Correlation and integration of circulating miRNA and peripheral whole blood gene expression profiles in patients with venous thromboembolism

Figures & data

Table 1. Top ten miRNAs with the most significant differential expressions in peripheral blood of VTE patients

miRNA ID	Adjusted ID	LogFC	P Value
hsa-miR-144*	hsa-miR-144-5p	−3.49593	0.0301
hsa-let-7 g	hsa-let-7 g-5p	−3.30413	0.0122
hsa-miR-20a*	hsa-miR-20a-3p	−3.08215	0.0144
hsa-miR-7	hsa-miR-7-5p	−2.95788	0.0144
hsa-miR-942	hsa-miR-942	−2.79764	0.0301
hsa-miR-874	hsa-miR-874	5.18195	0.0121
hsa-miR-522	hsa-miR-522-3p	5.07948	0.0476
hsa-miR-193a	hsa-miR-193a	3.62387	0.0121
hsa-miR-134	hsa-miR-134	3.56239	0.0121
hsa-miR-483	hsa-miR-483-3p	3.2528	0.0121

Table 2. Differentially expressed genes (DEGs) in peripheral blood of VTE patients

Gene.symbol	P Value	logFC	Gene.symbol	P Value	logFC	Gene.symbol	P Value	logFC
TLN1	0.002311	1.052952	HSP90AA1	0.002017	−1.80932	RPL31	0.005412	−1.92844
ZFP36L1	0.005728	1.152931	HSPE1-MOB4	0.012055	−1.34059	RPL34	0.009949	−1.4919
ACADM	0.011272	−1.08054	IFIT1	0.004666	−2.16111	RPL36A	0.015296	−1.58538
ACTR6	0.01149	−1.25503	IFIT5	0.005731	−1.10699	RPL36AL	0.001992	−1.25677
AGL	0.01416	−1.58293	IL6ST	0.015079	−1.04166	RPL39	0.006067	−1.33649
AK6	0.005524	−1.13278	IMPA1	0.014093	−1.28687	RPL41	0.006066	−1.03092
AKR1C3	0.005214	−1.33393	ITGAV	0.011772	−1.05021	RPL7	0.004045	−1.70641
ANKRD49	0.013643	−1.06019	JAK2	0.012256	−1.19741	RPL9	0.002887	−1.87196
ANP32E	0.013272	−1.39025	KIAA0391	0.002086	−1.61566	RPS15A	0.005669	−1.15386
ANXA1	0.003366	−1.53284	KLRB1	0.005296	−1.3837	RPS17	0.004258	−1.45516
ANXA3	0.014972	−1.25051	KLRF1	0.011312	−1.19703	RPS23	0.002284	−1.69922
ATAD2B	0.013658	−1.13958	KTN1	0.003373	−1.50054	RPS24	0.005425	−1.65096
ATG5	0.011539	−1.00773	LAMTOR3	0.014781	−1.29482	RPS27A	0.002842	−1.01885
ATP5C1	0.002023	−1.54041	LPAR6	0.001768	−1.71736	RPS27L	0.003608	−1.68584
ATP5F1	0.002086	−1.37046	LRRC40	0.013329	−1.16338	RPS7	0.003344	−2.08102
ATP5O	0.003169	−1.29712	LSM5	0.002711	−1.43599	RSL24D1	0.011772	−1.62669
ATP6V1C1	0.002693	−1.11276	LY96	0.011837	−1.15484	RWDD1	0.003345	−1.27051
ATP6V1D	0.001203	−1.1632	MBNL1	0.004213	−1.16926	SAMD9	0.00434	−1.18383
BCL2A1	0.010465	−1.7155	MBNL2	0.009319	−1.01842	SAR1B	0.003997	−1.15723
BIRC2	0.011542	−1.42805	MCTS1	0.001768	−1.3979	SEC62	0.012933	−1.152
C12orf29	0.005296	−1.21351	MDH1	0.001845	−1.19747	SH2D1A	0.004369	−1.34456
C14orf2	0.007742	−1.05559	MED21	0.001385	−1.34853	SKIV2L2	0.007982	−1.10264
C4orf46	0.009319	−1.36502	MRPL13	0.007877	−1.03596	SLC30A1	0.01449	−1.07211
CAPZA1	0.005565	−1.04274	MRPL15	0.001992	−1.14411	SMC4	0.012048	−1.323
CAPZA2	0.007171	−1.43103	MRPL3	0.003416	−1.46333	SNHG4	0.002842	−1.45734
CASP3	0.003645	−1.22233	MRPL42	0.003911	−1.20088	SNORA21	0.00596	−1.58185
CCDC91	0.006256	−1.24315	MS4A4A	0.007398	−1.36585	SNORD54	0.001992	−1.04649
CCNC	0.014805	−1.19752	MTHFD2	0.002228	−1.43667	SNORD73A	0.001992	−2.51606
CCT2	0.001768	−1.30835	MYBL1	0.00434	−1.55335	SNRPD2	0.002749	−1.51699
CD2AP	0.014103	−1.1228	MYL6	0.002056	−1.02559	SNRPG	0.01334	−1.2511
CD69	0.009904	−1.25466	NAA15	0.007877	−1.12972	SNX4	0.003147	−1.25499
CD86	0.001203	−1.17836	NAB1	0.011071	−1.08198	SRP19	0.002783	−1.09312
CEBPZ	0.002086	−1.38956	NAT1	0.007982	−1.03158	SRP72	0.001203	−1.14042
CEP57	0.003416	−1.18991	NDUFA1	0.002991	−1.1217	SSB	0.002086	−1.08434
CHD9	0.00717	−1.08933	NDUFA4	0.004017	−1.52358	STAG2	0.007282	−1.14388
CHMP5	0.007982	−1.1441	NDUFA5	0.015165	−1.42653	STX7	0.008636	−1.06838
CKS2	0.002887	−1.30107	NDUFA6	0.00251	−1.03084	SUB1	0.006428	−1.59265
CLEC2B	0.011826	−1.34674	NDUFB2	0.002603	−1.07679	SUCLA2	0.007537	−1.2347
CLEC4A	0.007489	−1.02954	NOC3L	0.002559	−1.35069	SUZ12	0.003601	−1.05487
CNIH4	0.010066	−1.14621	NRG1	0.010622	−1.09154	SYNCRIP	0.014028	−1.17322
COMMD8	0.007995	−1.55772	NSA2	0.003472	−1.06913	TAF7	0.007732	−1.14536
COPS2	0.002136	−2.01753	NUCB2	0.007942	−1.08371	TAX1BP1	0.002693	−1.06852
COPS4	0.001768	−1.43139	NUP58	0.009068	−1.06209	TBC1D15	0.006449	−1.1647
COX7A2	0.010036	−1.07453	NXT2	0.004281	−1.2521	TFEC	0.008791	−1.42258
COX7C	0.01057	−1.16601	OXR1	0.006095	−1.50406	THAP12	0.014428	−1.07614
CSNK1G3	0.011542	−1.01867	PDCD10	0.005711	−1.50133	TMCO1	0.002086	−1.5828
CSTA	0.007942	−1.73005	PEX2	0.003428	−1.2965	TMEM126B	0.007907	−1.20502
CYCS	0.009109	−1.0075	PFDN5	0.005586	−1.41994	TMEM135	0.010003	−1.11086
CYP1B1	0.011708	−1.11298	PHIP	0.010089	−1.3841	TMF1	0.009224	−1.07832
DBI	0.01023	−1.30864	PIGK	0.002056	−1.37603	TMX1	0.004423	−1.38867
DCUN1D1	0.01051	−1.25808	PIK3R1	0.002336	−1.03532	TNFAIP6	0.015404	−1.36049
DDX50	0.002056	−1.12659	PMAIP1	0.007907	−1.09809	TNFSF10	0.002082	−1.0818
DDX60	0.014028	−1.05148	PNRC2	0.009011	−1.07693	TRAT1	0.004006	−1.52595
DNAJA1	0.002647	−1.2838	POLR2K	0.009028	−1.13872	TRIM23	0.006705	−1.24923
DNAJC15	0.003366	−1.23698	POT1	0.005214	−1.03065	TTC33	0.010622	−1.07746
DPM1	0.009109	−1.14624	PPA2	0.001203	−1.26725	TWF1	0.012556	−1.19069
DYNLT3	0.003366	−1.48072	PPIG	0.003428	−1.09525	TXNDC9	0.003068	−1.4978
EIF3E	0.001992	−1.85498	PRKACB	0.002209	−1.44721	UCHL3	0.002306	−1.044
EMC2	0.014656	−1.0368	PRPF18	0.009109	−1.00778	UFL1	0.002284	−1.19304
ERGIC2	0.007784	−1.02373	PSMA2	0.002412	−1.60226	UQCRB	0.015198	−1.24802
EVI2A	0.002664	−2.28923	PSMA3	0.003815	−1.07933	UQCRH	0.001768	−1.36602
FAM35A	0.009392	−1.30097	PSMA4	0.004258	−1.45532	UQCRQ	0.004213	−1.58026
FPGT	0.014181	−1.06812	PSMC6	0.006492	−1.78049	USP1	0.002136	−1.13526
GALNT1	0.00292	−1.02446	PSMD10	0.007084	−1.0229	USP16	0.006337	−1.11092
GLRX	0.00396	−1.25846	PTP4A1	0.007236	−1.0124	VAMP7	0.001992	−1.28107
GMFB	0.010692	−1.10799	PTPN4	0.001629	−1.07738	ZBED5	0.006728	−1.21001
GNAI3	0.002965	−1.05599	PYROXD1	0.005212	−1.3728	ZC3H15	0.001992	−1.18085
GPR65	0.004174	−1.6033	RB1CC1	0.003366	−1.49063	ZCCHC10	0.011199	−1.30082
GTF2B	0.002693	−1.21	RBM39	0.015482	−1.0927	ZNF22	0.002782	−1.20885
GTF2H5	0.002694	−1.2895	RCN2	0.002653	−1.21558	ZNF267	0.006492	−1.57868
GZMA	0.007687	−1.12829	RDX	0.006646	−1.01147	ZNF292	0.003997	−1.44021
HAT1	0.004271	−1.79111	RPA3	0.002693	−1.14171	ZNF654	0.012597	−1.11143
HINT1	0.005014	−1.32867	RPAP3	0.010622	−1.05527	ZNF83	0.01493	−1.20098
HLTF	0.005211	−1.17621	RPL10	0.003134	−1.17675	ZNHIT3	0.003453	−1.20255
HMGB1	0.002744	−1.06703	RPL17	0.0049	−1.73562	ZZZ3	0.010504	−1.08037
HNMT	0.008262	−1.22766	RPL21	0.007635	−1.24714
HPR	0.011008	−1.01855	RPL27	0.002086	−1.13051

Table 3. Overlapping gene list (co-genes) of dif-miRNAs target genes and DEGs in VTE patients

Dif-miRNAs	Co-genes
hsa-miR-20a-3p	TLN1
hsa-miR-874	IMPA1, TTC33, NDUFA5, RPS23, TRAT1, RPAP3, STX7, MBNL1, TMF1, HNMT, RPS24, PMAIP1, HAT1, SEC62, TNFSF10, RPS27A, IFIT1, TMCO1
hsa-miR-522-3p	ATP5F1, DNAJC15, ANKRD49, UFL1, ATP6V1C1, RDX, GTF2H5, UQCRQ, PTPN4, RB1CC1, DPM1, MRPL13, RPL9, NAB1, IMPA1, PIK3R1, TMEM135, VAMP7, TTC33, HINT1, NDUFA5, HMGB1, MBNL2, GNAI3, SH2D1A, ATAD2B, CHMP5, TRAT1, RPAP3, STX7, OXR1, CASP3, PEX2, CAPZA1, MRPL3, LSM5, RPS15A, DCUN1D1, MBNL1, LRRC40, IL6ST, TXNDC9, TMX1, PTP4A1, SAMD9, CEP57, TMF1, CYCS, EVI2A, NOC3L, PYROXD1, COMMD8, MYBL1, EMC2, MS4A4A, SYNCRIP, CCDC91, SUZ12, RPA3, PPA2, RBM39, NXT2, COX7C, ZC3H15, RSL24D1, CAPZA2, RPS27A, PPIG, SMC4, C12orf29, ATG5, DNAJA1, CCNC, ZNF292, PSMA4, MCTS1, PHIP, PNRC2, RWDD1, TMCO1, ZNF654, ATP6V1D, ZZZ3, NRG1
hsa-miR-193a	ATP5F1, MRPL3, GMFB, NRG1, CEP57
hsa-miR-134	ATP5F1, ANKRD49, ATP6V1C1, RDX, LAMTOR3, PTPN4, NAB1, TBC1D15, PIK3R1, TMEM135, RCN2, NDUFA5, HMGB1, SH2D1A, ATAD2B, NDUFA4, CAPZA1, MRPL3, POLR2K, RPS15A, DCUN1D1, MBNL1, LRRC40, IL6ST, SAMD9, CEP57, TMF1, SAR1B, CYCS, HNMT, RPS24, CD86, GTF2B, CNIH4, GLRX, SEC62, GALNT1, CAPZA2, PPIG, MTHFD2, ATG5, PSMA4, FAM35A, IFIT1, RWDD1, NRG1
hsa-miR-483-3p	UQCRQ, NRG1, RPS24, ZNF292

Figure 1. Interaction network of dif-miRNAs and their co-gene targets in VTE patients

Table 4. Gene ontology (GO) function enrichment analysis of co-genes in VTE patients

Category	Term	P Value	Count	Genes
BP	translation	0.005175078	6	MRPL13, MRPL3, RSL24D1, RPS27A, RPS23, RPS24
BP	negative regulation of apoptotic process	0.04424408	5	CASP3, ATG5, DNAJA1, PIK3R1, TMF1
CC	nucleolus	1.15E-04	13	TMX1, ZC3H15, NOC3L, GTF2H5, GTF2B, SUZ12, RPL9, ZZZ3, RSL24D1, RPS23, RPS27A, RCN2, OXR1
CC	extracellular exosome	0.01487892	22	TLN1, LAMTOR3, STX7, IMPA1, GNAI3, CHMP5, IL6ST, CAPZA2, RDX, ATP6V1D, PPA2, PHIP, ATP6V1C1, TBC1D15, CD86, TNFSF10, HNMT, PTP4A1, VAMP7, DNAJA1, RPS27A, GLRX
MF	structural constituent of ribosome	9.78E-04	7	MRPL13, MRPL3, RPL9, RSL24D1, RPS27A, RPS23, RPS24
MF	poly(A) RNA binding	0.006437021	12	HMGB1, MRPL3, PPIG, ZC3H15, NOC3L, SYNCRIP, MBNL2, RDX, MBNL1, RBM39, RPS27A, RPS23

Abbreviation:BP, biological process; CC, cellular component; MF, molecular function.

Table 5. KEGG enrichment analysis of in VTE patients

Category	Term	P Value	Count	Genes
KEGG_PATHWAY	cfa03010:Ribosome	9.17E-05	8	MRPL13, MRPL3, RPL9, RPS15A, RSL24D1, RPS27A, RPS23, RPS24
KEGG_PATHWAY	cfa00190:Oxidative phosphorylation	0.003555	6	ATP6V1C1, NDUFA4, NDUFA5, UQCRQ, ATP6V1D, PPA2
KEGG_PATHWAY	cfa05012:Parkinson’s disease	0.004271	6	NDUFA4, NDUFA5, CASP3, GNAI3, CYCS, UQCRQ
KEGG_PATHWAY	cfa04932:nonalcoholic fatty liver disease (NAFLD)	0.004943	6	NDUFA4, NDUFA5, CASP3, CYCS, UQCRQ, PIK3R1
KEGG_PATHWAY	cfa05016:Huntington’s disease	0.014098	6	NDUFA4, NDUFA5, CASP3, POLR2K, CYCS, UQCRQ
KEGG_PATHWAY	cfa05010:Alzheimer’s disease	0.03951	5	NDUFA4, NDUFA5, CASP3, CYCS, UQCRQ

Figure 2. Predicted regulation on biological process (BP) of Co-genes by Dif-miRNAs in VTE patients

Table 6. Top ten co-genes genes (hub genes) with highest connectivities

Rank	Name	Score	Description
1	RPS27A	24	ribosomal protein S27a
2	CYCS	17	cytochrome c, somatic
3	MRPL13	16	mitochondrial ribosomal protein L13
4	RPL9	15	ribosomal protein L9
4	RPS15A	15	ribosomal protein S15a
6	RPS24	14	ribosomal protein S24
7	RPS23	13	ribosomal protein S23
7	PSMA4	13	proteasome 20S subunit alpha 4
9	HINT1	12	histidine triad nucleotide binding protein 1
9	NDUFA4	12	NDUFA4 mitochondrial complex associated

Figure 3. STRING protein–protein interaction analysis of co-genes

Figure 4. Predicted KEGG pathways involving top 10 hub genes regulated by dif-miRNAs in peripheral blood of VTE patients

Figure 5. Age distribution in each dataset before and after preprocessing (a. before preprocessing b. after preprocessing)