Glycosphingolipid biosynthesis - globo and isoglobo series

8.72E-03

P06865, O75752

HEXA, B3GALNT1

Diphenoxylate

hsa00604

Glycosphingolipid biosynthesis - ganglio series

2.46E-02

P06865, Q9H4F1

HEXA, ST6GALNAC4

Diphenoxylate

hsa00630

Glyoxylate and dicarboxylate metabolism

4.46E-03

P40925, P15104

MDH1, GLUL

Diphenoxylate

hsa00730

Thiamine metabolism

4.81E-06

Q9Y6K8, P05186, P24666

AK5, ALPL, ACP1

Diphenoxylate

hsa00740

Riboflavin metabolism

4.03E-02

P24666

ACP1

Diphenoxylate

hsa00770

Pantothenate and CoA biosynthesis

2.26E-04

O95498, O95497, Q9NRN7

VNN2, VNN1, AASDHPPT

Diphenoxylate

hsa00830

Retinol metabolism

2.20E-02

P00325, P11766, Q9BPW9, O75911

ADH1B, ADH5, DHRS9, DHRS3

Diphenoxylate

hsa00860

Porphyrin and chlorophyll metabolism

1.69E-02

P36551, P30043

CPOX, BLVRB

Diphenoxylate

hsa00910

Nitrogen metabolism

2.42E-02

P15104

GLUL

Diphenoxylate

hsa00920

Sulfur metabolism

3.18E-02

Q16762

TST

Diphenoxylate

hsa00970

Aminoacyl-tRNA biosynthesis

3.63E-07

O95363, P54136, P14868, Q15046

FARS2, RARS1, DARS, KARS

Diphenoxylate

hsa00980

Metabolism of xenobiotics by cytochrome P450

9.14E-03

P78417, P11712

GSTO1, CYP2C9

Diphenoxylate

hsa00982

Drug metabolism - cytochrome P450

9.14E-03

P11712, P78417

CYP2C9, GSTO1

Diphenoxylate

hsa00983

Drug metabolism - other enzymes

2.44E-02

P32320, P05164

CDA, MPO

Diphenoxylate

hsa01230

Biosynthesis of amino acids

1.90E-03

P60891, Q99707, P15104, P37837

PRPS1, MTR, GLUL, TALDO1

Diphenoxylate

hsa01240

Biosynthesis of cofactors

2.52E-02

Q9BQB6, P14550

VKORC1, AKR1A1

Diphenoxylate

hsa01524

Platinum drug resistance

1.13E-02

P10415, Q13489, P78417, P23025, P43246

BCL2, BIRC3, GSTO1, XPA, MSH2

Diphenoxylate

hsa02010

ABC transporters

1.98E-03

P45844, P08183, Q8IZY2

ABCG1, ABCB1, ABCA7

Diphenoxylate

hsa03008

Ribosome biogenesis in eukaryotes

1.31E-04

Q9NYH9, O14980, O60832, P78345, Q9BVP2, O15381, Q9GZY0

UTP6, XPO1, DKC1, RPP38, GNL3, NVL, NXF2; NXF2B

Diphenoxylate

hsa03010

Ribosome

6.10E-04

P62753, P39019, P42677, P62917, Q9H0U6, Q07020, P61513, Q02878, P63173, P27635, P05386, P23396

RPS6, RPS19, RPS27, RPL8, MRPL18, RPL18, RPL37A, RPL6, RPL38, RPL10, RPLP1, RPS3

Diphenoxylate

hsa03013

RNA transport

6.49E-10

O14980, P52298, Q09161, O14893, P61326, Q15287, Q9UBU9, Q7Z3B4, P35658, P63279, Q14152, P55884, O15371, O75822, P78345, P20042, Q14240, P23588, Q9Y6A5, P51114

XPO1, NCBP2, NCBP1, GEMIN2, MAGOH, RNPS1, NXF1, NUP54, NUP214, UBE2I, EIF3A, EIF3B, EIF3D, EIF3J, RPP38, EIF2S2, EIF4A2, EIF4B, TACC3, FXR1

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
Q92769	HDAC2	Histone deacetylase 2	O14980	XPO1	Exportin-1	0.75
P21462	FPR1	fMet-Leu-Phe receptor	O14980	XPO1	Exportin-1	-0.742
Q92769	HDAC2	Histone deacetylase 2	P52298	NCBP2	Nuclear cap-binding protein subunit 2	0.766
P21462	FPR1	fMet-Leu-Phe receptor	P52298	NCBP2	Nuclear cap-binding protein subunit 2	-0.874
P51684	CCR6	C-C chemokine receptor type 6	P52298	NCBP2	Nuclear cap-binding protein subunit 2	0.924
P21462	FPR1	fMet-Leu-Phe receptor	Q09161	NCBP1	Nuclear cap-binding protein subunit 1	-0.78
Q92769	HDAC2	Histone deacetylase 2	O14893	GEMIN2	Gem-associated protein 2	0.734
P21462	FPR1	fMet-Leu-Phe receptor	O14893	GEMIN2	Gem-associated protein 2	-0.87
P51684	CCR6	C-C chemokine receptor type 6	O14893	GEMIN2	Gem-associated protein 2	0.771
Q92769	HDAC2	Histone deacetylase 2	P61326	MAGOH	Protein mago nashi homolog	0.812
P21462	FPR1	fMet-Leu-Phe receptor	P61326	MAGOH	Protein mago nashi homolog	-0.835
P51684	CCR6	C-C chemokine receptor type 6	P61326	MAGOH	Protein mago nashi homolog	0.704
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q15287	RNPS1	RNA-binding protein with serine-rich domain 1	0.756
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q9UBU9	NXF1	Nuclear RNA export factor 1	0.723
Q92769	HDAC2	Histone deacetylase 2	Q7Z3B4	NUP54	Nucleoporin p54	0.775
P21462	FPR1	fMet-Leu-Phe receptor	Q7Z3B4	NUP54	Nucleoporin p54	-0.903
P51684	CCR6	C-C chemokine receptor type 6	Q7Z3B4	NUP54	Nucleoporin p54	0.811
Q92769	HDAC2	Histone deacetylase 2	P35658	NUP214	Nuclear pore complex protein Nup214	-0.729
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P35658	NUP214	Nuclear pore complex protein Nup214	-0.725
P21462	FPR1	fMet-Leu-Phe receptor	P35658	NUP214	Nuclear pore complex protein Nup214	0.971
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P63279	UBE2I	SUMO-conjugating enzyme UBC9	0.736
Q92769	HDAC2	Histone deacetylase 2	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	0.719
P21462	FPR1	fMet-Leu-Phe receptor	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	-0.89
P51684	CCR6	C-C chemokine receptor type 6	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	0.701
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P55884	EIF3B	Eukaryotic translation initiation factor 3 subunit B	-0.731
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	O15371	EIF3D	Eukaryotic translation initiation factor 3 subunit D	0.77
P21462	FPR1	fMet-Leu-Phe receptor	O75822	EIF3J	Eukaryotic translation initiation factor 3 subunit J	-0.953
P51684	CCR6	C-C chemokine receptor type 6	O75822	EIF3J	Eukaryotic translation initiation factor 3 subunit J	0.711
P51684	CCR6	C-C chemokine receptor type 6	P78345	RPP38	Ribonuclease P protein subunit p38	0.861
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P20042	EIF2S2	Eukaryotic translation initiation factor 2 subunit 2	0.733
Q92769	HDAC2	Histone deacetylase 2	Q14240	EIF4A2	Eukaryotic initiation factor 4A-II	0.79
P21462	FPR1	fMet-Leu-Phe receptor	Q14240	EIF4A2	Eukaryotic initiation factor 4A-II	-0.721
Q92769	HDAC2	Histone deacetylase 2	P23588	EIF4B	Eukaryotic translation initiation factor 4B	0.767
Q92769	HDAC2	Histone deacetylase 2	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	-0.758
P21462	FPR1	fMet-Leu-Phe receptor	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	0.904
P51684	CCR6	C-C chemokine receptor type 6	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	-0.732
P21462	FPR1	fMet-Leu-Phe receptor	P51114	FXR1	Fragile X mental retardation syndrome-related protein 1	-0.713

Diphenoxylate

hsa03020

RNA polymerase

9.86E-07

Q9GZM3, P52435

POLR2J2, POLR2J

Diphenoxylate

hsa03022

Basal transcription factors

3.32E-02

O00268, Q15544

TAF4, TAF11

Diphenoxylate

hsa03040

Spliceosome

5.30E-09

Q14562, O43143, O60508, Q99633, P08579, Q15427, P26368, P38159, P61978, Q13595, Q07955, Q01130, P84103, Q13243, Q9UMS4, P11142, Q9Y2W2, O43447, O75643

DHX8, DHX15, CDC40, PRPF18, SNRPB2, SF3B4, U2AF2, RBMX, HNRPK, TRA2A, SFRS1, SFRS2, SFRS3, SFRS5, PRPF19, 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
P46091	GPR1	Chemerin-like receptor 2	Q14562	DHX8	ATP-dependent RNA helicase DHX8	-0.819
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.76
P46091	GPR1	Chemerin-like receptor 2	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.816
P35610	SOAT1	Sterol O-acyltransferase 1	O60508	CDC40	Pre-mRNA-processing factor 17	0.76
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O60508	CDC40	Pre-mRNA-processing factor 17	-0.812
P46091	GPR1	Chemerin-like receptor 2	O60508	CDC40	Pre-mRNA-processing factor 17	-0.778
P46091	GPR1	Chemerin-like receptor 2	Q99633	PRPF18	Pre-mRNA-splicing factor 18	-0.711
P35610	SOAT1	Sterol O-acyltransferase 1	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.787
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	-0.822
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q15427	SF3B4	Splicing factor 3B subunit 4	0.71
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P26368	U2AF2	Splicing factor U2AF 65 kDa subunit	-0.751
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P38159	RBMX	RNA-binding motif protein, X chromosome	0.733
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P61978	HNRPK	Heterogeneous nuclear ribonucleoprotein K	0.784
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13595	TRA2A	Transformer-2 protein homolog alpha	-0.74
P46091	GPR1	Chemerin-like receptor 2	Q13595	TRA2A	Transformer-2 protein homolog alpha	-0.753
P35610	SOAT1	Sterol O-acyltransferase 1	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.712
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	-0.749
P35610	SOAT1	Sterol O-acyltransferase 1	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.822
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.798
P46091	GPR1	Chemerin-like receptor 2	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.746
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84103	SFRS3	Serine/arginine-rich splicing factor 3	-0.773
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	-0.822
P46091	GPR1	Chemerin-like receptor 2	Q9UMS4	PRPF19	Pre-mRNA-processing factor 19	0.703
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.766
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P11142	HSPA8	Heat shock cognate 71 kDa protein	-0.802
P35610	SOAT1	Sterol O-acyltransferase 1	Q9Y2W2	WBP11	WW domain-binding protein 11	0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q9Y2W2	WBP11	WW domain-binding protein 11	-0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	-0.766
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75643	ASCC3L1	U5 small nuclear ribonucleoprotein 200 kDa helicase	-0.745

Diphenoxylate

hsa03060

Protein export

1.13E-03

P37108, Q15005

SRP14, SPCS2

Diphenoxylate

hsa03410

Base excision repair

2.52E-02

P49005, P29372

POLD2, MPG

Diphenoxylate

hsa03450

Non-homologous end-joining

4.21E-02

P13010

XRCC5

Diphenoxylate

hsa04012

ErbB signaling pathway

3.74E-02

P21860, Q13557, O14944

ERBB3, CAMK2D, EREG

Diphenoxylate

hsa04014

Ras signaling pathway

1.98E-03

P42338, P20827, P49767, Q13009, Q7LDG7, P63218, P50151, P19174

PIK3CB, EFNA1, VEGFC, TIAM1, RASGRP2, GNG5, GNG10, PLCG1

Diphenoxylate

hsa04015

Rap1 signaling pathway

1.45E-04

P20827, P49767, P63261, Q96FS4, P11215, P25116, Q8TEU7, Q13009, Q7LDG7, P42338, P0DP23, P08514, P17252, P19174

EFNA1, VEGFC, ACTG1, SIPA1, ITGAM, F2R, RAPGEF6, TIAM1, RASGRP2, PIK3CB, CALM1, ITGA2B, PRKCA, PLCG1

Diphenoxylate

hsa04020

Calcium signaling pathway

1.73E-07

Q96DU7, Q08828, P45880, Q16566, Q13557, P17252, P21860, O15399, P25116, P0DP23, P05141, P51828, P23634, P49767

ITPKC, ADCY1, VDAC2, CAMK4, CAMK2D, PRKCA, ERBB3, GRIN2D, F2R, CALM1, SLC25A5, ADCY7, ATP2B4, VEGFC

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
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	Q96DU7	ITPKC	Inositol-trisphosphate 3-kinase C	-0.839
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q96DU7	ITPKC	Inositol-trisphosphate 3-kinase C	-0.802
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	Q08828	ADCY1	Adenylate cyclase type 1	0.741
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P45880	VDAC2	Voltage-dependent anion-selective channel protein 2	0.708
P46091	GPR1	Chemerin-like receptor 2	Q16566	CAMK4	Calcium/calmodulin-dependent protein kinase type IV	0.865
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.784
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.707
P46091	GPR1	Chemerin-like receptor 2	P17252	PRKCA	Protein kinase C alpha type	0.741
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P21860	ERBB3	Receptor tyrosine-protein kinase erbB-3	-0.785
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P21860	ERBB3	Receptor tyrosine-protein kinase erbB-3	-0.772
P46091	GPR1	Chemerin-like receptor 2	O15399	GRIN2D	Glutamate receptor ionotropic, NMDA 2D	0.744
P46091	GPR1	Chemerin-like receptor 2	P25116	F2R	Proteinase-activated receptor 1	0.76
P46091	GPR1	Chemerin-like receptor 2	P0DP23	CALM1	Calmodulin-1	-0.846
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05141	SLC25A5	ADP/ATP translocase 2	0.75
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P51828	ADCY7	Adenylate cyclase type 7	0.704
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.73
P46091	GPR1	Chemerin-like receptor 2	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	-0.766
P46091	GPR1	Chemerin-like receptor 2	P49767	VEGFC	Vascular endothelial growth factor C	0.718

Diphenoxylate

hsa04022

cGMP-PKG signaling pathway

4.72E-02

Q99941, P23634, P51828, P45880

CREBL1, ATP2B4, ADCY7, VDAC2

Diphenoxylate

hsa04024

cAMP signaling pathway

2.84E-02

P0DP23, P23634, Q16566, O15399, P25116

CALM1, ATP2B4, CAMK4, GRIN2D, F2R

Diphenoxylate

hsa04061

Viral protein interaction with cytokine and cytokine receptor

3.57E-03

Q8NHW4, P09341, P19875, P25024, P25025, P61073, Q13651, P14784

CCL4L2, CXCL1, CXCL2, CXCR1, CXCR2, CXCR4, IL10RA, IL2RB

Diphenoxylate

hsa04062

Chemokine signaling pathway

9.51E-06

P25024, P25025, P09341, P19875, P47992, Q9UBD3, P09769, P07948, P42338, P19174, P63218, P50151, P43250, P49407, Q08881, Q7LDG7, Q13009, P49841, Q8WYR1

CXCR1, CXCR2, CXCL1, CXCL2, XCL1, XCL2, FGR, LYN, PIK3CB, PLCG1, GNG5, GNG10, GRK6, ARRB1, ITK, RASGRP2, TIAM1, GSK3B, 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
P25024	CXCR1	C-X-C chemokine receptor type 1	P25024	CXCR1	C-X-C chemokine receptor type 1	1
Q13547	HDAC1	Histone deacetylase 1	P25025	CXCR2	C-X-C chemokine receptor type 2	-0.719
P25024	CXCR1	C-X-C chemokine receptor type 1	P25025	CXCR2	C-X-C chemokine receptor type 2	0.929
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
P25024	CXCR1	C-X-C chemokine receptor type 1	P47992	XCL1	Lymphotactin	-0.706
P25024	CXCR1	C-X-C chemokine receptor type 1	Q9UBD3	XCL2	Cytokine SCM-1 beta	-0.706
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P09769	FGR	Tyrosine-protein kinase Fgr	0.796
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P07948	LYN	Tyrosine-protein kinase Lyn	0.971
P25024	CXCR1	C-X-C chemokine receptor type 1	P07948	LYN	Tyrosine-protein kinase Lyn	0.707
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
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
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
P25024	CXCR1	C-X-C chemokine receptor type 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.727
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
P25024	CXCR1	C-X-C chemokine receptor type 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43250	GRK6	G protein-coupled receptor kinase 6	0.818
P25024	CXCR1	C-X-C chemokine receptor type 1	P49407	ARRB1	Beta-arrestin-1	-0.721
P25024	CXCR1	C-X-C chemokine receptor type 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.736
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	0.706
P25024	CXCR1	C-X-C chemokine receptor type 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.823
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q8WYR1	PIK3R5	Phosphoinositide 3-kinase regulatory subunit 5	0.752

Diphenoxylate

hsa04064

NF-kappa B signaling pathway

3.31E-07

P10415, Q13489, P51617, O00463, Q13546, P14778, P01584, P01375, P19174, Q04759, Q9UDY8, Q13077, P67870, Q16548, P06239, Q8WV28, P63279, P24522, Q8NHW4, P09341, P19875, Q06643, Q9UNE0, Q9NQC7

BCL2, BIRC3, IRAK1, TRAF5, RIPK1, IL1R1, IL1B, TNF, PLCG1, PRKCQ, MALT1, TRAF1, CSNK2B, BCL2A1, LCK, BLNK, UBE2I, GADD45A, CCL4L2, CXCL1, CXCL2, LTB, EDAR, CYLD

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
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P08235	NR3C2	Mineralocorticoid receptor	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.868
P51684	CCR6	C-C chemokine receptor type 6	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	0.722
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O00463	TRAF5	TNF receptor-associated factor 5	-0.932
P08235	NR3C2	Mineralocorticoid receptor	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.749
P51684	CCR6	C-C chemokine receptor type 6	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.868
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	P01584	IL1B	Interleukin-1 beta	0.807
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P01584	IL1B	Interleukin-1 beta	0.762
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
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
P08235	NR3C2	Mineralocorticoid receptor	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.708
P51684	CCR6	C-C chemokine receptor type 6	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.869
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13077	TRAF1	TNF receptor-associated factor 1	-0.796
P51684	CCR6	C-C chemokine receptor type 6	Q13077	TRAF1	TNF receptor-associated factor 1	0.768
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P67870	CSNK2B	Casein kinase II subunit beta	0.709
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16548	BCL2A1	Bcl-2-related protein A1	0.958
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	Q8WV28	BLNK	B-cell linker protein	-0.704
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P63279	UBE2I	SUMO-conjugating enzyme UBC9	0.702
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.819
P51684	CCR6	C-C chemokine receptor type 6	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.712
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.727
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.727
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09341	CXCL1	Growth-regulated alpha protein	0.788
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
Q13547	HDAC1	Histone deacetylase 1	Q06643	LTB	Lymphotoxin-beta	0.74
P08235	NR3C2	Mineralocorticoid receptor	Q9UNE0	EDAR	Tumor necrosis factor receptor superfamily member EDAR	0.819
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.799
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.763

Diphenoxylate

hsa04070

Phosphatidylinositol signaling system

4.07E-02

P0DP23, Q14643, O14732, P17252

CALM1, ITPR1, IMPA2, PRKCA

Diphenoxylate

hsa04071

Sphingolipid signaling pathway

3.08E-05

P17252, Q9H228, P01375, Q13362, Q16537, Q9BX95, Q16539, P04637, P10415, Q9UQC2

PRKCA, EDG8, TNF, PPP2R5C, PPP2R5E, SGPP1, MAPK14, TP53, BCL2, GAB2

Diphenoxylate

hsa04072

Phospholipase D signaling pathway

4.48E-02

P42338, P43657, P25024, P25025, P19174

PIK3CB, P2RY5, CXCR1, CXCR2, PLCG1

Diphenoxylate

hsa04114

Oocyte meiosis

2.05E-02

Q9Y6D9, P51812, Q02750, P16298, Q17RY0

MAD1L1, RPS6KA3, MAP2K1, PPP3CB, CPEB4

Diphenoxylate

hsa04120

Ubiquitin mediated proteolysis

3.44E-02

Q14145, Q13042, P62837, Q15751

KEAP1, CDC16, UBE2D2, HERC1

Diphenoxylate

hsa04122

Sulfur relay system

3.18E-02

Q16762

TST

Diphenoxylate

hsa04136

Autophagy - other

5.92E-03

O94817, Q9H1Y0

ATG12, ATG5

Diphenoxylate

hsa04141

Protein processing in endoplasmic reticulum

3.64E-02

Q99941, O75460, P11142, Q9H3Z4, P07900

CREBL1, ERN1, HSPA8, DNAJC5, HSP90AA1

Diphenoxylate

hsa04142

Lysosome

2.64E-02

Q99437, P25774

ATP6V0B, CTSS

Diphenoxylate

hsa04145

Phagosome

5.85E-03

P63261, Q15080, Q13509, P68371, Q99437, P27824, P25774

ACTG1, NCF4, TUBB3, TUBB2C, ATP6V0B, CANX, CTSS

Diphenoxylate

hsa04151

PI3K-Akt signaling pathway

1.89E-03

P42338, P43657, P20827, P49767, P08238, Q8WYR1, P63218, P50151, O15335, Q13751, P14784, P30281

PIK3CB, P2RY5, EFNA1, VEGFC, HSP90AB1, PIK3R5, GNG5, GNG10, CHAD, LAMB3, IL2RB, CCND3

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
P35610	SOAT1	Sterol O-acyltransferase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.813
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P35610	SOAT1	Sterol O-acyltransferase 1	P43657	P2RY5	Lysophosphatidic acid receptor 6	0.784
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P35610	SOAT1	Sterol O-acyltransferase 1	P20827	EFNA1	Ephrin-A1	-0.763
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P20827	EFNA1	Ephrin-A1	0.715
P35610	SOAT1	Sterol O-acyltransferase 1	P49767	VEGFC	Vascular endothelial growth factor C	-0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q8WYR1	PIK3R5	Phosphoinositide 3-kinase regulatory subunit 5	0.752
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P35610	SOAT1	Sterol O-acyltransferase 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.838
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P35610	SOAT1	Sterol O-acyltransferase 1	O15335	CHAD	Chondroadherin	-0.792
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O15335	CHAD	Chondroadherin	0.795
P35610	SOAT1	Sterol O-acyltransferase 1	Q13751	LAMB3	Laminin subunit beta-3	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13751	LAMB3	Laminin subunit beta-3	0.844
P35610	SOAT1	Sterol O-acyltransferase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.779
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743

Diphenoxylate

hsa04210

Apoptosis

3.58E-02

O76075, P01375, Q9NR28, Q16548

DFFB, TNF, DIABLO, BCL2A1

Diphenoxylate

hsa04211

Longevity regulating pathway

1.18E-02

Q12778, Q9UEF7, Q96KQ7

FOXO1, KL, EHMT2

Diphenoxylate

hsa04213

Longevity regulating pathway - multiple species

4.41E-03

P42338, Q9Y4H2, P11142, Q13547

PIK3CB, IRS2, HSPA8, HDAC1

Diphenoxylate

hsa04217

Necroptosis

1.85E-03

P01375, P01568, P48023, Q13489, Q13546, Q14765, Q99878

TNF, IFNA21, FASLG, BIRC3, RIPK1, STAT4, H2AC14

Diphenoxylate

hsa04260

Cardiac muscle contraction

4.49E-02

P67936, P13073, P12074

TPM4, COX4I1, COX6A1

Diphenoxylate

hsa04261

Adrenergic signaling in cardiomyocytes

4.32E-03

P51828, Q99941, Q16537, P0DP23, Q13557, P17252, P10415, P20020, P23634

ADCY7, CREBL1, PPP2R5E, CALM1, CAMK2D, PRKCA, BCL2, ATP2B1, ATP2B4

Diphenoxylate

hsa04330

Notch signaling pathway

4.34E-02

Q92542, P46531

NCSTN, NOTCH1

Diphenoxylate

hsa04340

Hedgehog signaling pathway

4.15E-03

P49841, P22694, Q13635, P10415

GSK3B, PRKACB, PTCH1, BCL2

Diphenoxylate

hsa04350

TGF-beta signaling pathway

4.88E-02

P37173

TGFBR2

Diphenoxylate

hsa04360

Axon guidance

4.04E-02

P16333, P20827, O95631, P42338, P07332, P19174

NCK1, EFNA1, NTN1, PIK3CB, FES, PLCG1

Diphenoxylate

hsa04370

VEGF signaling pathway

1.29E-02

P16298, Q05397, Q02750

PPP3CB, PTK2, MAP2K1

Diphenoxylate

hsa04371

Apelin signaling pathway

1.00E-02

P63218, P50151, Q8WYR1, Q14814, Q14344, Q13485, P84022

GNG5, GNG10, PIK3R5, MEF2D, GNA13, SMAD4, SMAD3

Diphenoxylate

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

Diphenoxylate

hsa04390

Hippo signaling pathway

1.47E-02

P63261, Q13485, Q9UJU2, O43623, Q13489

ACTG1, SMAD4, LEF1, SNAI2, BIRC3

Diphenoxylate

hsa04510

Focal adhesion

3.21E-02

Q15942, P17252, Q13489, P10415, P49767, P63261

ZYX, PRKCA, BIRC3, BCL2, VEGFC, ACTG1

Diphenoxylate

hsa04512

ECM-receptor interaction

3.73E-02

P07359, P08514

GP1BA, ITGA2B

Diphenoxylate

hsa04514

Cell adhesion molecules

8.19E-03

P16109, P56750, O00501

SELP, CLDN17, CLDN5

Diphenoxylate

hsa04520

Adherens junction

3.36E-02

Q13485, Q9UJU2, O43623, P63261

SMAD4, LEF1, SNAI2, ACTG1

Diphenoxylate

hsa04530

Tight junction

2.47E-05

Q8TEU7, P16989, P56750, O00501, Q14247

RAPGEF6, CSDA, CLDN17, CLDN5, CTTN

Diphenoxylate

hsa04540

Gap junction

4.76E-02

P17252, Q13509, P68371

PRKCA, TUBB3, TUBB2C

Diphenoxylate

hsa04610

Complement and coagulation cascades

1.45E-05

P25116, P09871, P0C0L4

F2R, C1S, C4A

Diphenoxylate

hsa04611

Platelet activation

5.18E-05

P25116, P08514, Q15746, Q8WYR1, P07359

F2R, ITGA2B, MYLK, PIK3R5, GP1BA

Diphenoxylate

hsa04612

Antigen processing and presentation

5.92E-05

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

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

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
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P25025	CXCR2	C-X-C chemokine receptor type 2	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.7
P14780	MMP9	Matrix metalloproteinase-9	P48382	RFX5	DNA-binding protein RFX5	-0.874
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P48382	RFX5	DNA-binding protein RFX5	-0.738
P25025	CXCR2	C-X-C chemokine receptor type 2	P48382	RFX5	DNA-binding protein RFX5	-0.743
P14780	MMP9	Matrix metalloproteinase-9	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.867
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.714
P14780	MMP9	Matrix metalloproteinase-9	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.867
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.714
P14780	MMP9	Matrix metalloproteinase-9	Q13241	KLRD1	Natural killer cells antigen CD94	-0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.856
P25025	CXCR2	C-X-C chemokine receptor type 2	Q13241	KLRD1	Natural killer cells antigen CD94	-0.715
P14780	MMP9	Matrix metalloproteinase-9	O43908	KLRC4	NKG2-F type II integral membrane protein	-0.792
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O43908	KLRC4	NKG2-F type II integral membrane protein	-0.741
P25025	CXCR2	C-X-C chemokine receptor type 2	O43908	KLRC4	NKG2-F type II integral membrane protein	-0.721
P14780	MMP9	Matrix metalloproteinase-9	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.742
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.816
P25025	CXCR2	C-X-C chemokine receptor type 2	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.722
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774

Diphenoxylate

hsa04613

Neutrophil extracellular trap formation

7.68E-09

P17252, P16109, P11215, O60603, P05164, P08246, Q9UM07, Q13547, Q92769, P04908, P0C0S5, Q6FI13, Q93077, P58876, P62807, P33778, Q16778, O60814, P68431, P14598, Q15080, P20160, P08311, O75015, P21730, P08514, P21462, P07359, O43315, Q16539

PRKCA, SELP, ITGAM, TLR2, MPO, ELA2, PADI4, HDAC1, HDAC2, H2AC4; H2AC8, H2AFZ, H2AC18; H2AC19, HIST1H2AC, H2BC5, HIST1H2BC, H2BC3, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12, 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
P51684	CCR6	C-C chemokine receptor type 6	P17252	PRKCA	Protein kinase C alpha type	0.738
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P16109	SELP	P-selectin	0.819
O15245	SLC22A1	Solute carrier family 22 member 1	P11215	ITGAM	Integrin alpha-M	0.706
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P51684	CCR6	C-C chemokine receptor type 6	O60603	TLR2	Toll-like receptor 2	-0.767
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P05164	MPO	Myeloperoxidase	0.719
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08246	ELA2	Neutrophil elastase	0.702
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
P51684	CCR6	C-C chemokine receptor type 6	P08246	ELA2	Neutrophil elastase	-0.706
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.825
O15245	SLC22A1	Solute carrier family 22 member 1	Q13547	HDAC1	Histone deacetylase 1	-0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13547	HDAC1	Histone deacetylase 1	-0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13547	HDAC1	Histone deacetylase 1	-0.742
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q92769	HDAC2	Histone deacetylase 2	-0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q92769	HDAC2	Histone deacetylase 2	-0.746
P51684	CCR6	C-C chemokine receptor type 6	Q92769	HDAC2	Histone deacetylase 2	0.702
P31645	SLC6A4	Sodium-dependent serotonin transporter	P04908	H2AC4; H2AC8	Histone H2A type 1-B/E	0.734
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
P51684	CCR6	C-C chemokine receptor type 6	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	-0.86
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q93077	HIST1H2AC	Histone H2A type 1-C	0.737
P11712	CYP2C9	Cytochrome P450 2C9	Q93077	HIST1H2AC	Histone H2A type 1-C	0.754
O15245	SLC22A1	Solute carrier family 22 member 1	P58876	H2BC5	Histone H2B type 1-D	0.947
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
P51684	CCR6	C-C chemokine receptor type 6	P33778	H2BC3	Histone H2B type 1-B	0.704
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
O15245	SLC22A1	Solute carrier family 22 member 1	Q16778	HIST2H2BE	Histone H2B type 2-E	0.793
O15245	SLC22A1	Solute carrier family 22 member 1	O60814	H2BC12	Histone H2B type 1-K	0.72
P11712	CYP2C9	Cytochrome P450 2C9	O60814	H2BC12	Histone H2B type 1-K	0.728
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	O60814	H2BC12	Histone H2B type 1-K	0.783
P31645	SLC6A4	Sodium-dependent serotonin transporter	P68431	H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12	Histone H3.1	0.913
P11712	CYP2C9	Cytochrome P450 2C9	P68431	H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12	Histone H3.1	0.845
P51684	CCR6	C-C chemokine receptor type 6	P14598	NCF1	Neutrophil cytosol factor 1	-0.713
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q15080	NCF4	Neutrophil cytosol factor 4	0.764
P51684	CCR6	C-C chemokine receptor type 6	Q15080	NCF4	Neutrophil cytosol factor 4	-0.803
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08311	CTSG	Cathepsin G	0.709
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	1
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21462	FPR1	fMet-Leu-Phe receptor	0.842
P51684	CCR6	C-C chemokine receptor type 6	P21462	FPR1	fMet-Leu-Phe receptor	-0.7
P18054	ALOX12	Polyunsaturated fatty acid lipoxygenase ALOX12	P07359	GP1BA	Platelet glycoprotein Ib alpha chain	0.876
P31645	SLC6A4	Sodium-dependent serotonin transporter	O43315	AQP9	Aquaporin-9	-0.764
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O43315	AQP9	Aquaporin-9	0.934
P14780	MMP9	Matrix metalloproteinase-9	O43315	AQP9	Aquaporin-9	0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O43315	AQP9	Aquaporin-9	0.915
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16539	MAPK14	Mitogen-activated protein kinase 14	-0.744
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833

Diphenoxylate

hsa04614

Renin-angiotensin system

7.48E-03

P50052, P15144, P08311, O75787

AGTR2, ANPEP, CTSG, ATP6AP2

Diphenoxylate

hsa04620

Toll-like receptor signaling pathway

4.16E-02

Q13546, P01568

RIPK1, IFNA21

Diphenoxylate

hsa04621

NOD-like receptor signaling pathway

6.46E-03

Q16539, Q14643, P01568, Q13489, P10599, Q9H1Y0, P43490, O00463, P10415, Q13546, Q05823, P01375, P09341, P12838

MAPK14, ITPR1, IFNA21, BIRC3, TXN, ATG5, PBEF1, TRAF5, BCL2, RIPK1, RNASEL, TNF, CXCL1, DEFA4

Diphenoxylate

hsa04622

RIG-I-like receptor signaling pathway

2.39E-02

P01568, Q13546

IFNA21, RIPK1

Diphenoxylate

hsa04623

Cytosolic DNA-sensing pathway

8.25E-05

P01584, P01568, Q13546, Q8NHW4

IL1B, IFNA21, RIPK1, CCL4L2

Diphenoxylate

hsa04625

C-type lectin receptor signaling pathway

1.11E-03

Q9ULY5, P01584, Q9NQC7, P20749, Q14643, P01375, Q13191, P0DP24, Q16539

CLEC4E, IL1B, CYLD, BCL3, ITPR1, TNF, CBLB, CALM2, MAPK14

Diphenoxylate

hsa04640

Hematopoietic cell lineage

2.12E-04

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

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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13612	ITGA4	Integrin alpha-4	-0.771
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14778	IL1R1	Interleukin-1 receptor type 1	0.762
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P27930	IL1R2	Interleukin-1 receptor type 2	0.926
Q13547	HDAC1	Histone deacetylase 1	P27930	IL1R2	Interleukin-1 receptor type 2	-0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
Q13547	HDAC1	Histone deacetylase 1	P11215	ITGAM	Integrin alpha-M	-0.751
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P15144	ANPEP	Aminopeptidase N	0.851
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P15144	ANPEP	Aminopeptidase N	0.879
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P11836	MS4A1	B-lymphocyte antigen CD20	-0.71
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P11836	MS4A1	B-lymphocyte antigen CD20	-0.705
Q13547	HDAC1	Histone deacetylase 1	P25063	CD24	Signal transducer CD24	-0.706
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.781
Q13547	HDAC1	Histone deacetylase 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.816
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.816
Q13547	HDAC1	Histone deacetylase 1	P09564	CD7	T-cell antigen CD7	0.738
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807

Diphenoxylate

hsa04650

Natural killer cell mediated cytotoxicity

1.27E-08

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

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	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P25024	CXCR1	C-X-C chemokine receptor type 1	P01375	TNF	Tumor necrosis factor	0.718
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P78314	SH3BP2	SH3 domain-binding protein 2	0.761
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P78314	SH3BP2	SH3 domain-binding protein 2	0.809
P25025	CXCR2	C-X-C chemokine receptor type 2	P78314	SH3BP2	SH3 domain-binding protein 2	0.748
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
P25024	CXCR1	C-X-C chemokine receptor type 1	P06239	LCK	Tyrosine-protein kinase Lck	-0.779
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.823
Q13547	HDAC1	Histone deacetylase 1	O60880	SH2D1A	SH2 domain-containing protein 1A	0.786
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.81
P25025	CXCR2	C-X-C chemokine receptor type 2	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.751
P25024	CXCR1	C-X-C chemokine receptor type 1	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.788
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
P25025	CXCR2	C-X-C chemokine receptor type 2	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.722
P25024	CXCR1	C-X-C chemokine receptor type 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.771
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13241	KLRD1	Natural killer cells antigen CD94	-0.82
Q13547	HDAC1	Histone deacetylase 1	Q13241	KLRD1	Natural killer cells antigen CD94	0.807
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.856
P25025	CXCR2	C-X-C chemokine receptor type 2	Q13241	KLRD1	Natural killer cells antigen CD94	-0.715
P25024	CXCR1	C-X-C chemokine receptor type 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.701
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.91
Q13547	HDAC1	Histone deacetylase 1	P26718	KLRK1	NKG2-D type II integral membrane protein	0.772
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.879
P25025	CXCR2	C-X-C chemokine receptor type 2	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.842
P25024	CXCR1	C-X-C chemokine receptor type 1	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.81
Q13547	HDAC1	Histone deacetylase 1	O14931	NCR3	Natural cytotoxicity triggering receptor 3	0.735
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.92
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
P25025	CXCR2	C-X-C chemokine receptor type 2	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.913
P25024	CXCR1	C-X-C chemokine receptor type 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.896
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.846
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.714
P25024	CXCR1	C-X-C chemokine receptor type 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.721
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.846
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.714
P25024	CXCR1	C-X-C chemokine receptor type 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.721

Diphenoxylate

hsa04657

IL-17 signaling pathway

2.42E-06

P25963, O00463, Q16539, P49841, P09341, P14780, P04141, P80188, P01375, P06702, P01584

NFKBIA, TRAF5, MAPK14, GSK3B, CXCL1, MMP9, CSF2, LCN2, TNF, S100A9, IL1B

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
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.865
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O00463	TRAF5	TNF receptor-associated factor 5	-0.932
P14780	MMP9	Matrix metalloproteinase-9	O00463	TRAF5	TNF receptor-associated factor 5	-0.917
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O00463	TRAF5	TNF receptor-associated factor 5	-0.875
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.781
P08183	ABCB1	ATP-dependent translocase ABCB1	P49841	GSK3B	Glycogen synthase kinase-3 beta	-0.725
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09341	CXCL1	Growth-regulated alpha protein	0.781
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14780	MMP9	Matrix metalloproteinase-9	0.94
P14780	MMP9	Matrix metalloproteinase-9	P14780	MMP9	Matrix metalloproteinase-9	1
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14780	MMP9	Matrix metalloproteinase-9	0.942
P08183	ABCB1	ATP-dependent translocase ABCB1	P14780	MMP9	Matrix metalloproteinase-9	-0.775
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P04141	CSF2	Granulocyte-macrophage colony-stimulating factor	-0.749
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.798
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.715
P14780	MMP9	Matrix metalloproteinase-9	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.888
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.721
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P01375	TNF	Tumor necrosis factor	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P08183	ABCB1	ATP-dependent translocase ABCB1	P01375	TNF	Tumor necrosis factor	-0.769
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P06702	S100A9	Protein S100-A9	0.859
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807

Diphenoxylate

hsa04658

Th1 and Th2 cell differentiation

3.74E-08

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

PRKCQ, CD3E, CD247, CD3G, MAPK14, PLCG1, LCK, 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
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q04759	PRKCQ	Protein kinase C theta type	-0.762
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
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
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.768
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UL17	TBX21	T-box transcription factor TBX21	-0.861
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
Q13547	HDAC1	Histone deacetylase 1	Q13761	RUNX3	Runt-related transcription factor 3	0.884

Diphenoxylate

hsa04659

Th17 cell differentiation

8.54E-07

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

PRKCQ, MAPK14, PLCG1, LCK, 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
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q04759	PRKCQ	Protein kinase C theta type	-0.762
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
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
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14778	IL1R1	Interleukin-1 receptor type 1	0.762
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UL17	TBX21	T-box transcription factor TBX21	-0.861
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.763
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
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
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757

Diphenoxylate

hsa04660

T cell receptor signaling pathway

5.83E-10

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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P25024	CXCR1	C-X-C chemokine receptor type 1	P01375	TNF	Tumor necrosis factor	0.718
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q04759	PRKCQ	Protein kinase C theta type	-0.762
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.806
P25025	CXCR2	C-X-C chemokine receptor type 2	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.716
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.812
P25025	CXCR2	C-X-C chemokine receptor type 2	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.746
P25024	CXCR1	C-X-C chemokine receptor type 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.736
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
P25025	CXCR2	C-X-C chemokine receptor type 2	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.722
P25024	CXCR1	C-X-C chemokine receptor type 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.771
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P25025	CXCR2	C-X-C chemokine receptor type 2	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.77
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.816
P25025	CXCR2	C-X-C chemokine receptor type 2	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.722
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.816
P25025	CXCR2	C-X-C chemokine receptor type 2	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.719
P25024	CXCR1	C-X-C chemokine receptor type 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.734
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
P25024	CXCR1	C-X-C chemokine receptor type 1	P06239	LCK	Tyrosine-protein kinase Lck	-0.779
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
P25025	CXCR2	C-X-C chemokine receptor type 2	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.889
P25024	CXCR1	C-X-C chemokine receptor type 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.795
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.781
P25025	CXCR2	C-X-C chemokine receptor type 2	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.861
P25024	CXCR1	C-X-C chemokine receptor type 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.823

Diphenoxylate

hsa04662

B cell receptor signaling pathway

9.03E-05

P42338, P60033, P07948, P21854, Q8N149

PIK3CB, CD81, LYN, CD72, LILRA2

Diphenoxylate

hsa04664

Fc epsilon RI signaling pathway

1.29E-03

P42338, P07948, P19174, P09917

PIK3CB, LYN, PLCG1, ALOX5

Diphenoxylate

hsa04666

Fc gamma R-mediated phagocytosis

2.22E-02

P49006, P06396, P14598, P17252

MARCKSL1, GSN, NCF1, PRKCA

Diphenoxylate

hsa04668

TNF signaling pathway

4.74E-02

Q99941, P01584, O95429

CREBL1, IL1B, BAG4

Diphenoxylate

hsa04710

Circadian rhythm

1.67E-02

Q16526, Q9Y478

CRY1, PRKAB1

Diphenoxylate

hsa04714

Thermogenesis

2.22E-04

Q16539, Q08828, P62753, P33121, P13073, P12074, O15239, Q16718, O14521, P05496

MAPK14, ADCY1, RPS6, ACSL1, COX4I1, COX6A1, NDUFA1, NDUFA5, SDHD, ATP5G1

Diphenoxylate

hsa04720

Long-term potentiation

3.70E-04

P17252, Q16566, P0DP23, O15399, Q14643

PRKCA, CAMK4, CALM1, GRIN2D, ITPR1

Diphenoxylate

hsa04722

Neurotrophin signaling pathway

3.27E-02

P49841, O43524, P48023

GSK3B, FOXO3, FASLG

Diphenoxylate

hsa04724

Glutamatergic synapse

3.24E-02

P43003, P50151, P15104

SLC1A3, GNG10, GLUL

Diphenoxylate

hsa04728

Dopaminergic synapse

2.82E-02

P14416, P63218, P50151, P49841, Q16539, P49407

DRD2, GNG5, GNG10, GSK3B, MAPK14, ARRB1

Diphenoxylate

hsa04750

Inflammatory mediator regulation of TRP channels

4.09E-05

P14778, P01584, P51828, P22694, Q13557, Q16539, P19174, P42338, Q14643, P24723, Q04759, P0DP24

IL1R1, IL1B, ADCY7, PRKACB, CAMK2D, MAPK14, PLCG1, PIK3CB, ITPR1, PRKCH, PRKCQ, CALM2

Diphenoxylate

hsa04810

Regulation of actin cytoskeleton

2.58E-02

Q15746, P08514, P25116

MYLK, ITGA2B, F2R

Diphenoxylate

hsa04910

Insulin signaling pathway

2.35E-02

P22694, P06737, P49841

PRKACB, PYGL, GSK3B

Diphenoxylate

hsa04911

Insulin secretion

1.13E-03

Q08828, P51828, Q99941, P18848, Q13557

ADCY1, ADCY7, CREBL1, ATF4, CAMK2D

Diphenoxylate

hsa04912

GnRH signaling pathway

7.90E-05

P17252, Q08828, P51828, P18848, Q13557, Q16539, Q99759, Q9Y6R4, Q14643, P0DP24, P0DP23, P22694

PRKCA, ADCY1, ADCY7, ATF4, CAMK2D, MAPK14, MAP3K3, MAP3K4, ITPR1, CALM2, CALM1, PRKACB

Diphenoxylate

hsa04914

Progesterone-mediated oocyte maturation

2.66E-02

Q17RY0, Q9Y6D9, P51812, Q02750

CPEB4, MAD1L1, RPS6KA3, MAP2K1

Diphenoxylate

hsa04915

Estrogen signaling pathway

4.72E-02

Q99941, P51828, P07900, P11142

CREBL1, ADCY7, HSP90AA1, HSPA8

Diphenoxylate

hsa04916

Melanogenesis

3.55E-02

P0DP23, Q9UJU2, P17252

CALM1, LEF1, PRKCA

Diphenoxylate

hsa04919

Thyroid hormone signaling pathway

7.11E-03

P49841, P22694, O60244, Q9NVC6

GSK3B, PRKACB, MED14, MED17

Diphenoxylate

hsa04920

Adipocytokine signaling pathway

3.96E-04

P25963, P33121, Q9Y478, Q04759, Q96RR4, Q15831, P20333, Q9Y4H2, P01375

NFKBIA, ACSL1, PRKAB1, PRKCQ, CAMKK2, STK11, TNFRSF1B, IRS2, TNF

Diphenoxylate

hsa04921

Oxytocin signaling pathway

4.19E-02

P0DP23, P17252, Q16566, P63261

CALM1, PRKCA, CAMK4, ACTG1

Diphenoxylate

hsa04923

Regulation of lipolysis in adipocytes

2.24E-02

P07550, P42338, Q9Y4H2

ADRB2, PIK3CB, IRS2

Diphenoxylate

hsa04925

Aldosterone synthesis and secretion

5.60E-06

Q14643, Q99941, P51828, P0DP23, P17252, Q16566, Q13557, P20020, P23634

ITPR1, CREBL1, ADCY7, CALM1, PRKCA, CAMK4, CAMK2D, ATP2B1, ATP2B4

Diphenoxylate

hsa04931

Insulin resistance

1.94E-02

P01375, P49841, P06737

TNF, GSK3B, PYGL

Diphenoxylate

hsa04932

Non-alcoholic fatty liver disease

2.85E-06

P01375, P49841, O43521, P18848, P48023, O75460, P01584, P13073, P12074, O15239, Q16718, O14521

TNF, GSK3B, BCL2L11, ATF4, FASLG, ERN1, IL1B, COX4I1, COX6A1, NDUFA1, NDUFA5, SDHD

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
P14416	DRD2	D(2) dopamine receptor	P01375	TNF	Tumor necrosis factor	-0.767
P31645	SLC6A4	Sodium-dependent serotonin transporter	P49841	GSK3B	Glycogen synthase kinase-3 beta	-0.714
P14416	DRD2	D(2) dopamine receptor	P49841	GSK3B	Glycogen synthase kinase-3 beta	-0.812
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O43521	BCL2L11	Bcl-2-like protein 11	0.754
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.776
P14416	DRD2	D(2) dopamine receptor	P48023	FASLG	Tumor necrosis factor ligand superfamily member 6	0.7
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O75460	ERN1	Serine/threonine-protein kinase/endoribonuclease IRE1	0.733
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P01584	IL1B	Interleukin-1 beta	0.827
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P01584	IL1B	Interleukin-1 beta	0.762
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.7
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.778
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.782
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.847
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.916
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.721
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16718	NDUFA5	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5	0.757
P31645	SLC6A4	Sodium-dependent serotonin transporter	O14521	SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	0.732

Diphenoxylate

hsa04933

AGE-RAGE signaling pathway in diabetic complications

2.93E-03

P84022, Q13485, P10415, P42338, P49767, P17252, P19174

SMAD3, SMAD4, BCL2, PIK3CB, VEGFC, PRKCA, PLCG1

Diphenoxylate

hsa04934

Cushing syndrome

3.48E-03

Q99941, P51828, O15169, Q13557

CREBL1, ADCY7, AXIN1, CAMK2D

Diphenoxylate

hsa04940

Type I diabetes mellitus

1.87E-02

P48023, P01375

FASLG, TNF

Diphenoxylate

hsa04950

Maturity onset diabetes of the young

2.03E-02

P35557

GCK

Diphenoxylate

hsa04964

Proximal tubule bicarbonate reclamation

4.48E-02

P00918

CA2

Diphenoxylate

hsa04966

Collecting duct acid secretion

2.19E-03

P02730, P00918, Q9Y666

SLC4A1, CA2, SLC12A7

Diphenoxylate

hsa04970

Salivary secretion

8.71E-04

Q14643, P20020, P23634, P17252, P0DP23

ITPR1, ATP2B1, ATP2B4, PRKCA, CALM1

Diphenoxylate

hsa04971

Gastric acid secretion

1.87E-03

P51828, P17252, P15311, P63261, P0DP23, Q13557

ADCY7, PRKCA, VIL2, ACTG1, CALM1, CAMK2D

Diphenoxylate

hsa04972

Pancreatic secretion

1.00E-02

Q14643, P20020, P17252

ITPR1, ATP2B1, PRKCA

Diphenoxylate

hsa04973

Carbohydrate digestion and absorption

1.29E-02

O43451, P42338

MGAM, PIK3CB

Diphenoxylate

hsa04975

Fat digestion and absorption

2.80E-02

O14494

PLPP1

Diphenoxylate

hsa04976

Bile secretion

1.67E-03

O43315, P22694, P08183

AQP9, PRKACB, ABCB1

Diphenoxylate

hsa04978

Mineral absorption

3.94E-02

P23634, Q9BXS9

ATP2B4, SLC26A6

Diphenoxylate

hsa05010

Alzheimer disease

5.81E-05

Q92542, O15239, P05496, P13073, P12074, Q00535, O75460, P0DP23, P01584, O95197, P18848, O15169, P67870, P05141, P45880, P28070, P43686

NCSTN, NDUFA1, ATP5G1, COX4I1, COX6A1, CDK5, ERN1, CALM1, IL1B, RTN3, ATF4, AXIN1, CSNK2B, SLC25A5, VDAC2, PSMB4, PSMC4

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
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q92542	NCSTN	Nicastrin	0.706
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.916
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.721
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.842
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.733
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.7
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.778
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.782
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.754
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.847
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	Q00535	CDK5	Cyclin-dependent-like kinase 5	0.783
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	O75460	ERN1	Serine/threonine-protein kinase/endoribonuclease IRE1	0.731
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O75460	ERN1	Serine/threonine-protein kinase/endoribonuclease IRE1	0.733
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P0DP23	CALM1	Calmodulin-1	0.762
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P01584	IL1B	Interleukin-1 beta	0.827
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P01584	IL1B	Interleukin-1 beta	0.75
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P01584	IL1B	Interleukin-1 beta	0.762
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	O95197	RTN3	Reticulon-3	0.702
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.776
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	O15169	AXIN1	Axin-1	0.742
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P67870	CSNK2B	Casein kinase II subunit beta	0.709
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05141	SLC25A5	ADP/ATP translocase 2	0.75
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P45880	VDAC2	Voltage-dependent anion-selective channel protein 2	0.708
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P28070	PSMB4	Proteasome subunit beta type-4	0.735
P62942	FKBP1A	Peptidyl-prolyl cis-trans isomerase FKBP1A	P28070	PSMB4	Proteasome subunit beta type-4	0.778
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P43686	PSMC4	26S proteasome regulatory subunit 6B	0.804

Diphenoxylate

hsa05012

Parkinson disease

2.03E-03

O15239, P13073, P12074, P05496, P05141, P18848, P28070, P43686, Q13557

NDUFA1, COX4I1, COX6A1, ATP5G1, SLC25A5, ATF4, PSMB4, PSMC4, CAMK2D

Diphenoxylate

hsa05014

Amyotrophic lateral sclerosis

4.35E-04

O15399, P10415, P20333, O15239, P13073, P12074, P05496, P18848, Q13509, P68371, P28070, P43686, Q53GS7, P35658, P63261, Q9UBU9, Q9GZY0

GRIN2D, BCL2, TNFRSF1B, NDUFA1, COX4I1, COX6A1, ATP5G1, ATF4, TUBB3, TUBB2C, PSMB4, PSMC4, GLE1, NUP214, ACTG1, NXF1, NXF2; NXF2B

Diphenoxylate

hsa05016

Huntington disease

4.15E-06

O15239, P13073, P12074, P05496, Q9GZM3, P24928, P62487, P52435, P05141, Q9NYC9, P28070, P43686

NDUFA1, COX4I1, COX6A1, ATP5G1, POLR2J2, POLR2A, POLR2G, POLR2J, SLC25A5, DNAH9, PSMB4, PSMC4

Diphenoxylate

hsa05020

Prion disease

2.01E-06

P01584, P46531, P11142, O15239, Q16718, O14521, P05496, P13073, P12074, P18848, P05141, P45880, P28070, P43686, P49841, P51636, Q99941, Q16539

IL1B, NOTCH1, HSPA8, NDUFA1, NDUFA5, SDHD, ATP5G1, COX4I1, COX6A1, ATF4, SLC25A5, VDAC2, PSMB4, PSMC4, GSK3B, CAV2, CREBL1, 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
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P01584	IL1B	Interleukin-1 beta	0.827
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P01584	IL1B	Interleukin-1 beta	0.75
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P46531	NOTCH1	Neurogenic locus notch homolog protein 1	1
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P46531	NOTCH1	Neurogenic locus notch homolog protein 1	0.706
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.766
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.916
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16718	NDUFA5	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5	0.757
P31645	SLC6A4	Sodium-dependent serotonin transporter	O14521	SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	0.732
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.842
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.733
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.7
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.782
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.754
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.776
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05141	SLC25A5	ADP/ATP translocase 2	0.75
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	P45880	VDAC2	Voltage-dependent anion-selective channel protein 2	0.708
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P28070	PSMB4	Proteasome subunit beta type-4	0.735
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P43686	PSMC4	26S proteasome regulatory subunit 6B	0.804
P31645	SLC6A4	Sodium-dependent serotonin transporter	P49841	GSK3B	Glycogen synthase kinase-3 beta	-0.714
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P51636	CAV2	Caveolin-2	-0.709
P49354	FNTA	Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha	Q99941	CREBL1	Cyclic AMP-dependent transcription factor ATF-6 beta	0.769
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16539	MAPK14	Mitogen-activated protein kinase 14	-0.744

Diphenoxylate

hsa05022

Pathways of neurodegeneration - multiple diseases

7.82E-05

P49841, O15239, Q16718, O14521, P13073, P12074, P05496, P18848, Q13561, P05141, P20333, Q16539, P01584, Q08752, Q13557, P28070, P43686

GSK3B, NDUFA1, NDUFA5, SDHD, COX4I1, COX6A1, ATP5G1, ATF4, DCTN2, SLC25A5, TNFRSF1B, MAPK14, IL1B, PPID, CAMK2D, PSMB4, PSMC4

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
P31645	SLC6A4	Sodium-dependent serotonin transporter	P49841	GSK3B	Glycogen synthase kinase-3 beta	-0.714
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	O15239	NDUFA1	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1	0.916
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16718	NDUFA5	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5	0.757
P31645	SLC6A4	Sodium-dependent serotonin transporter	O14521	SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	0.732
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P13073	COX4I1	Cytochrome c oxidase subunit 4 isoform 1, mitochondrial	0.7
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P12074	COX6A1	Cytochrome c oxidase subunit 6A1, mitochondrial	0.782
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05496	ATP5G1	ATP synthase F(0) complex subunit C1, mitochondrial	0.842
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.776
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q13561	DCTN2	Dynactin subunit 2	-0.771
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05141	SLC25A5	ADP/ATP translocase 2	0.75
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P20333	TNFRSF1B	Tumor necrosis factor receptor superfamily member 1B	0.711
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16539	MAPK14	Mitogen-activated protein kinase 14	-0.744
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P01584	IL1B	Interleukin-1 beta	0.827
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q08752	PPID	Peptidyl-prolyl cis-trans isomerase D	0.859
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.784
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P28070	PSMB4	Proteasome subunit beta type-4	0.735
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P43686	PSMC4	26S proteasome regulatory subunit 6B	0.804

Diphenoxylate

hsa05031

Amphetamine addiction

1.49E-02

O15399, P0DP23, Q16566, P17252

GRIN2D, CALM1, CAMK4, PRKCA

Diphenoxylate

hsa05034

Alcoholism

2.05E-05

Q13547, Q93077, P58876, P62807, Q16778, O60814, P68431

HDAC1, HIST1H2AC, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12

Diphenoxylate

hsa05100

Bacterial invasion of epithelial cells

4.50E-02

Q92529

SHC3

Diphenoxylate

hsa05110

Vibrio cholerae infection

4.78E-02

Q99437

ATP6V0B

Diphenoxylate

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

2.62E-04

Q16539, P09341, P19875, P19174, P25024, P25025, P07948

MAPK14, CXCL1, CXCL2, PLCG1, CXCR1, CXCR2, LYN

Diphenoxylate

hsa05130

Pathogenic Escherichia coli infection

7.39E-03

Q14247, P56750, O00501, P25116

CTTN, CLDN17, CLDN5, F2R

Diphenoxylate

hsa05132

Salmonella infection

1.18E-05

P51617, Q9UJU2, P63261, Q13546, Q13489, P10415, O75369, O60603, Q9BQS8, P51808, Q13561, O60282, Q13509, P68371

IRAK1, LEF1, ACTG1, RIPK1, BIRC3, BCL2, FLNB, TLR2, FYCO1, DYNLT3, DCTN2, KIF5C, TUBB3, TUBB2C

Diphenoxylate

hsa05133

Pertussis

2.04E-05

P0DP23, P23528, P09871, P0C0L4, Q02556

CALM1, CFL1, C1S, C4A, IRF8

Diphenoxylate

hsa05134

Legionellosis

1.29E-02

P11215, P11142, P09341, P19875

ITGAM, HSPA8, CXCL1, CXCL2

Diphenoxylate

hsa05135

Yersinia infection

4.65E-02

P13612, P06239, Q16539, P01375, P49841

ITGA4, LCK, MAPK14, TNF, GSK3B

Diphenoxylate

hsa05140

Leishmaniasis

5.31E-07

P13612, O75015, P14598, P23458, P42224, P13765, O60603, P25963, P01375, P01584, P29350, P49006, Q16539, P51617, Q15080

ITGA4, FCGR3B, NCF1, JAK1, STAT1, HLA-DOB, TLR2, NFKBIA, TNF, IL1B, PTPN6, MARCKSL1, MAPK14, IRAK1, 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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13612	ITGA4	Integrin alpha-4	-0.771
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P14598	NCF1	Neutrophil cytosol factor 1	0.711
P51684	CCR6	C-C chemokine receptor type 6	P14598	NCF1	Neutrophil cytosol factor 1	-0.713
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.714
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P51684	CCR6	C-C chemokine receptor type 6	O60603	TLR2	Toll-like receptor 2	-0.767
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.865
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P01375	TNF	Tumor necrosis factor	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P29350	PTPN6	Tyrosine-protein phosphatase non-receptor type 6	0.856
P51684	CCR6	C-C chemokine receptor type 6	P49006	MARCKSL1	MARCKS-related protein	0.727
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.71
P51684	CCR6	C-C chemokine receptor type 6	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	0.722
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q15080	NCF4	Neutrophil cytosol factor 4	0.764
P51684	CCR6	C-C chemokine receptor type 6	Q15080	NCF4	Neutrophil cytosol factor 4	-0.803

Diphenoxylate

hsa05143

African trypanosomiasis

2.72E-02

P01375, P48023

TNF, FASLG

Diphenoxylate

hsa05144

Malaria

6.54E-06

P60033, O60603, P01375, P35443, P01584, P26718

CD81, TLR2, TNF, THBS4, IL1B, KLRK1

Diphenoxylate

hsa05146

Amoebiasis

6.98E-07

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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09341	CXCL1	Growth-regulated alpha protein	0.781
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14778	IL1R1	Interleukin-1 receptor type 1	0.762
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05089	ARG1	Arginase-1	0.811
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.779
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08311	CTSG	Cathepsin G	0.709

Diphenoxylate

hsa05150

Staphylococcus aureus infection

1.31E-02

P0C0L4, P13646

C4A, KRT13

Diphenoxylate

hsa05152

Tuberculosis

8.00E-03

Q99437, P13473, P42224, P48382, P25208, P01375, P25774, P49913, P51617

ATP6V0B, LAMP2, STAT1, RFX5, NFYB, TNF, CTSS, CAMP, IRAK1

Diphenoxylate

hsa05160

Hepatitis C

1.27E-02

P60033, P49841, P01375, P48023

CD81, GSK3B, TNF, FASLG

Diphenoxylate

hsa05163

Human cytomegalovirus infection

1.60E-03

P01375, P63218, P50151, P0DP23, Q8NHW4, Q08828, P23458, P49841, P14778, P01584, P61073, Q13651, P25025, Q16539, O00463

TNF, GNG5, GNG10, CALM1, CCL4L2, ADCY1, JAK1, GSK3B, IL1R1, IL1B, CXCR4, IL10RA, CXCR2, MAPK14, TRAF5

Diphenoxylate

hsa05168

Herpes simplex virus 1 infection

1.94E-02

Q9UKJ0, P01568, Q9GZY0, Q01130, Q13489, Q13398, Q03923, Q9UDV6, P10415

PILRB, IFNA21, NXF2; NXF2B, SFRS2, BIRC3, ZNF211, ZNF85, ZNF212, BCL2

Diphenoxylate

hsa05169

Epstein-Barr virus infection

2.54E-02

Q92769, P04637, Q13546, P10415, P24522, O60603, P51617, P09693

HDAC2, TP53, RIPK1, BCL2, GADD45A, TLR2, IRAK1, CD3G

Diphenoxylate

hsa05170

Human immunodeficiency virus 1 infection

3.76E-04

P62873, P0DP23, P01375, P17252, Q13546, Q14643, P51617, P25963, O60603, Q13315, Q9NQU5, P09693, P10415, Q93034, Q9Y6Q5, P20333

GNB1, CALM1, TNF, PRKCA, RIPK1, ITPR1, IRAK1, NFKBIA, TLR2, ATM, PAK6, CD3G, BCL2, CUL5, AP1M2, TNFRSF1B

Diphenoxylate

hsa05171

Coronavirus disease - COVID-19

2.46E-04

P01375, P01584, P51617, P25963, P42224, P23396, P62753, P39019, P42677, Q02878, P62917, P27635, Q07020, P61513, P63173, P05386, P04141

TNF, IL1B, IRAK1, NFKBIA, STAT1, RPS3, RPS6, RPS19, RPS27, RPL6, RPL8, RPL10, RPL18, RPL37A, RPL38, RPLP1, CSF2

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
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P01375	TNF	Tumor necrosis factor	0.711
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P01584	IL1B	Interleukin-1 beta	0.827
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.71
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.865
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.714
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P23396	RPS3	40S ribosomal protein S3	0.777
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P23396	RPS3	40S ribosomal protein S3	0.701
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P62753	RPS6	40S ribosomal protein S6	0.721
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P39019	RPS19	40S ribosomal protein S19	0.7
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P39019	RPS19	40S ribosomal protein S19	0.733
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P42677	RPS27	40S ribosomal protein S27	0.738
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	Q02878	RPL6	60S ribosomal protein L6	0.753
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P62917	RPL8	60S ribosomal protein L8	0.763
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P62917	RPL8	60S ribosomal protein L8	0.814
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P27635	RPL10	60S ribosomal protein L10	0.708
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	Q07020	RPL18	60S ribosomal protein L18	0.732
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	Q07020	RPL18	60S ribosomal protein L18	0.722
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P61513	RPL37A	60S ribosomal protein L37a	0.787
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P63173	RPL38	60S ribosomal protein L38	0.742
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P05386	RPLP1	60S acidic ribosomal protein P1	0.777
P46531	NOTCH1	Neurogenic locus notch homolog protein 1	P05386	RPLP1	60S acidic ribosomal protein P1	0.781
Q9UM47	NOTCH3	Neurogenic locus notch homolog protein 3	P04141	CSF2	Granulocyte-macrophage colony-stimulating factor	-0.749

Diphenoxylate

hsa05200

Pathways in cancer

5.18E-04

Q13751, P42338, P08238, P19174, Q9UJU2, P17252, P43246, P84022, Q13485, Q13547, P14923, P30281, P10415, Q13489, P49767, P43657, P25116, P63218, P50151, Q14344, Q7LDG7, P78417, O75293, P0DP23, P01568, P14784

LAMB3, PIK3CB, HSP90AB1, PLCG1, LEF1, PRKCA, MSH2, SMAD3, SMAD4, HDAC1, JUP, CCND3, BCL2, BIRC3, VEGFC, P2RY5, F2R, GNG5, GNG10, GNA13, RASGRP2, GSTO1, 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
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
P46091	GPR1	Chemerin-like receptor 2	Q9UJU2	LEF1	Lymphoid enhancer-binding factor 1	0.736
P46091	GPR1	Chemerin-like receptor 2	P17252	PRKCA	Protein kinase C alpha type	0.741
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43246	MSH2	DNA mismatch repair protein Msh2	-0.811
P46091	GPR1	Chemerin-like receptor 2	P43246	MSH2	DNA mismatch repair protein Msh2	-0.838
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
P46091	GPR1	Chemerin-like receptor 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.809
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13547	HDAC1	Histone deacetylase 1	-0.754
P46091	GPR1	Chemerin-like receptor 2	P14923	JUP	Junction plakoglobin	0.883
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743
P46091	GPR1	Chemerin-like receptor 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.808
P46091	GPR1	Chemerin-like receptor 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.759
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P46091	GPR1	Chemerin-like receptor 2	P49767	VEGFC	Vascular endothelial growth factor C	0.718
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P46091	GPR1	Chemerin-like receptor 2	P25116	F2R	Proteinase-activated receptor 1	0.76
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
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
P46091	GPR1	Chemerin-like receptor 2	P78417	GSTO1	Glutathione S-transferase omega-1	0.738
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	0.731
P46091	GPR1	Chemerin-like receptor 2	P0DP23	CALM1	Calmodulin-1	-0.846
P46091	GPR1	Chemerin-like receptor 2	P01568	IFNA21	Interferon alpha-21	0.724
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835

Diphenoxylate

hsa05202

Transcriptional misregulation in cancer

1.68E-06

P41732, P17844, P14780, P27930, Q15744, Q16548, P11215, Q13077, P35226, P05164, P12838, P08246, Q9C0K0, P41182, Q13547, Q92769, P12980, P24522

TSPAN7, DDX5, MMP9, IL1R2, CEBPE, BCL2A1, ITGAM, 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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41732	TSPAN7	Tetraspanin-7	0.703
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14780	MMP9	Matrix metalloproteinase-9	0.942
O15245	SLC22A1	Solute carrier family 22 member 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.711
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16548	BCL2A1	Bcl-2-related protein A1	0.913
O15245	SLC22A1	Solute carrier family 22 member 1	P11215	ITGAM	Integrin alpha-M	0.706
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13077	TRAF1	TNF receptor-associated factor 1	-0.712
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P05164	MPO	Myeloperoxidase	0.719
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P12838	DEFA4	Neutrophil defensin 4	0.784
P14780	MMP9	Matrix metalloproteinase-9	P12838	DEFA4	Neutrophil defensin 4	0.858
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12838	DEFA4	Neutrophil defensin 4	0.767
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P08246	ELA2	Neutrophil elastase	0.702
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.765
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41182	BCL6	B-cell lymphoma 6 protein	0.9
O15245	SLC22A1	Solute carrier family 22 member 1	Q13547	HDAC1	Histone deacetylase 1	-0.711
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13547	HDAC1	Histone deacetylase 1	-0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13547	HDAC1	Histone deacetylase 1	-0.742
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q92769	HDAC2	Histone deacetylase 2	-0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q92769	HDAC2	Histone deacetylase 2	-0.746
O15245	SLC22A1	Solute carrier family 22 member 1	P12980	LYL1	Protein lyl-1	0.806
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P12980	LYL1	Protein lyl-1	0.784
P14780	MMP9	Matrix metalloproteinase-9	P12980	LYL1	Protein lyl-1	0.716
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12980	LYL1	Protein lyl-1	0.782
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.801

Diphenoxylate

hsa05203

Viral carcinogenesis

1.22E-03

Q13547, Q15283, P58876, P62807, Q16778, O60814

HDAC1, RASA2, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12

Diphenoxylate

hsa05204

Chemical carcinogenesis

1.48E-02

P78417, P11712

GSTO1, CYP2C9

Diphenoxylate

hsa05206

MicroRNAs in cancer

2.97E-03

P15311, P21860, P61978, P46531, P63279, P22105

VIL2, ERBB3, HNRPK, NOTCH1, UBE2I, TNXB

Diphenoxylate

hsa05212

Pancreatic cancer

9.39E-03

P42338, P37173, P84022, Q13485, O75293

PIK3CB, TGFBR2, SMAD3, SMAD4, GADD45B

Diphenoxylate

hsa05214

Glioma

8.71E-04

P0DP23, Q16566, P17252, P04637, P24522

CALM1, CAMK4, PRKCA, TP53, GADD45A

Diphenoxylate

hsa05216

Thyroid cancer

1.85E-02

Q9UJU2, P04637, P24522

LEF1, TP53, GADD45A

Diphenoxylate

hsa05217

Basal cell carcinoma

4.48E-03

Q13635, P49841, Q9UJU2, P04637, P24522

PTCH1, GSK3B, LEF1, TP53, GADD45A

Diphenoxylate

hsa05220

Chronic myeloid leukemia

2.16E-02

Q13547, Q13485, P84022, P42338, O75293

HDAC1, SMAD4, SMAD3, PIK3CB, GADD45B

Diphenoxylate

hsa05235

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

1.58E-03

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

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

Diphenoxylate

hsa05310

Asthma

2.81E-02

P13765, P12724, P01375

HLA-DOB, RNASE3, TNF

Diphenoxylate

hsa05321

Inflammatory bowel disease

1.52E-06

O60603, P01375, P13765, Q14765, Q9UL17, P23771, P01584

TLR2, TNF, HLA-DOB, STAT4, TBX21, GATA3, IL1B

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	O60603	TLR2	Toll-like receptor 2	0.842
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.768
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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UL17	TBX21	T-box transcription factor TBX21	-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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807

Diphenoxylate

hsa05322

Systemic lupus erythematosus

4.80E-06

P09871, Q93077, P58876, P62807, Q16778, O60814, P68431

C1S, HIST1H2AC, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12

Diphenoxylate

hsa05330

Allograft rejection

2.72E-02

P48023, P01375

FASLG, TNF

Diphenoxylate

hsa05332

Graft-versus-host disease

3.14E-04

P13765, P48023, P01375, P26715, Q13241

HLA-DOB, FASLG, TNF, KLRC1, KLRD1

Diphenoxylate

hsa05412

Arrhythmogenic right ventricular cardiomyopathy

4.48E-02

P54284

CACNB3

Diphenoxylate

hsa05414

Dilated cardiomyopathy

4.55E-02

P54284, P26678

CACNB3, PLN

Diphenoxylate

hsa05415

Diabetic cardiomyopathy

4.30E-04

P05141, O15239, Q16718, O14521, P05496, P13073, P12074, Q16539, P49841, Q13557

SLC25A5, NDUFA1, NDUFA5, SDHD, ATP5G1, COX4I1, COX6A1, MAPK14, GSK3B, CAMK2D

Diphenoxylate

hsa05418

Fluid shear stress and atherosclerosis

2.49E-03

Q16539, P78417, P10599, P14780, P01375, P63261, P10415, P14778, P27930, P0DP23, Q92974

MAPK14, GSTO1, TXN, MMP9, TNF, ACTG1, BCL2, IL1R1, IL1R2, CALM1, ARHGEF2

Community members of Diphenoxylate (S_DC: 7.43)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

KCNA3

Potassium voltageNonegated channel subfamily A member 3

Predicted

0.1396

0.5055

1.0809

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P31645

SLC6A4

SodiumNonedependent serotonin transporter

Predicted

0.0477

0.0203

2.0442

P14416

DRD2

D(2) dopamine receptor

Predicted

0.0604

0.4779

2.5081

P30531

SLC6A1

SodiumNone and chlorideNonedependent GABA transporter 1

Predicted

0.0889

0.5202

0.1047

1.1894

P14780

MMP9

Matrix metalloproteinaseNone9

Predicted

0.1696

0.8424

0.7315

2.5012

P21730

C5AR1

C5a anaphylatoxin chemotactic receptor 1

Predicted

0.0258

0.2167

0.5396

0.986

Q13547

HDAC1

Histone deacetylase 1

Predicted

0.0447

0.986

3.0084

P09619

PDGFRB

PlateletNonederived growth factor receptor beta

Predicted

0.0496

0.9444

0.7408

2.6543

P09917

ALOX5

Polyunsaturated fatty acid 5Nonelipoxygenase

Predicted

0.3822

0.2701

2.4612

P18054

ALOX12

Polyunsaturated fatty acid lipoxygenase ALOX12

Predicted

0.0075

0.3703

0.2416

0.986

Q92769

HDAC2

Histone deacetylase 2

Predicted

0.0473

0.986

3.0097

P08183

ABCB1

ATPNonedependent translocase ABCB1

Predicted

0.0788

0.2052

2.2446

P11712

CYP2C9

Cytochrome P450 2C9

Predicted

0.0106

0.1524

2.1577

P10826

RARB

Retinoic acid receptor beta

Predicted

0.0094

0.3466

0.3005

0.9983

P49354

FNTA

Protein farnesyltransferase/geranylgeranyltransferase typeNone1 subunit alpha

Predicted

0.5303

0.7588

1.7827

P09874

PARP1

Poly [ADPNoneribose] polymerase 1

Predicted

0.5536

0.4482

2.725

Q13822

ENPP2

Ectonucleotide pyrophosphatase/phosphodiesterase family member 2

Predicted

0.113

0.305

0.0063

0.6729

P62942

FKBP1A

PeptidylNoneprolyl cisNonetrans isomerase FKBP1A

Predicted

0.432

0.2695

0.7551

O15245

SLC22A1

Solute carrier family 22 member 1

Predicted

0.0149

0.0219

2.0294

Q02763

TEK

AngiopoietinNone1 receptor

Predicted

0.3206

0.6236

0.4304

1.8379

P43490

PBEF1

Nicotinamide phosphoribosyltransferase

Predicted

0.4423

0.7064

0.238

1.872

P08235

NR3C2

Mineralocorticoid receptor

Predicted

0.1855

0.0137

2.1064

P46531

NOTCH1

Neurogenic locus notch homolog protein 1

Predicted

0.4407

0.0222

0.5047

0.7694

Q9UM47

NOTCH3

Neurogenic locus notch homolog protein 3

Predicted

0.3529

0.0222

0.4868

0.7077

P35610

SOAT1

Sterol ONoneacyltransferase 1

Predicted

0.3855

0.2936

0.0165

0.7964

P25774

CTSS

Cathepsin S

Predicted

0.3185

0.4932

0.5168

1.6625

Q02750

MAP2K1

Dual specificity mitogenNoneactivated protein kinase kinase 1

Predicted

0.312

0.5129

2.1819

P21462

FPR1

fMetNoneLeuNonePhe receptor

Predicted

0.1205

0.3492

0.4378

1.1964

P25025

CXCR2

CNoneXNoneC chemokine receptor type 2

Predicted

0.0278

0.5189

0.4494

1.5011

P25024

CXCR1

CNoneXNoneC chemokine receptor type 1

Predicted

0.1656

0.4232

0.4009

1.33

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P51684

CCR6

CNoneC chemokine receptor type 6

Predicted

0.085

0.1741

0.3304

0.7212

P46091

GPR1

ChemerinNonelike receptor 2

Predicted

0.2476

0.1372

0.3982

PharmaCoNets of Diphenoxylate (SPCN: 157.32 )

Diphenoxylate regulated-network (SDN: 21.17)

Community members of Diphenoxylate (SDC: 7.43)

PharmaCoNets of Diphenoxylate (S_PCN: 157.32 )

Diphenoxylate regulated-network (S_DN: 21.17)

Community members of Diphenoxylate (S_DC: 7.43)