Bioinformatics analysis of candidate genes and potential therapeutic drugs targeting adipose tissue in obesity

Figures & data

Figure 1. Differentially expressed genes (DEGs) between the obesity and control cohorts. Volcano plot of GSE133099 and 11 substantially expressed genes were detected. Black, green, and red dots represent unchanged, downregulated, and upregulated genes, in that order

Table 1. Significantly enriched GO terms in obesity-related DEGs

Category	Term	Genes	FDR
BP	Extracellular matrix organization	ITGB1, EGFL6, HPSE2, ELN, FN1, MFAP5, CCDC80, COL1A2, COL5A1, LOX, COL4A4, COL6A2, COL4A3, COL6A3, ITGA5, RECK	0.003150327
	Extracellular fibril organization	MFAP5, CST3, MFAP4, COL5A1, LTBP2	0.033994008
CC	Proteinaceous extracellular matrix	WNT2B, HPSE2, ELN, LTBP2, PRELP, FBLN2, ADAMTS10, GLG1, WISP2, PTPRZ1, CHL1, TIMP2, ADAMTS9, WNT3, CRTAP, FN1, MMP13, COL1A2, COL5A1, LOX, CILP, COL4A4, COL6A2, COL4A3, MGP, COL6A3, CHI3L1, MMP19, CD248, GPLD1	2.65E-13
CC	Extracellular exosome	SCARB2, CLIC6, ITGB1, HSP90AB1, GALNT16, GDA, PROS1, DNHD1, PTPRJ, SLC2A5, WISP2, SCPEP1, UCHL1, ISLR, LAMP1, CHL1, GLIPR2, NCS1, TIMP2, QSOX1, PTGDS, EDIL3, CACNA2D1, IL18, RENBP, PSMA6, ALDH1A3, COL6A2, CMPK1, COL6A3, CHI3L1, DNASE2, MFGE8, GPLD1, RHOQ, ANGPTL1, PLBD2, ASAH1, SLC22A5, C1S, NPR3, SEMA3G, PRELP, LTBP2, SLC1A4, LIN7A, PDHB, SDSL, NDRG2, FBLN2, GNS, THBS4, ACACA, GLG1, CST3, CLEC3B, SCIN, PDLIM2, PSAP, SH3BP4, ST3GAL6, IGFBP6, MAP4, APOE, SIAE, WNT3, GSTM3, FN1, DSTN, CDC42BPB, TUBB4B, ASS1, RAB11A, PTPRD, MFAP4, BST1, FMNL1, COL1A2, COL5A1, TCN2, MAN2B2, GLB1, CILP, FAM151A, XPNPEP2, MGP, APOC1, CD248, NUCB2	9.44E-08
	Extracellular region	LY6K, ADAMDEC1, CSF2, WNT2B, ELN, PROS1, ANTXR2, CHRDL1, LFNG, ISLR, GLIPR2, TMSB4X, TIMP2, QSOX1, PTGDS, IGFBP5, IL18, MR1, MMP13, LOX, COL4A4, COL6A2, COL4A3, COL6A3, HHIPL1, MMP19, MFGE8, HBEGF, ITIH5, NOTCH3, COLEC10, C1S, NXPH4, PRELP, SEMA3E, FBLN2, THBS4, SCUBE2, CST3, CLEC3B, FRZB, PSAP, PENK, FAM180A, IGFBP6, APOE, C11ORF45, PLTP, WNT3, ANGPT4, NMB, FN1, PRSS35, BMP6, MFAP5, MFAP4, COL1A2, COL5A1, TCN2, LEP, APOC1	1.38E-07
	Extracellular matrix	FN1, PRELP, LTBP2, TUBB4B, FBLN2, ADAMTS10, THBS4, MFAP4, CLEC3B, MMP13, COL1A2, COL5A1, CILP, COL6A2, MGP, TIMP2, MMP19, COL6A3, APOE, MFGE8, EDIL3, ADAMTS9	1.60E-06
	Extracellular vesicle	LFNG, OLFML3, COL6A2, COL6A3, PRELP, APOE, MFGE8, TUBB4B, EDIL3, FBLN2	6.09E-06
	Extracellular space	CSF2, WNT2B, PROS1, WISP2, TIMP2, QSOX1, PTGDS, ADAMTS9, EGFL6, METRN, IL18, MMP13, LOX, COL6A2, COL6A3, CHI3L1, MFGE8, GPLD1, ANGPTL1, HBEGF, ASAH1, GCNT1, SEMA3G, PRELP, LTBP2, SEMA3E, THBS4, CST3, CLEC3B, FRZB, PSAP, IGFBP6, APOE, SIAE, PLTP, WNT3, ANGPT4, CRTAP, FN1, SULF1, BMP6, COL1A2, TCN2, GLB1, CILP, VNN3, LEP, NUCB2, CCL26	1.51E-05
	Lysosomal lumen	SCARB2, ASAH1, TCN2, GLB1, MAN2B2, PSAP, PRELP, GNS, PLBD2	0.003123445
	Collagen trimer	COLEC10, MMP13, COL1A2, COL5A1, LOX, COL4A4, COL6A2, COL4A3, COL6A3	0.00478510818157352
	Endoplasmic reticulum lumen	CRTAP, STS, COL1A2, ERAP2, COL5A1, COL4A4, COL6A2, COL4A3, CERCAM, P3H2, COL6A3, WNT3	0.010883682
MF	Integrin binding	ADAMDEC1, ADAM32, MMP8, MMP9, ADAM18, ADAMTS3, KEL, MMP16, FAP, MMP26, CLCA1, TLL1, CLCA4	4.65E-04
	Extracellular matrix structural constituent	OAS1, OAS2, OAS3, OASL	4.65E-04

Table 2. Significantly enriched pathways in obesity-related DEGs

Pathway ID	Name	Genes	P-Value
hsa04512	ECM-receptor interaction	ITGB1, COL1A2, COL5A1, COL4A4, COL6A2, COL4A3, FN1, COL6A3, ITGA5, THBS4	2.86E-05
hsa04510	Focal adhesion	ITGB1, FN1, THBS4, COL1A2, CCND2, COL5A1, COL4A4, COL6A2, COL4A3, ERBB2, COL6A3, FYN, ITGA5	3.94E-04
hsa04974	Protein digestion and absorption	COL1A2, COL5A1, XPNPEP2, COL4A4, ELN, COL6A2, COL4A3, COL6A3	0.001138329
hsa04151	PI3K-Akt signalling pathway	ITGB1, ANGPT4, CSF1R, HSP90AB1, FN1, THBS4, COL1A2, CCND2, COL5A1, PPP2R2C, COL4A4, COL6A2, COL4A3, COL6A3, ITGA5	0.004374222
hsa04142	Lysosome	SCARB2, ASAH1, LAMP1, GLB1, PSAP, DNASE2, ABCB9, GNS	0.00686595
hsa05205	Proteoglycans in cancer	ITGB1, WNT2B, HPSE2, ERBB2, FN1, TWIST1, ITPR3, ITGA5, WNT3, HBEGF	0.011432848
hsa05204	Chemical carcinogenesis	SULT1A1, GSTM3, ALDH1A3, ADH4, GSTM5, SULT1A2	0.015821
hsa04924	Renin secretion	EDNRA, PDE3A, ITPR3, CACNA1C, KCNJ2	0.030065163
hsa05146	Amoebiasis	CSF2, COL1A2, COL5A1, COL4A4, COL4A3, FN1	0.045859559
hsa00531	Glycosaminoglycan degradation	HPSE2, GLB1, GNS	0.047121568

Figure 2. Biological functions based on Gene Ontology (GO) analysis of obesity-related DEGs

Figure 3. KEGG pathway analysis of obesity-related DEGs

Table 3. Tissue-specific genes identified using BioGPS

System	Genes
Neurologic	EGFL6, ALDH1A3, MFAP4, IGFBP6, TSPAN13, GALNT17, PTGDS, CERCAM, MEF2C, SLC4A3, NDRG4, LTBP2, LTBP3, LMOD1, PENK, CHRDL1, UCHL1, PEG10, PPP2R2C, OLFML3, ITPR3, SGCE, CLIC6, PLTP, PURA, NPTX1, CHI3L1, CLIP2, TAGLN, CDR2L, SCRN1, CDC42BPB, THBS4, FBLN2, METRN, NDRG2, SCARB2, PEA15, SASH1, RBP1, FEZ1, C1S, PTPRD, PSD3, FN1, DYNC1LI2, UBE2QL1, PROS1, CD99L2, PTPRZ1, CHL1, PDE4D
Immune	TSPAN13, MEF2C, OSTM1, LTBP3, P3H2, ADCY7, ERAP2, CHRDL1, UCHL1, GYPC, ITPR3, SAMHD1, CLIC6, MCUB, GLB1, PDLIM1, CSF1R, APOC1, ELOVL6, CLIP2, RASSF5, SH3TC1, COL6A3, RAB6B, UNC13C, BST1, NUCB2, MZF1, NPR3, SFT2D1, SCRN1, GNS, NLRP1, NDRG2, SCARB2, SULT1A1, BCL7A, MAFB, CCND2, PBXIP1, CCNL1, MCM2, NKTR, SCPEP1, PDLIM2, MYL4, FYN, RGS2, REXO2, DDX39B, SMURF2
Genital	EGFL6, MFAP5, MFAP4, PALLD, CD248, LMOD1, PENK, CHRDL1, PEG10, CALD1, TEX26, OLFML3, ITPR3, PLTP, CSF1R, SLC2A5, CHI3L1, FRZB, TAGLN, CLEC3B, EMX2, COL6A3, LEP, PAEP, COL5A1, FBLN2, NOTCH3, TIMP2, RBP1, CCIN, C15orf48, C1S, PDLIM2, GSTM3, EDNRA, RGS2, GPNMB, TWIST1
Respiratory	EGFL6, ALDH1A3, MFAP4, TSPAN13, COL6A2, CCN5, ELN, SFTPA2, SFTPA1, LTBP3, ITPR3, PDLIM1, APOC1, ELOVL6, FRZB, BNC1, CLEC3B, NPR3, TCEAL9, COL5A1, TIMP2, FEZ1, C1, PDLIM2, PRELP, EDNRA, GPNMB, SMURF2
Digestive	ALDH1A3, IGFBP6, TSPAN13, PALLD, LTBP3, LMOD1, CILP, PEG10, SLC2A5, APOC1, SH3BP4, PNKD, COL6A3, APOE, ADAMDEC1, SULT1A1, RBP1, C15orf48, CASQ2, C1S, MYL4, RAB11A, FN1, PROS1, XPNPEP2, ADH7, ASS1
Circulatory	CCDC80, MFAP5, MFAP4, IGFBP6, PTGDS, LOX, SLC4A3, NDRG4, LTBP2, UCHL1, APOC1, TAGLN, SH3TC1, CLEC3B, MGP, ID3, COL1A2, SULF1, NEK7, COL5A1, FBLN2, MAFB, CASQ2, MYL4, FN1, GPNMB
Skeletal muscle	MFGE8, ALDH1A3, CCDC80, MFAP5, IGFBP6, FKBP9, CCN5, ITGB1, CD248, LOX, ELN, LTBP2, CILP, CHRDL1, OLFML3, SGCE, ELOVL6, SH3BP4, TAGLN, RECK, NPR3, COL1A2, SULF1, PTGFRN, MEDAG
Endocrine	TSPAN13, LTBP3, CA3, CHRDL1, UCHL1, ITPR3, CLIC6, PDLIM1, ASAH1, CLEC3B, COL6A3, MGP, NUCB2, ID3, CDC42BPB, TCEAL9, COL1A2, COL5A1, METRN, RBP1, MAFB, MCM2, SCPEP1, ISLR
Urinary	PALLD, ALDH1A3, PTGDS, NDRG4, LTBP3, LMOD1, P3H2, NOX4, TAGLN, PGAP1, GNS, SYT17, XPNPEP2, ASS1
Haematological	MFAP4, OSTM1, UCHL1, ITPR3, MCUB, SLC2A5, CHI3L1, CLIP2, PNKD, SFT2D1, MCM2, KCNJ2

Figure 4. Common hub genes based on Degree, Stress, and EcCentricity algorithm

Figure 5. Venn diagram showing the key genes involved in obese adipocyte samples

Table 4. Nine FDA-approved drugs potentially targeting the four key genes

Target Gene	Drug	Interaction Types	*Score
FYN	dasatinib	inhibitor|multitarget	8
FN1	ocriplasmin	cleavage	3
LEP	risperidone	NA	7
LEP	gemfibrozil	NA	3
APOE	ritonavir	NA	3
APOE	fluvastatin	NA	3
APOE	pravastatin	NA	3
APOE	warfarin	NA	3
APOE	atorvastatin	NA	5

*Score: The number of database sources and/or PubMed references supporting the drug-gene interaction.