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eISSN: 2374-6920

Proteomics & Bioinformatics

Research Article Volume 7 Issue 3

A computational approach to identify microRNA (miRNA) based biomarker of Pharmacovariant from the regulation of disease pathology

Harishchander Anandaram

Department of Bioinformatics, Sathyabama University, India

Correspondence: Harishchander Anandaram, Department of Bioinformatics, Sathyabama University, India

Received: March 22, 2018 | Published: May 15, 2018

Citation: Anandaram H. A computational approach to identify microRNA (miRNA) based biomarker of Pharmacovariant from the regulation of disease pathology. MOJ Proteomics Bioinform. 2018;7(3):152 ? 170. DOI: 10.15406/mojpb.2018.07.00227

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Abstract

In the post genomic era, identification of a potential miRNA in a computational approach for the significance of a discovery of systemic biomarker with respect to pharmacovarient studies to treat diseases is a challenging task to execute. The challenge was addressed by identifying the Pharmacovarient based associate genes from Verse and it was followed by identifying the associated miRNAs from PharmacomiR and finally the transcription factors(TFs) of associate target genes were identified from RegNetworks. In the next step, a miRNA based regulatory network was constructed on the basis of association between genes, miRNAs and TFs. Finally, the network was analyzed on the basis of statistical studies and miRNA based compatibility to identify a potential miRNA to be utilized as a biomarker of Pharmacovarient to treat diseases in future. In this article, the computational approach was used for the identification of a miRNA based systemic biomarker in association with the pharmacovaience of Psoriasis and in future this approach can also be used for other diseases.

Keywords: pharmacovarience; transcription factors; post genomic era; RegNetworks; miRNA; biomarker.

Introduction

Psoriasis is a disorder mediated by immune system by making certain faulty signals in the human body. It’s still a belief that psoriasis can be developed under the specified condition i.e. “when the immune system signals the body to accelerate the growth of skin cells. In case of psoriasis, the skin cells mature in 3-6days. Instead of being in shed, the cells in skin get pile up to cause the visible lesions. It was also found that the genes that cause psoriasis can determine the reaction of a person’s immune system. These genes can either cause psoriasis or other conditions which are immune-mediated like Type-I Diabetes or rheumatoid arthritis. Pathophysiology of psoriasis involves the understanding of the occurrence of prominent pathologies in the major components of skin i.e. the epidermis and the dermis. There are two well established hypotheses about the process that occurs in the development of the disease. The first hypothesis considers psoriasis as a disorder with excessive growth and reproduction of skin cells. Here, the problem is viewed as a fault of the epidermis and its keratinocytes. In second hypothesis, the disease is viewed as an immune-mediated disorder. Here, the excessive reproduction of skin cells is secondary to the factors produced by the immune system.1,2

Micro RNA is a family of non coding RNA (ncRNA) which was discovered in 1993, it consist of 19-25 nucleotides and regulates the expression of approximately 30% of protein-coding miRNAs in humans.3 Base pairing at the position of 2-8 nucleotides were relative to the 5′ end of the small RNA to be termed as the “seed” region and it appears to be important for target recognition.3 Maturation of miRNAs involves multiple steps and initially two intermediate forms of miRNAs, namely primary (pri-) and precursor (pre-) miRNAs, were produced sequentially. In this process, Drosha (RNase III enzyme) and the double-stranded RNA (dsRNA) binding protein Dgcr8 cleaves the pri-miRNAs to produce a hairpin-shaped pre-miRNAs that are recognized by Exportin5 and they are subsequently transported from the nucleus to cytoplasm. There is another RNase III enzyme called Dicer which cleaves the pre-miRNAs to release ~22-nt double-stranded RNA duplexes (namely miRNA/miRNA* duplexes) with ~2-nt 3’ overhangs.4 One strand of a RNA duplex is termed as a mature miRNA which is further loaded into an Argonaute protein in the RNA-induced silencing complex (RISC) to exert its regulatory function on the basis of its binding with the target transcripts.5

A unique miRNA can regulate the expression of hundreds of proteins and the expression of a specific protein may be controlled by several miRNAs.6 The sequence conservation of most miRNAs lies between the distantly related organisms to suggest the impact of a strong evolutionary pressure7 and they have been shown to participate in many fundamental life processes like development, differentiation, organogenesis, growth control and apoptosis. Accordingly, deregulation of miRNA expression has been shown to contribute to cancer, heart diseases, infectious diseases, inflammatory diseases and other medical conditions, making them potential targets for medical diagnosis and therapy.8 Initially, Lee had found lin-4 as a regulator of developmental timing in nematode Caenorhabditis elegans.9 After several years, Reinhart had discovered lethal-7 (let-7) gene in Caenorhabditis elegans.10 At present, 2500 miRNAs are in the human genome. Majority of miRNA are intragenic.11 Micro RNAs are initially transcribed as a part of an RNA stem-loop that in turn forms part of a several hundred nucleotides long miRNA precursor miRNA (pri-miRNA).12

Results

Text mining of Genes from Pharmacogenomics and clinical varients were analyzed along with the associated miRNAs from PharmacomiR and transcription factors from Regnetworks and the analysis of interaction resulted in the pairing of 101 genes with 576 miRNAs and 638 transcription factors and the results were given in Table 1. A regulatory network was constructed in Cytoscape and the properties of the network were analyzed in the Network Analyzer. Finally, the hub genes were identified from cytohubba and the miRNA based regulation was analyzed on the basis of seed pairing in miRmap and triplex miRNA along with the experimental evidences from the previous literature.

S. No. Genes (Varse) miRNAs (pharmacomiR) Transcription factor (RegNetworks)
1.         ABCB1 hsa-miR-222, hsa-miR-338-5p & hsa-miR-451 AR,CEBPA,CEBPB,EGR1,EGR2, ETS1,HAX1,HIF1A,JUN,NFKB1
RARA,RNF2,SP1,TFAP2A,TP53
& WT1
2.         CYP3A4 hsa-miR-221 SP1 & TFAP2A
3.         CTLA4 hsa-miR-200C, hsa-miR-101, hsa-miR-105, hsa-miR-155, hsa-miR-205, hsa-miR-380, hsa-miR-384, hsa-miR-429, hsa-miR-432, hsa-miR-449b, hsa-miR-451, hsa-miR-496, hsa-miR-516a-3p, hsa-miR-517a, hsa-miR-651 & hsa-miR-656 BPTF, STAT5A & STAT5B
4.         TNF hsa-miR-27a, hsa-miR-130a, hsa-miR-130b, hsa-miR-149, hsa-miR-187, hsa-miR-19a, hsa-miR-296-3p, hsa-miR-409-5p, hsa-miR-454 AHR, ARNT, ATF1, ATF2, CEBPB, CEBPD, CREB1, EBF1, EGR1, EGR4, ELK1, ETS1, ETV4, FOS, IKBKB, IRF5, JUN, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFE2L1, NFKB1, NFKB1, NFKB2, POU2F1, RELA, RELA, SMAD6, SMAD7, SP1, SP3, SPI1, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6, TBP, TFAP2A & TP53
hsa-miR-516a-5p, hsa-miR-516b, hsa-miR-519b-3p, hsa-miR-542-3p, hsa-miR-581, hsa-miR-592, hsa-miR-599, hsa-miR-654-3p, hsa-miR-770-5p, hsa-miR-875-3p, hsa-miR-875-5p & hsa-miR-939
5.         MTHFR hsa-miR-331-5p, hsa-miR-103, hsa-miR-107, hsa-miR-125a-3p, hsa-miR-138, hsa-miR-16, hsa-miR-195, hsa-miR-214, hsa-miR-22, hsa-miR-220b, hsa-miR-24, hsa-miR-424, hsa-miR-486-3p, hsa-miR-497, hsa-miR-516a-5p, hsa-miR-565, hsa-miR-642 & hsa-miR-646 AHR, ARNT, CUX1, E2F1, EP300, JUN, MAX, MXI1::CLEC5A, MYC, REST, SP1, SREBF1, SREBF2, TFAP2A, USF1, XBP1
& YY1
6.         VDR hsa-miR-451, hsa-miR-124 BACH2, CREBBP, CTCF, FOS, FOSB, FOSL1, GTF2B, HMGN3, HNF4A, HR, JUN, JUNB, JUND, KDM5A, LMO2, MAX, MED1, NCOA1, NCOA2, NCOA6,
hsa-miR-125b, hsa-miR-506 NR0B2, NR1H2, NRIP1, RXRA, RXRB, RXRG, SMAD3, SNW1, STAT1 & TRIM24
& hsa-miR-544
 
7.         CREBBP hsa-miR-27b AIRE, ALX1, AR, ATF1, ATF4, BCL3, BRCA1, CALCOCO1, CDX2, CEBPA, CEBPB, CEBPD, CITED1, CITED2, CNOT3, CREB1, CREB3, CREB3L1, CREB3L3, CREB3L4 & CREB5
8.         ABCC2 hsa-miR-155, hsa-miR-339-5p CEBPB, HNF4A,PPARG::RXRA, RXRA & TP53
9.         UGT1A8 hsa-miR-181a MYB & SRF
10.      UGT1A9 hsa-miR-181c CUX1, MYB & SRF
11.      NR1I2 hsa-miR-181d, hsa-miR-148a & hsa-miR-148a NCOA1, NCOA3, NCOR2, POU1F1, PPARGC1A, RXRA, RXRB & RXRG
12.      AKT1 hsa-miR-181b, hsa-miR-125b, hsa-miR-149*, hsa-miR-185, hsa-miR-409-3p, hsa-miR-451& hsa-miR-625 AR, BRCA1, CREB1, EGR1
EP300, ESR1, ESR2, EZH2
FOXO1, FOXO3, FOXO4
GATA1, GATA2, HIST2, H2BE, HTT, IKBKB, IKBKG, MDM4
NFKB1, NFKBIA, NFKBIB
NKX3-1, NR4A1, PATZ1
PHB2, PPARA, PPARG, PPARGC1B, RELA, SMAD2
SMAD3, SMAD4, SMAD7
SP1, STAT1, STAT5A, TP53, TRIB3, XBP1, YBX1 & YY1
13.      MAP2K1 hsa-miR-19a, hsa-miR-103, hsa-miR-107, hsa-miR-1271, hsa-miR-130a, hsa-miR-130b, hsa-miR-144, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-181a, hsa-miR-181c, hsa-miR-195, hsa-miR-301a ATF1, ATF2, ATF3, ATF4, ATF5
hsa-miR-335, hsa-miR-34a, ATF6, ATF7, CREB1, ELK1, EP300, MYC, POU3F2 & SP1
hsa-miR-34c, hsa-miR-34c-5p,
hsa-miR-411, hsa-miR-424, hsa-miR-449a, hsa-miR-497, hsa-miR-501-5p, hsa-miR-506, hsa-miR-516a-3p, hsa-miR-545, hsa-miR-575, hsa-miR-620, hsa-miR-889 & hsa-miR-96
14.      PIK3CA hsa-miR-19b, hsa-miR-10a, hsa-miR-10b, hsa-miR-124, hsa-miR-135a, hsa-miR-135b, hsa-miR-148a, hsa-miR-148b, hsa-miR-152, hsa-miR-155, hsa-miR-193a-5p, hsa-miR-19a, hsa-miR-19b, hsa-miR-203, hsa-miR-302a, hsa-miR-302b, hsa-miR-302c, hsa-miR-302d, hsa-miR-370, hsa-miR-372, hsa-miR-373, hsa-miR-422a, hsa-miR-490-5p, hsa-miR-506, hsa-miR-512-3p, hsa-miR-520a-3p, hsa-miR-520a-5p, hsa-miR-520b, hsa-miR-520d-3p, hsa-miR-520e, hsa-miR-525-5p, hsa-miR-561, hsa-miR-576-5p CTCF, ESR1, FOXI1, FOXO1, FOXO3, FOXO3B, FOXO4, PGR
& hsa-miR-942 & TP53
15.      BCL2 hsa-miR-301b, hsa-let-7a, hsa-miR-1, hsa-miR-103, hsa-miR-106a, hsa-miR-107, hsa-miR-125a-5p, hsa-miR-125b, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-143, hsa-miR-153, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-17, hsa-miR-181a, hsa-miR-181b, hsa-miR-181c AR, ATF1, BCLAF1, BRCA1, CEBPA, CREB1, CTCF, CUX1, DDIT3, EGR1, ETS1, GLI1, GLI2
hsa-miR-181d, hsa-miR-182, hsa-miR-192, hsa-miR-195, hsa-miR-204, hsa-miR-20a, hsa-miR-21, hsa-miR-211, hsa-miR-217, hsa-miR-23a, hsa-miR-23b, hsa-miR-296-5p, hsa-miR-29a, hsa-miR-29b MYB, MYBL1, MYC, NFKB1, NFKB2, NR4A1, PARP1, PML
hsa-miR-29c, hsa-miR-30a, hsa-miR-30b, hsa-miR-30c, hsa-miR-338-5p, hsa-miR-34a, hsa-miR-34b, hsa-miR-34b*, hsa-miR-34c, hsa-miR-34c-5p, hsa-miR-365, hsa-miR-424, hsa-miR-429, hsa-miR-448, hsa-miR-451, hsa-miR-495, hsa-miR-497, hsa-miR-503, hsa-miR-504, hsa-miR-519a, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-548b-5p, hsa-miR-548c-3p, hsa-miR-548c-5p, hsa-miR-548d-5p, hsa-miR-587, hsa-miR-630, hsa-miR-641, hsa-miR-646 & hsa-miR-96 PPARG, RARA, RARB, RARG
RELA, SF1, SP1, STAT3, STAT5A
TP53 & WT1
16.      SLC30A8 hsa-miR-454, hsa-miR-143,hsa-miR-183, hsa-miR-186, hsa-miR-194, hsa-miR-205, hsa-miR-25 CEBPB, FOXO3, FOXO3B & HNF1A
hsa-miR-298, hsa-miR-378, hsa-miR-422a, hsa-miR-501-3p, hsa-miR-502-3p, hsa-miR-543, hsa-miR-563, hsa-miR-577, hsa-miR-874
& hsa-miR-9
17.      CD3G hsa-miR-301a, hsa-miR-136, hsa-miR-28-5p, hsa-miR-33b & hsa-miR-619 JUN
18.      CD4 hsa-miR-130a, hsa-miR-181c CREB1, ETS1, ETS2 & MYB
hsa-miR-181d, hsa-miR-221
hsa-miR-222 & hsa-miR-765
19.      CHN1 hsa-miR-130b, hsa-miR-194, hsa-miR-205, hsa-miR-210, hsa-miR-224, hsa-miR-300, hsa-miR-30a, hsa-miR-30d, hsa-miR-30e, hsa-miR-335, hsa-miR-452, hsa-miR-494, hsa-miR-502-5p, hsa-miR-543, hsa-miR-570 & hsa-miR-802 CUX1, FOXO3, FOXO3B, FOXO4
GTF3C1, NKX6-1, POU3F1, POU3F2, SREBF1, SREBF2
SRY & TCF3
20.      ELK1 hsa-miR-24, hsa-miR-135a, hsa-miR-135b, hsa-miR-136, hsa-miR-150, hsa-miR-185, hsa-miR-205, hsa-miR-326, hsa-miR-330-5p, hsa-miR-34b, hsa-miR-34c-3p AR, ARNT, BRCA1, BRCA1, CEBPA, CEBPB, CREBBP, CUX1, EGR1, EP300, FOS, ID1, ID2, ID3, KLF4, MAX, MXI1::CLEC5A, MYB, MYC, NFKB1, NFYA, PIAS2, SP1, SRF, STAT1, STAT2, TFAP2A, TFAP2C & USF1
hsa-miR-361-3p, hsa-miR-495
hsa-miR-498, hsa-miR-539, hsa-miR-542-5p, hsa-miR-626, hsa-miR-660 & hsa-miR-873
21.      FYN hsa-miR-15b, hsa-miR-125a-3p, hsa-miR-1271, hsa-miR-183, hsa-miR-326, hsa-miR-330-5p, hsa-miR-369-3p, hsa-miR-370, hsa-miR-376a ALX1, BCL3, CREB1, CTNNB1
hsa-miR-376b, hsa-miR-380, hsa-miR-452, hsa-miR-486-3p, hsa-miR-489, hsa-miR-569, hsa-miR-583 EGR1, HLF, HNRNPK, KHDRBS1
hsa-miR-586, hsa-miR-604, hsa-miR-624, hsa-miR-639, hsa-miR-646, hsa-miR-889, hsa-miR-921 NFIL3, NFKB1, NKX2-2, NR3C1
hsa-miR-939, hsa-miR-944& hsa-miR-96 PAX5, RFX1, RREB1, SP1, STAT1
VSX2 & YTHDC1
22.      LAT hsa-miR-497, hsa-miR-216b, hsa-miR-296-3p, hsa-miR-376c, hsa-miR-574-3p, hsa-miR-602, hsa-miR-604, hsa-miR-608, hsa-miR-631 CTCF, PAX2, PPARG, TFAP4 & YY1
& hsa-miR-941
23.      LCK hsa-miR-424 & hsa-miR-202 ARNT, CTCF, EBF1, ELK1
ESR1, ESR2, ETS1, HNF4A
KHDRBS1, MIF, MYB, NFKBIA
NR3C1, RXRA, SP1, STAT1, STAT3, STAT5A, TAL1, TCF3 & USF1
24.      MAP2K4 hsa-miR-16, hsa-miR-124, hsa-miR-128, hsa-miR-128a, hsa-miR-128b AHR, ARID5B, ARNT, PAX5 &
hsa-miR-136, hsa-miR-137, hsa-miR-141, hsa-miR-15b, hsa-miR-16 YY1
hsa-miR-195, hsa-miR-200a, hsa-miR-218, hsa-miR-22, hsa-miR-24
hsa-miR-25, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, hsa-miR-30b, hsa-miR-30d, hsa-miR-30e, hsa-miR-32
hsa-miR-363, hsa-miR-367, has-miR-374a, hsa-miR-424, hsa-miR-487b, hsa-miR-497, hsa-miR-503, hsa-miR-505, hsa-miR-506, hsa-miR-580, hsa-miR-892a, hsa-miR-92, hsa-miR-92a, hsa-miR-92b & hsa-miR-938
25.      MAP3K1 hsa-miR-195, hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, CEBPB, EGR1, IKBKB, IKBKG
hsa-let-7f, hsa-let-7g, hsa-let-7i, NFKB1, RELA & SPI1
hsa-miR-1, hsa-miR-106a, hsa-miR-106b, hsa-miR-124, hsa-miR-129-3p
hsa-miR-129-5p, hsa-miR-136,
hsa-miR-137, hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-190, hsa-miR-192, hsa-miR-193a-3p, hsa-miR-193b, hsa-miR-19a, hsa-miR-19b, hsa-miR-200b, hsa-miR-200c, hsa-miR-203, hsa-miR-206, hsa-miR-20a, hsa-miR-20b, hsa-miR-21, hsa-miR-23a, hsa-miR-23b
hsa-miR-30a, hsa-miR-31, hsa-miR-340, hsa-miR-371-5p, hsa-miR-372
hsa-miR-411, hsa-miR-429, hsa-miR-433, hsa-miR-488, hsa-miR-495, hsa-miR-499-3p, hsa-miR-506
hsa-miR-517b, hsa-miR-519d,
hsa-miR-520d-5p, hsa-miR-524-5p,
hsa-miR-544, hsa-miR-548c-3p,
hsa-miR-557, hsa-miR-582-5p, hsa-miR-590-5p, hsa-miR-607, hsa-miR-613, hsa-miR-643, hsa-miR-892b, hsa-miR-9, hsa-miR-93 & hsa-miR-98
26.      PTPN7 hsa-miR-15a & hsa-miR-126 E2F1, EGR1, GATA1 & MXI1::CLEC5A
27.      RAC1 hsa-miR-214, hsa-miR-101, hsa-miR-122, hsa-miR-137, hsa-miR-142-3p, hsa-miR-144, hsa-miR-155, hsa-miR-182, hsa-miR-194 ABL1, E2F1, EIF2AK2, ELK1, GABPA, NFKB1, RELA, STAT1
hsa-miR-200c, hsa-miR-217 STAT3 & YY1
hsa-miR-299-5p, hsa-miR-300
hsa-miR-320, hsa-miR-361-5p
hsa-miR-369-3p, hsa-miR-374a
hsa-miR-429, hsa-miR-485-3p
hsa-miR-518f, hsa-miR-655
& hsa-miR-96
28.      RAF1 hsa-miR-22, hsa-miR-125b, hsa-miR-135a, hsa-miR-135b, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-195, hsa-miR-19a, hsa-miR-19b, hsa-miR-424, hsa-miR-497, hsa-miR-516a-3p, hsa-miR-516b, hsa-miR-634, hsa-miR-646, hsa-miR-649 & hsa-miR-7 AR, MYC, NR3C1, RB1, RBL2, RFXANK, TSC22D3 & YY1
29.      RELA hsa-miR-544, hsa-miR-124, hsa-miR-138, hsa-miR-22, hsa-miR-302a, hsa-miR-302b, hsa-miR-302c AATF, AES, AHR, AR, BRCA1, CEBPB, CEBPD, CREBBP, EGR1, EGR1, EP300, ESR1, FOS, FUS, GTF2B, HDAC1, HDAC2, HDAC3, HEXIM1, HMGA2, IKBKB, IKBKG, ING4, IRF1, IRF2, IRF3, JUN, KAT2B, MEN1, MYC, NCOA3, NCOR2, NFKB1, NFKB2, NFKB2, NFKBIA, NFKBIB, NKRF, NKX2-1, NR3C1, PARP1, PAX6, PDCD11, PGR, PIAS1, PIAS3, PML, POU2F1, PPARA, PPARD, REL, RELB, RFC1, RXRA, SIN3A, SIRT1, SNIP1, SP1, SRF, STAT1, STAT3, STAT6, TAF1, TAF11, TAF4B, TAF6, TBP, TP53, TP53BP1, TRIB3, TRIP4, TSC22D3 & TWIST1
hsa-miR-302d, hsa-miR-329, hsa-miR-362-3p, hsa-miR-371-5p, hsa-miR-373, hsa-miR-506, hsa-miR-512-3p, hsa-miR-520f, hsa-miR-569
hsa-miR-596, hsa-miR-7, hsa-miR-769-5p & hsa-miR-891b
30.      CLAR hsa-miR-302e, hsa-miR-324-3p, hsa-miR-361-3p, hsa-miR-450b-3p, hsa-miR-516a-5p, hsa-miR-627, hsa-miR-660 & hsa-miR-768-5p AR, E2F1, E2F4, GABPA, MYC
NFYA, NKX2-1, NR3C1, RREB1
SP1, TFAP2A, TFAP2C, USF1
VSX2 & YY1
31.      CAMK4 hsa-miR-302d, hsa-miR-106a, hsa-miR-129-5p, hsa-miR-17, hsa-miR-187, hsa-miR-191, hsa-miR-20a ATF4, BACH1, BACH2, CREBBP
hsa-miR-299-3p, hsa-miR-30a EP300, HDAC4, MAX, MEF2A
hsa-miR-30b, hsa-miR-30c, hsa-miR-33a & hsa-miR-33b, hsa-miR-34b, hsa-miR-34c-3p, hsa-miR-455-5p, hsa-miR-507, hsa-miR-511, hsa-miR-567, hsa-miR-586, hsa-miR-885-5p & hsa-miR-96 MYC, PPARG & RELA
32.      CA1KK1 hsa-miR-302b, hsa-miR-103, hsa-miR-107, hsa-miR-145, hsa-miR-221, hsa-miR-222, hsa-miR-361-3p, hsa-miR-515-5p, hsa-miR-574-5p, hsa-miR-596, hsa-miR-619, hsa-miR-631, hsa-miR-634, hsa-miR-671-5p, hsa-miR-769-5p, hsa-miR-921 & hsa-miR-943 ARNT, BACH1, BACH2, E2F1, MAX, MXI1::CLEC5A, MYC, NFYA, PAX6, PPARG, TFAP2A
TFAP2C & USF1
33.      EDN1 hsa-miR-302a, hsa-let-7b, hsa-let-7c, hsa-miR-1, hsa-miR-147, hsa-miR-155, hsa-miR-185, hsa-miR-199a-5p, hsa-miR-203, hsa-miR-206, hsa-miR-220c, hsa-miR-454, hsa-miR-517b, hsa-miR-574-5p, hsa-miR-613 AR, CEBPA, CREB1, E2F1, FOXJ2
hsa-miR-648, hsa-miR-892a FOXO1, HIF1A, HLF, JUN, MEF2A, NFIC, NFKB1, PPARA, PPARG, SMAD1, SMAD3, SMAD4, TCF3 & ZEB1
& hsa-miR-935
34.      GATA4 hsa-miR-302c, hsa-miR-1, hsa-miR-200b, hsa-miR-200c, hsa-miR-208b & hsa-miR-429 ATF1,ATF2, ATF3, ATF4, ATF5
ATF6,ATF7, CEBPA, CREB1, CUX1, EP300, FOS, FOSB, HAND2, JARID2, JUN, JUNB
JUND, MED1, MEF2C, NFATC4
NFKB1, NFKB2, NKX2-5
NR5A1, PIAS1, RELA, SRF, TBX5
USF1& ZFPM2
35.      GSK3B hsa-miR-181d, hsa-miR-199a-5p, hsa-miR-199b-5p, hsa-miR-224, hsa-miR-26a, hsa-miR-26b, hsa-miR-548a-5p, hsa-miR-548b-5p, hsa-miR-548c-5p, hsa-miR-548d-5p, hsa-miR-582-3p, hsa-miR-647 & hsa-miR-876-3p APC, AR, ARNT, ATF4, BCL3, CDX2, CEBPA, CEBPA, CREB1,
CREB3, CREB3L1, CREB3L3,
CREB3L4, CREB5, CREM, CSDA, CTNNB1, CUX1, E2F1, E2F1, FOXO1, GLI1, GLI2, GLI3, HNRNPD, HOXA9, IKBKG, MEIS1, MITF, MYC, MYOCD, NFAT5, NFATC1
NFATC2, NFATC3, NFATC4
NFKB1, NFYA, NFYB, NFYC
NKX2-2, NOTCH2, PAX5, POU2F1, PPARGC1A, SNAI1
SOX9, SPI1, STAT5A, TP53 &
YBX1
36.      HAND1 hsa-miR-520a-3p, hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f, hsa-let-7g, hsa-let-7i FHL2, FOXD1, FOXF2, HEY2, HEYL, HOXA9, MEIS1, MYOD1, POU3F1, RORA, TCF12 & TCF3
hsa-miR-196a, hsa-miR-196b, hsa-miR-25, hsa-miR-32, hsa-miR-335, hsa-miR-363, hsa-miR-367, hsa-miR-92, hsa-miR-92a, hsa-miR-98
37.      HAND2 hsa-miR-520e, hsa-miR-1, hsa-miR-128, hsa-miR-135b, hsa-miR-140-5p, hsa-miR-181a, hsa-miR-181b, hsa-miR-181c, hsa-miR-181d, hsa-miR-202, hsa-miR-206, hsa-miR-25 AHR, ARNT, BPTF, CENPB, COPS5, EP300, FOXD3, GATA4
hsa-miR-296-5p, hsa-miR-32, hsa-miR-363, hsa-miR-367, hsa-miR-519a, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-543, hsa-miR-566 HEY2, HEYL, NPM1, PHOX2A
hsa-miR-615-5p, hsa-miR-661, hsa-miR-767-3p, hsa-miR-876-3p, hsa-miR-92, hsa-miR-92a & hsa-miR-92b SRY, TCF3 & VSX2
38.      HDAC5 hsa-miR-373, hsa-miR-124, hsa-miR-128, hsa-miR-134, hsa-miR-30a, hsa-miR-30b, hsa-miR-506, hsa-miR-589, hsa-miR-629, hsa-miR-653, hsa-miR-765, hsa-miR-768-3p & hsa-miR-9 ANKRA2, BCL6, BCOR, CIITA,
HR, KLF4, MAX, MEF2A, MEF2C
MEF2D, NCOR1, NCOR2, NFKB2
NRIP1, PHB2, RFXANK, RUNX3
USF1 & ZBTB16
39.      HDAC9 hsa-miR-520c-3p, hsa-miR-124, hsa-miR-147, hsa-miR-182, hsa-miR-190b, hsa-miR-199b-5p, hsa-miR-19a, hsa-miR-26a, hsa-miR-26b, hsa-miR-27a, hsa-miR-27b, hsa-miR-299-5p, hsa-miR-302b, hsa-miR-302c, hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d, hsa-miR-30e, hsa-miR-32, hsa-miR-338-5p, hsa-miR-365, hsa-miR-377, hsa-miR-383, hsa-miR-409-5p,hsa-miR-452,hsa-miR-506,hsa-miR-514, hsa-miR-515-5p, hsa-miR-542-5p, hsa-miR-558, hsa-miR-768-3p, hsa-miR-891a & hsa-miR-96 KLF12, MEF2A, MEF2A, NCOR1
REST, SIN3A, SIN3B, USF1, ZBTB16 & ZEB1
40.      LIF hsa-miR-520b, hsa-miR-125a-5p, hsa-miR-125b, hsa-miR-1297, hsa-miR-181b, hsa-miR-181d, hsa-miR-199a, hsa-miR-199a-5p, hsa-miR-26a, hsa-miR-28-5p, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, hsa-miR-328, hsa-miR-331-3p, hsa-miR-346, hsa-miR-494, hsa-miR-504, hsa-miR-654-5p, hsa-miR-874 & hsa-miR-93 CTCF, EGR3, ETS1, ETS2, MZF1
NFKB1, PBX1, RREB1, STAT1
STAT2 & TBP
41.      MEF2C hsa-miR-520d-3p, hsa-miR-135a, hsa-miR-135b, hsa-miR-137, hsa-miR-153, hsa-miR-182, hsa-miR-183, hsa-miR-18a, hsa-miR-18b, hsa-miR-190, hsa-miR-190b, hsa-miR-194, hsa-miR-19a, hsa-miR-19b, hsa-miR-203, hsa-miR-21, hsa-miR-223, hsa-miR-23a, hsa-miR-23b, hsa-miR-27b, hsa-miR-302a, hsa-miR-302b, hsa-miR-302c, hsa-miR-302d, hsa-miR-330-3p, hsa-miR-331-5p, hsa-miR-33a, hsa-miR-340, hsa-miR-372, hsa-miR-421, hsa-miR-448, hsa-miR-450b-5p, hsa-miR-520a-3p, hsa-miR-520b, hsa-miR-520c-3p, hsa-miR-520d-3p, hsa-miR-520d-5p, hsa-miR-520e, hsa-miR-520f, hsa-miR-524-5p, hsa-miR-556-3p, hsa-miR-603, hsa-miR-621 & hsa-miR-656 ATF2, BPTF, CDC5L, CREB1, CUX1, EP300, ESR1, FOXD3, FOXI1, FOXJ2, GATA4, HDAC4
HDAC5, HLF, IRF1, KLF12, MEF2A, MEF2D, NCOA2,NKX2-2
NKX3-1,PAX6,PBX1,POU2F1, POU2F2,POU3F1,POU3F2,POU3F3
POU5F1,SMAD2,SP1,SP1,SPI1, STAT5A,STAT5B,TCF3,TEAD1
TFAP4,TGIF1,TWIST2 & VGLL2
42.      MYL2 hsa-miR-124, hsa-miR-490-5p HNF1A & MEF2A
hsa-miR-593 & hsa-miR-876-5p
43.      ACTA1 hsa-miR-506, hsa-let-7a,hsa-let-7b ABL1, E2F4, ELK1, HCLS1, MEF2A, NR3C2, REST, SRF, TBP
hsa-let-7c,hsa-let-7d,hsa-let-7e, hsa-let-7f, hsa-let-7g, hsa-let-7i, hsa-miR-122,hsa-miR-155,hsa-miR-21 TP53 & ZEB1
hsa-miR-220c,hsa-miR-569, hsa-miR-574-5p & hsa-miR-98
44.      PDPK1 hsa-miR-23a, hsa-miR-147, hsa-miR-181a, hsa-miR-181c, hsa-miR-214, hsa-miR-27a, hsa-miR-27b, hsa-miR-323-5p, hsa-miR-374b, hsa-miR-375, hsa-miR-382, hsa-miR-410, hsa-miR-486-3p, hsa-miR-499-3p, hsa-miR-504, hsa-miR-885-3p & hsa-miR-944 EGR1, EGR3, GABPA, PPARD
RXRA, RXRB, RXRG & SP1
45.      RPS6KB1 hsa-miR-23b, hsa-miR-103, hsa-miR-107, hsa-miR-124, hsa-miR-128, hsa-miR-129-5p, hsa-miR-130a E2F1, E2F2 & LMO2
hsa-miR-130b, hsa-miR-135a, hsa-miR-135b, hsa-miR-137, hsa-miR-142-5p, hsa-miR-145, hsa-miR-153
hsa-miR-155, hsa-miR-181a, hsa-miR-181b, hsa-miR-181c, hsa-miR-181d, hsa-miR-186, hsa-miR-200b
hsa-miR-200c, hsa-miR-218, hsa-miR-223, hsa-miR-27a, hsa-miR-27b, hsa-miR-301a, hsa-miR-301b
hsa-miR-340, hsa-miR-369-3p, hsa-miR-377, hsa-miR-429, hsa-miR-506, hsa-miR-507, hsa-miR-548c-3p, hsa-miR-557, hsa-miR-561, hsa-miR-568, hsa-miR-579, hsa-miR-590-3p, hsa-miR-605, hsa-miR-607, hsa-miR-641, hsa-miR-655, hsa-miR-7 & hsa-miR-944
46.      YWHAH hsa-miR-125b, hsa-miR-103, has-miR-107, hsa-miR-137, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-195, hsa-miR-25, hsa-miR-28-3p, hsa-miR-33, hsa-miR-33a, hsa-miR-33b, hsa-miR-361-5p, hsa-miR-365, hsa-miR-381, hsa-miR-421, hsa-miR-424, hsa-miR-490-5p, hsa-miR-497, hsa-miR-519d, hsa-miR-521, hsa-miR-523,hsa-miR-563, hsa-miR-576-5p,hsa-miR-583, hsa-miR-584, hsa-miR-586, hsa-miR-598, hsa-miR-652, hsa-miR-660, hsa-miR-708, hsa-miR-885-5p, hsa-miR-888, hsa-miR-95& hsa-miR-96 ABL1, ATF2, CREB1, CREBBP, E2F4, EGR3, ESR1, ESR2, ING1, JUN, MDM4, MED1, MEF2A, MYC, NCOA1, NCOA2, NCOA3, NR3C1, NRIP1, TFAP2A, THRA, TLX2, TNFAIP3, YY1 & ZFP36
47.      ADSS hsa-miR-125a-5p, hsa-miR-1, hsa-miR-16, hsa-miR-182, hsa-miR-19a CTCF, EGR1, EGR2, EGR3
hsa-miR-19b, hsa-miR-206, hsa-miR-28-3p, hsa-miR-383, hsa-miR-503, hsa-miR-514, hsa-miR-548a-3p KLF12, SP1, TFAP2A & TFAP2C
hsa-miR-548a-5p, hsa-miR-548b-5p
hsa-miR-548c-5p, hsa-miR-548d-5p
hsa-miR-561, hsa-miR-609, hsa-miR-642, hsa-miR-922, hsa-miR-923 & hsa-miR-96
48.      CDKN1A hsa-miR-590-3p, hsa-miR-449a, hsa-miR-449b, hsa-let-7a, hsa-let-7e, hsa-let-7f, hsa-miR-106a, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-130b, hsa-miR-132, hsa-miR-145, hsa-miR-146a, hsa-miR-146b-5p, hsa-miR-17, hsa-miR-17-5p,hsa-miR-182, hsa-miR-193a-5p,hsa-miR-20, hsa-miR-208a AR, ATF2, CDC5L, CEBPA, CEBPA, ESR1, ESR1, ETS1, FLI1, FOS, FOXC1, FOXD1, FOXF2, FOXJ2, HDAC11, HIF1A, HNF4A, JUN, PARP1, PPARG, RARA, RB1, RELB, SMAD1, SMAD2, SMAD3, SMAD4, SP1, SP3, SP4, SRF, STAT1, STAT3, TFAP2A, TP53, TP53, TP63, TP73, TSG101, WT1&XRCC6
hsa-miR-208b, hsa-miR-20a, hsa-miR-20b, hsa-miR-21, hsa-miR-212, hsa-miR-22, hsa-miR-224, hsa-miR-28-5p, hsa-miR-298, hsa-miR-299-5p, hsa-miR-301a, hsa-miR-301b
hsa-miR-302a, hsa-miR-345, hsa-miR-363, hsa-miR-370, hsa-miR-372, hsa-miR-423-3p,
hsa-miR-454, hsa-miR-503, hsa-miR-509-3-5p, hsa-miR-515-3p, hsa-miR-516a-3p, hsa-miR-519a, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-519d, hsa-miR-519e, hsa-miR-520a-3p, hsa-miR-520b, hsa-miR-520g, hsa-miR-520h, hsa-miR-572, hsa-miR-608, hsa-miR-639, hsa-miR-641, hsa-miR-654-3p, hsa-miR-657, hsa-miR-93, hsa-miR-939
hsa-miR-942 & hsa-miR-96
49.      GNAQ hsa-miR-381, hsa-miR-142-3p, hsa-miR-182, hsa-miR-423-5p, hsa-miR-491-3p, hsa-miR-574-3p, hsa-miR-581, hsa-miR-587, hsa-miR-642, hsa-miR-886-3p & hsa-miR-96 CTCF, CUX1, EGR1, MEF2A & PPARG
50.      MARCKS hsa-miR-300, hsa-miR-1, hsa-miR-128a, hsa-miR-128b, hsa-miR-138, hsa-miR-142-3p, hsa-miR-143, hsa-miR-144, hsa-miR-182, hsa-miR-200b, hsa-miR-200c, hsa-miR-205, AHR, ALX1, ARNT, HNF1A
hsa-miR-206, hsa-miR-21, hsa-miR-216a, hsa-miR-218, hsa-miR-222, MZF1, NFKB1, PAX6, POU2F1
hsa-miR-23a, hsa-miR-25, hsa-miR-27a, hsa-miR-27b, hsa-miR-300, hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d, hsa-miR-30e, hsa-miR-370, hsa-miR-429, hsa-miR-491-5p, hsa-miR-495, hsa-miR-499-5p, hsa-miR-561, hsa-miR-655, hsa-miR-770-5p & hsa-miR-876-3p TOB1 & YY1
51.      SP1 hsa-miR-153, hsa-miR-1, hsa-miR-105, hsa-miR-124, hsa-miR-128, hsa-miR-128a, hsa-miR-128b, hsa-miR-135a, hsa-miR-135b, hsa-miR-137, hsa-miR-138, hsa-miR-149, hsa-miR-150, hsa-miR-155, hsa-miR-203, hsa-miR-204, hsa-miR-206, hsa-miR-211, hsa-miR-216a, AATF, AHR, AR, ARNT, ATF7IP
hsa-miR-218, hsa-miR-22, hsa-miR-223, hsa-miR-24, hsa-miR-27a, BCL6, BCOR, BRCA1, CEBPA, CEBPB, E2F1, E2F2, E2F3, E2F4, EGR1, EGR1, EGR3, ELF1, EP300, ESR1, ESR2, ETS1, GABPA, GATA1, HCFC1, HDAC1, HDAC2, HIF1A, HMGA1, HNF4A, HTT, JUN, KLF10, KLF4, KLF6, MEF2A, MEF2C, MEF2D, MIS18BP1, MSX1, MYB, MYC, MYOD1, MYOG, NCOR1, NCOR2,
hsa-miR-27b, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, hsa-miR-300, hsa-miR-32, hsa-miR-320, NFYA, NFYB, NR2F1, NR5A1,
hsa-miR-324-5p, hsa-miR-335, PAX6, PER3, PML, POU2F1, POU2F1, PURA, RARA, RB1, RBBP4, RBL1, REL, RELA,
hsa-miR-361-5p, hsa-miR-362-3p, RREB1, RXRA, SMAD2, SMAD3
hsa-miR-374b, hsa-miR-375, hsa-miR-377, hsa-miR-381, hsa-miR-384, hsa-miR-410, hsa-miR-429 SMAD4, SOX10 & SOX8
hsa-miR-487a, hsa-miR-488, hsa-miR-495, hsa-miR-506, hsa-miR-539, hsa-miR-548a-5p, hsa-miR-548b-3p, hsa-miR-548b-5p, hsa-miR-548c-5p, hsa-miR-548d-5p, hsa-miR-570, hsa-miR-590-3p,
hsa-miR-603, hsa-miR-607, hsa-miR-613, hsa-miR-625 & hsa-miR-7
52.      SP3 hsa-miR-361-5p, hsa-miR-105, hsa-miR-124,hsa-miR-133a, hsa-miR-133b, hsa-miR-135a, hsa-miR-135b  E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, EGR1, EP300, ESR1
hsa-miR-145, hsa-miR-153, hsa-miR-155, hsa-miR-182, hsa-miR-223, hsa-miR-27a, hsa-miR-338-5p GABPA, HDAC1, HDAC2, MEF2A
hsa-miR-369-3p, hsa-miR-374a NFYA, PAX6, PBX1, PIAS1, RB1,
hsa-miR-374b, hsa-miR-410, hsa-miR-421, hsa-miR-448, hsa-miR-487a, hsa-miR-487b, hsa-miR-506 RBBP4 & SP1
hsa-miR-507, hsa-miR-520d-5p,
hsa-miR-522, hsa-miR-524-5p,
hsa-miR-548a-5p, hsa-miR-548b-5p
hsa-miR-548c-5p, hsa-miR-548d-5p
hsa-miR-568, hsa-miR-580, hsa-miR-590-3p, hsa-miR-634, hsa-miR-655, hsa-miR-889 & hsa-miR-96
53.      MAPK3 hsa-miR-429, hsa-miR-132, hsa-miR-212, hsa-miR-497 & hsa-miR-613 AR, BCL3, CEBPB, ELK1, ELK4, ESR1,ETS1,ETS2,ETV6, ETV7, FOS, GATA1, GATA4, GTF2I, HDAC4, HIF1A, HSF1, HSF4, JUN, JUND, MAX, MITF, MYC, NR3C1, PPARA, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD9, SNAI2, SP1, SPIB, SREBF1, SREBF2, STAT3, STAT5A, TAL1, TAL2, TCF3, TGIF1, TOP2B, TP53, UBTF, USF1, YY1 & ZNF7
54.      PRKCA hsa-miR-200b, hsa-miR-147, hsa-miR-183, hsa-miR-186, hsa-miR-200c, hsa-miR-203, hsa-miR-205, hsa-miR-25, hsa-miR-340, hsa-miR-362-5p, hsa-miR-495, hsa-miR-522 AR, BTG2, CREM, DDX5, DLX3, EDF1, EWSR1, HABP4, HAND1
hsa-miR-545, hsa-miR-548a-5p, hsa-miR-548b-5p, hsa-miR-548c-5p HAND2, HES1, HMGN1, HMGN2
hsa-miR-548d-5p, hsa-miR-590-3p MAX, MXI1::CLEC5A, MYOD1
hsa-miR-603, hsa-miR-9 & hsa-miR-15a NFATC1, NFKB1, PA2G4, PPARA
RARA, RARA, SP1, TFAP2A
TP53, TRIM29 & USF1
55.      FOS hsa-miR-340, hsa-miR-345-3p, hsa-miR-4771, hsa-miR-4765, hsa-miR-4749-5p, hsa-miR-4749-3p, hsa-miR-4742-5p, hsa-miR-4742-3p, hsa-miR-4732-5p, hsa-miR-4732-3p ATF1, ATF2, ATF7, BACH2, BATF, BCL3, CEBPB, CEBPG, COBRA1, CREB1, DDIT3, EGR1
hsa-miR-4692, hsa-miR-4659b-5p EGR2, ELK1, ELK3, ELK4, ESR1
hsa-miR-4659b-3p, hsa-miR-4657 ESR2, ETS1, ETS2, ETV4 & FLI1
hsa-miR-4645-5p, hsa-miR-4645-3p, hsa-miR-4534, hsa-miR-4533, hsa-miR-4522, hsa-miR-4521, hsa-miR-451a, hsa-miR-4519, hsa-miR-4518, hsa-miR-449c-5p, hsa-miR-449c-3p, hsa-miR-449b-5p, hsa-miR-449b-3p
hsa-miR-449a, hsa-miR-4484, hsa-miR-4479, hsa-miR-4457, hsa-miR-4425, hsa-miR-4419a, hsa-miR-4317, hsa-miR-4310, hsa-miR-4292
hsa-miR-4288, hsa-miR-4282, hsa-miR-4274, hsa-miR-4258, hsa-miR-4256, hsa-miR-383, hsa-miR-3690,
hsa-miR-3676-5p, hsa-miR-3676-3p, hsa-miR-3670, hsa-miR-3616-5p, hsa-miR-3616-3p, hsa-miR-3179, hsa-miR-3117-5p, hsa-miR-3117-3p, hsa-miR-30a-5p, hsa-miR-30a-3p, hsa-miR-301b, hsa-miR-29b-3p, hsa-miR-22-5p, hsa-miR-22-3p, hsa-miR-212-5p, hsa-miR-212-3p, hsa-miR-2116-5p, hsa-miR-2116-3p, hsa-miR-1827, hsa-miR-1470, hsa-miR-144-5p, hsa-miR-144-3p, hsa-miR-139-5p, hsa-miR-139-3p, hsa-miR-132-5p, hsa-miR-132-3p, hsa-miR-130b-5p, hsa-miR-130b-3p, hsa-miR-130a-5p, hsa-miR-130a-3p, hsa-miR-1302, hsa-miR-1283, hsa-miR-1269a, hsa-miR-125b-5p, hsa-miR-1255b-5p
hsa-miR-1252, hsa-miR-1249
hsa-miR-1227 & hsa-let-7a-5p
56.      JUN hsa-miR-324-3p, hsa-miR-139-5p, hsa-miR-141, hsa-miR-15a, hsa-miR-16, hsa-miR-200a, hsa-miR-200b, hsa-miR-200c, hsa-miR-216b, ABL1, AR, ATF1, ATF2, ATF3, ATF4,BATF,BCL3,BCL6,BRCA1,
hsa-miR-297, hsa-miR-30a, hsa-miR-340, hsa-miR-429, hsa-miR-495, hsa-miR-496, hsa-miR-517c, hsa-miR-520d-5p, hsa-miR-522, hsa-miR-524-5p, hsa-miR-612, hsa-miR-642, hsa-miR-758, hsa-miR-890, hsa-miR-889, hsa-miR-802, hsa-miR-766-5p, hsa-miR-766-3p, hsa-miR-661, hsa-miR-645, hsa-miR-614, hsa-miR-5706, hsa-miR-5684, hsa-miR-5587-5p, hsa-miR-5587-3p, hsa-miR-5586-5p, hsa-miR-5586-3p, hsa-miR-553, hsa-miR-548z, hsa-miR-548ao-3p, hsa-miR-548aj-3p, hsa-miR-544a, hsa-miR-539-3p, hsa-miR-520b, hsa-miR-519a-3p, hsa-miR-518e-5p, hsa-miR-518e-3p, hsa-miR-518a-5p, COBRA1,COPS5,CREB1,CREB5
hsa-miR-518a-3p, hsa-miR-516a-5p, CREBBP,DDIT3,E2F1,E2F4, EGR1,ELF3,EN1,EP300,ERG, ESR1, ESR2, ETS1, ETS2, FOS
hsa-miR-516a-3p, hsa-miR-5008-5p, FOSL1, FOSL2, GATA1, GATA2
hsa-miR-5008-3p, hsa-miR-5000-5p, hsa-miR-5000-3p, hsa-miR-487b, hsa-miR-487a, hsa-miR-4792, GATA3, GTF2B, GTF2F2, HCFC1
hsa-miR-4784, hsa-miR-4771, hsa-miR-4763-5p, hsa-miR-4763-3p, HDAC3, HHEX, HIF1A, HMGA1
hsa-miR-4732-5p, hsa-miR-4732-3p HOXA9, HOXC8, LEF1, MAF
hsa-miR-4716-5p, hsa-miR-4716-3p MAFB, MEF2A, MYBBP1A
hsa-miR-4696, hsa-miR-4692 MYC, MYOD1, NCOA1, NCOA2
hsa-miR-4687-5p, hsa-miR-4687-3p NCOA3, NFE2L1, NFE2L2, NFIC
hsa-miR-4683, hsa-miR-4665-5p NFYA, NR3C1, NR5A1, NRIP1
hsa-miR-4665-3p, hsa-miR-4659b-5p, hsa-miR-4659b-3p, hsa-miR-4640-5p, hsa-miR-4640-3p, hsa-miR-4534, hsa-miR-4521, hsa-miR-451a, hsa-miR-4519, hsa-miR-449c-5p, hsa-miR-449c-3p, hsa-miR-449b-5p, hsa-miR-449b-3p, hsa-miR-449a, hsa-miR-4457, hsa-miR-4434 & hsa-miR-4425 PGR, PIAS1, POU1F1, RARA, RARB, RARG, RB1, RBM39
REL, RELA, RUNX1, RUNX2
SKI, SMAD2, SMAD3, SMAD4
SMARCD1, SMARCD3, SNAPC5
SOX10, SOX8, SP1, SPI1, SPIB
SREBF1, SREBF2, STAT1, STAT2
STAT3, STAT4, STAT5A, STAT6
TAF1, TBP, TCF20, TCF4, TCF7
TCF7L1, TCF7L2, TGIF1, TRIP4
TSC22D3, VDR, HSF2 & JDP2
57.      MAPK8 hsa-miR-26a, hsa-miR-103, hsa-miR-107, hsa-miR-196b, hsa-miR-214, hsa-miR-548c-3p & hsa-miR-641 ATF2, COPS2, ELK1, ELK3, FOS HSF1, HSF4, JDP2, JUN, JUNB, JUND, IL8, MECOM, MYC, NFATC2, NFATC4, NR3C1, PAX2
PGR, PPARG, REL, SMAD2, SMAD3, SPIB, STAT3, TP53,TP73
& XRCC6
58.      SRC hsa-miR-1297, hsa-miR-137, hsa-miR-141, hsa-miR-144, hsa-miR-149, hsa-miR-153, hsa-miR-200a, hsa-miR-203, hsa-miR-220c, hsa-miR-31, hsa-miR-34a, hsa-miR-34c-5p, hsa-miR-449a, hsa-miR-449b, ABL1,AR, ARHGAP35,CTNNB1, DAB2, ESR1, ESR2, ETS1, ETS2, FOXO1, GTF2I, HCLS1, HNF1A,
hsa-miR-9, hsa-miR-940, hsa-miR-145 & hsa-miR-143 HNRNPK, IKBKB, KHDRBS1, MAX, MXI1::CLEC5A, MYC,
NFKBIA, NR1I2, PAX5, PGR,
PPARD, RXRA, SMARCB1, SMARCE1, SP1, SRF, STAT1,
STAT3, STAT5A, STAT5B,
STAT6, TFAP2A, THRA, TRIP6
WBP11 & YTHDC1
59.      GRB2 hsa-miR-26b, hsa-miR-124, hsa-miR-128a, hsa-miR-128b, hsa-miR-141, hsa-miR-153, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-182, hsa-miR-195, hsa-miR-200a ABL1, DAB2, DTX1, EGR1, ELK1,
hsa-miR-208b, hsa-miR-220c, hsa-miR-27a, hsa-miR-27b, hsa-miR-320, hsa-miR-329, hsa-miR-376c ESR1, FOXA2, FOXO1, FOXO3, FOXO3B, GABPA, HTT, KHDRBS1, KHDRBS2, MTA1
hsa-miR-424, hsa-miR-433, hsa-miR-497, hsa-miR-506, hsa-miR-520g, hsa-miR-520h, hsa-miR-532-3p, hsa-miR-941 & hsa-miR-96 MTA3, NPM1, PAX5 & TP63
60.      PIK3R1 hsa-miR-376c, hsa-miR-103, hsa-miR-107, hsa-miR-128, hsa-miR-132, hsa-miR-136, hsa-miR-150, hsa-miR-153, hsa-miR-155, hsa-miR-15a, hsa-miR-15b, hsa-miR-16 ABL1, CTCF, CTNNB1, EBF1, EGR1, EGR2, EGR3, ELK1, ESR1, GABPA, GATA3, GTF2H1, HNF1A, HOXA9, IRF1, KHDRBS1
hsa-miR-186, hsa-miR-195, hsa-miR-21, hsa-miR-212, hsa-miR-218 KLF12, MEF2A, MEIS1, NFE2L1
hsa-miR-221, hsa-miR-222, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, hsa-miR-361-5p, hsa-miR-424 NFIL3, NFKBIA, NFYA, NFYB
hsa-miR-448, hsa-miR-455-3p, hsa-miR-486-5p, hsa-miR-488, hsa-miR-495, hsa-miR-497, hsa-miR-503, hsa-miR-520a-5p, hsa-miR-525-5p, hsa-miR-532-3p, hsa-miR-542-3p, hsa-miR-545, hsa-miR-548a-3p, hsa-miR-548c-3p, hsa-miR-579, hsa-miR-590-5p, hsa-miR-603, hsa-miR-630, hsa-miR-655, hsa-miR-656, hsa-miR-767-5p, hsa-miR-891b NFYC, NR2F2, PBX1, PGR, POU3F1, POU3F2, RB1, SP1, USF1
hsa-miR-93 & hsa-miR-96 & WBP11
61.      ABCG2 hsa-miR-496, hsa-miR-192, hsa-mir-328, hsa-miR-328, hsa-miR-519c-3p FOS, JUN, MAX & USF1
hsa-miR-519d, hsa-miR-520a-3p
hsa-miR-520b, hsa-miR-520c-3p
hsa-miR-520d-3p, hsa-miR-520e
hsa-miR-520f, hsa-miR-520g & hsa-miR-520h
62.      SHC1 hsa-miR-186, hsa-miR-124, hsa-miR-1271, hsa-miR-127-5p, hsa-miR-140-3p, hsa-miR-140-5p, hsa-miR-198, hsa-miR-204, hsa-miR-211, hsa-miR-219, hsa-miR-219-5p ABL1, BCL3, ELK1, EP300, ESR1
hsa-miR-330-5p, hsa-miR-452, hsa-miR-506, hsa-miR-518e, hsa-miR-568, hsa-miR-572, hsa-miR-650, hsa-miR-9 & hsa-miR-96 ESR1, FOS, GABPA, JUN, NPM1
POU2F1, REL, RELA, SP1, STAT5A, STAT5B, TOPORS
& TP53
63.      SOS1 hsa-miR-495, hsa-miR-124, hsa-miR-132, hsa-miR-148b, hsa-miR-152, hsa-miR-155, hsa-miR-181a, hsa-miR-181b, hsa-miR-181d, hsa-miR-204, hsa-miR-211, hsa-miR-212, hsa-miR-217, hsa-miR-302c, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-30e, hsa-miR-506, hsa-miR-519a, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-520a-3p, hsa-miR-520b, hsa-miR-520c-3p, hsa-miR-520d-3p, hsa-miR-520e, hsa-miR-520f, hsa-miR-9 AR, BIN1, CTCF, EGR1, ESR1, NFIC, RARA, SP1, STAT3, TFAP2A, USF1, NFIC, RARA, SPRY1, SPRY2, CCND1, SPRY4
& hsa-miR-96 SPRY3, BCL2L1, CCND2, CCND3
MYC, SPRED1 & SPRED2
64.      CREB1 hsa-miR-653, hsa-miR-103, hsa-miR-124, hsa-miR-128a, hsa-miR-128b, hsa-miR-141, hsa-miR-181a ABL1, AHR, ARNT, ATF1, ATM, CEBPA, CEBPB, CIITA, CREBBP, CREM, EDF1, EGR1, EP300, FHL5, GLI2, GTF2F2, KAT5, KCNIP3, MYC, NFKB1, NFKB2,
hsa-miR-181b, hsa-miR-181c NR3C1, PDX1, REL, RELA, RELB,
hsa-miR-181d, hsa-miR-182, hsa-miR-200a, hsa-miR-223, hsa-miR-25, hsa-miR-27a, hsa-miR-27b, hsa-miR-32, hsa-miR-34b*, hsa-miR-363, hsa-miR-367, hsa-miR-433, hsa-miR-519b-3p, hsa-miR-526b SMARCA4, SMARCA5, SOX9,
hsa-miR-543, hsa-miR-552, hsa-miR-576-5p, hsa-miR-92a, hsa-miR-92b, hsa-miR-944 & hsa-miR-96 SRF, STAT3, THRA & TLX2
65.      PLCG1 hsa-miR-543, hsa-miR-101, hsa-miR-129, hsa-miR-129-5p, hsa-miR-149, hsa-miR-182, hsa-miR-200b, hsa-miR-218, hsa-miR-221, hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d ABL1, ATF2, CREB1, CTCF, E2F4
hsa-miR-30e, hsa-miR-34a, hsa-miR-429, hsa-miR-455-5p, hsa-miR-874 & hsa-miR-96 EEF1A1, EGR1, ESR1, GTF2H1
KHDRBS1, NFYA, SREBF1, SREBF2, TOPORS, USF1 & YY1
66.      CD247 hsa-miR-410, hsa-miR-214 & hsa-miR-346 EP300, FOS, JUN, SLA2, STAT5A
STAT5B & YY1
67.      ZAP70 hsa-miR-297, hsa-miR-331-3p, hsa-miR-34a, hsa-miR-34b, hsa-miR-34c-5p, hsa-miR-484, hsa-miR-629 ABL1, ATF6, CTCF, HNF4A, NFYA, NR2F1, NR2F2, SLA2, USF1 & XBP1
hsa-miR-885-3p & hsa-miR-939
68.      CSNK2A1 hsa-miR-520h, hsa-miR-125b AIP, APEX1, ARNT, ATF1, ATF2,
hsa-miR-141, hsa-miR-186, hsa-miR-200a, hsa-miR-216b & hsa-miR-221 BDP1, BRCA1, BRF1, CREBBP,
CREM, CTDP1, CTNNB1, CUX2,
DDIT3, EGR1, ETS1, FOS, GTF2A1, GTF2A1L, HCLS1, HDAC1, HDAC2, HDAC3, HES6,
HIF1A, HMGA1, HMGA2, HOXB7
HSF1, IFI16, IRF2, JUN, KLF1, MAX, MAZ, MEF2C, MYB, MYC,
MYCN, MYF5, NAP1L4, NFIC,
NFKB1, NFKBIA, NKX2-5, PGR,
PML, RELA, SHOX, SP1, SPIB,
SRF, SSRP1, SUB1, TCF7L2, TOPORS, TP53, UBTF, VDR, YY1
& ZHX1
69.      PTK2B hsa-miR-519c-3p, hsa-miR-19a, hsa-miR-205, hsa-miR-23a, hsa-miR-23b, hsa-miR-345, hsa-miR-515-5p CTCF, EGR1, EWSR1, GABPA
hsa-miR-647, hsa-miR-892b & hsa-miR-940 HNF4A, MYC, NFKB1, REST
SP1, SPI1, SRF, STAT3, TGFB1I1
& TP53
70.      CAMK2B hsa-miR-544 AHR, ARNT, ATF4, CTCF, E2F1
E2F2, E2F3, E2F4, E2F5, E2F6
E2F7, EGR1, EGR2, EGR3, ETS1
MEF2A, NFE2L1, PAX5, RORA
RREB1, RXRG, SP1, THRB, USF1
& XBP1
71.      HBXIP hsa-miR-192, hsa-miR-106a, hsa-miR-106b, hsa-miR-140-5p, hsa-miR-145, hsa-miR-16, hsa-miR-17, EEF1A1, GABPA, HNF1A, HNF4A MAF1, MAX, POU2F1, USF1 &
hsa-miR-18a, hsa-miR-18b, hsa-miR-20a, hsa-miR-20b, hsa-miR-370, hsa-miR-378, hsa-miR-492, hsa-miR-496, hsa-miR-515-3p, hsa-miR-519d, hsa-miR-519e, hsa-miR-520d-5p, hsa-miR-520g, hsa-miR-520h, hsa-miR-524-5p, hsa-miR-545, hsa-miR-590-3p, hsa-miR-606, hsa-miR-619, hsa-miR-631, hsa-miR-876-3p & hsa-miR-93 ZBTB16
72.      PPP3CA hsa-miR-328, hsa-let-7a, hsa-let-7b AHR, ARNT, CEBPB, CUX1, E2F1
hsa-let-7c, hsa-let-7e, hsa-let-7f, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, EGR1, FOXC1, FOXJ2, NFAT5, NFATC1, NFATC2, NFATC3, NFATC4, NFYA, PPARG & ZBTB6
hsa-let-7g, hsa-let-7i, hsa-miR-100, hsa-miR-106a, hsa-miR-106b, hsa-miR-142-3p, hsa-miR-145, hsa-miR-153, hsa-miR-17, hsa-miR-182, hsa-miR-20b, hsa-miR-21, hsa-miR-300
hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d, hsa-miR-30e, hsa-miR-31, hsa-miR-340, hsa-miR-34b, hsa-miR-372, hsa-miR-381, hsa-miR-410, hsa-miR-495, hsa-miR-499-5p, hsa-miR-501-3p,hsa-miR-502-3p, hsa-miR-519a, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-520d-3p, hsa-miR-520d-5p, hsa-miR-520e, hsa-miR-520g, hsa-miR-520h, hsa-miR-524-5p, hsa-miR-590-5p, hsa-miR-635, hsa-miR-93, hsa-miR-96
hsa-miR-98 & hsa-miR-99a
73.      NFATC1 hsa-miR-519c, hsa-miR-122, hsa-miR-124, hsa-miR-137, hsa-miR-143, hsa-miR-155, hsa-miR-506 & hsa-miR-611 AHR, ARNT, ATF2, CDC5L, EP300, FOXC1, FOXF2, FOXI1, FOXO1, FOXO3, FOXO3B, FOXO4, NFKB1, PAX5, REL, RELA, SPI1, SRF & USF1
74.      PPP3CB hsa-miR-371-5p, hsa-miR-101, hsa-miR-103, hsa-miR-107, hsa-miR-1297, hsa-miR-137, hsa-miR-140-3p CEBPA, CEBPB, DDIT3, EGR1,
hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-192, hsa-miR-195 EP300, NFAT5, NFATC1, NFATC2
hsa-miR-196b, hsa-miR-19b, hsa-miR-215, hsa-miR-222, hsa-miR-26a, hsa-miR-26b, hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b, hsa-miR-30e, hsa-miR-326, hsa-miR-424, hsa-miR-506, hsa-miR-559, hsa-miR-613, hsa-miR-645, hsa-miR-646, hsa-miR-660, hsa-miR-768-3p & hsa-miR-802 NFATC3, NFATC4, NR3C1 & PAX2
75.      RCAN1 hsa-miR-148a, hsa-let-7b, hsa-miR -103, hsa-miR-107, hsa-miR-124, hsa-miR-323-3p, hsa-miR-34a, hsa-miR-34c-5p & hsa-miR-506 ALX1, CREB1, EBF1, EGR1, IRF1
JUN, MAX, POU3F1, SP1, SPI1
STAT5A, TGIF1, USF1 & VSX2
76.      PPARG hsa-miR-196a, hsa-miR-128a, hsa-miR-130a, hsa-miR-130b, hsa-miR-138, hsa-miR-144, hsa-miR-20b, hsa-miR-27a, hsa-miR-27b, hsa-miR-301, hsa-miR-338-5p, hsa-miR-34a, hsa-miR-409-3p, hsa-miR-449a, hsa-miR-520b, hsa-miR-520c-3p, hsa-miR-520d-3p, hsa-miR-548a-5p, hsa-miR-548b-5p, hsa-miR-548c-5p, hsa-miR-548d-5p & hsa-miR-559 AR, BRD8, CEBPA, CEBPB, COPS5, CREB1, EDF1, EGR1, ESR1, ESR2, FOXO1, GATA1, HDAC3, HMGA1, MED1, NCOA1
NCOA2, NCOA3, NCOA4, NCOA6
NCOR1, NCOR2, NFE2L1, NFE2L2, NR0B1 & NR0B2
77.      NOS3 hsa-miR-10b BACH1, CTCF, EPAS1, ERG, ESR1, ESR2, ETS1, ETV4, GABPA
GATA1, GATA2, GATA3, JUN, NR2F2, RORA, SP1, SP1, SP3, SPI1, TAL1::GATA1, TFAP2A & TP53
78.      ADRB2 hsa-miR-142-3p, hsa-let-7a, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e CEBPA, CEBPB, CREB1, CUX1
hsa-let-7f, hsa-let-7g, hsa-let-7i, hsa-miR-155, hsa-miR-15a, hsa-miR-15b, hsa-miR-16, hsa-miR-195, hsa-miR-216b, hsa-miR-27a, hsa-miR-30a, hsa-miR-30a-5p, hsa-miR-30b ELK1, GATA1, HLF, NFIC, NFIL3
hsa-miR-30d, hsa-miR-30e, hsa-miR-424, hsa-miR-497, hsa-miR-556-3p, hsa-miR-605, hsa-miR-607 PBX1, RORA, STAT5A & TBP
hsa-miR-625, hsa-miR-634, hsa-miR-7, hsa-miR-888 & hsa-miR-98
79.      CORIN hsa-miR-873, hsa-miR-106a, hsa-miR-106b, hsa-miR-138, hsa-miR-148a, hsa-miR-152, hsa-miR-17, hsa-miR-20a, hsa-miR-20b, hsa-miR-302a, hsa-miR-302b, hsa-miR-302c, hsa-miR-302d, hsa-miR-373, hsa-miR-495, hsa-miR-520a-3p, hsa-miR-520b, hsa-miR-520c-3p CTCF
hsa-miR-520d-3p, hsa-miR-520e
hsa-miR-520f, hsa-miR-548a-3p, hsa-miR-561, hsa-miR-582-3p & hsa-miR-93
80.      GNAS hsa-miR-139-5p, hsa-let-7i, hsa-miR-105, hsa-miR-136, hsa-miR-138, hsa-miR-143, hsa-miR-155, hsa-miR-15b, hsa-miR-18a, hsa-miR-205, hsa-miR-218, hsa-miR-219-2-3p, hsa-miR-219-5p, hsa-miR-221, hsa-miR-223, hsa-miR-338-3p, hsa-miR-34b, hsa-miR-361-3p, hsa-miR-361-5p, hsa-miR-362-5p, hsa-miR-452, hsa-miR-453, hsa-miR-489, hsa-miR-494, hsa-miR-502-5p, hsa-miR-512-3p, hsa-miR-532-5p, hsa-miR-582-3p, hsa-miR-588, hsa-miR-596, hsa-miR-624, hsa-miR-625, hsa-miR-629, hsa-miR-630, hsa-miR-660, hsa-miR-876-3p & hsa-miR-943 CEBPA, CTCF, CUX1, E2F2, E2F4
HSF1, NFIL3, REST, TFAP2A, TFAP2C, USF1, VSX2 & YY1
81.      HSP90AA1 hsa-miR-133b AHR, AIP, AR, ARNT, ARNTL, CREB1, CTCF, EGR1, EIF2AK2, ESR1, HIF1A, HSF1, HSF2, IKBKB, IKBKG, MAX, MXI1::CLEC5A, MYC, MYOD1, NPAS2, NR2C2, NR3C1, NR3C2, PPARA, REST, RUNX1T1, SRF, STAT1, STAT3, TFAP2A, TFAP2C, TP53, USF1 & YY1
82.      GTF2A1 hsa-miR-9, hsa-miR-142-3p, hsa-miR-196a, hsa-miR-196b, hsa-miR-25, hsa-miR-32, hsa-miR-493 & hsa-miR-92a ARNT, BACH2, BCL3, ELK1, EP300, ESR1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, MAX, MXI1::CLEC5A, MYC, TAF1, TAF4, TBP, TBPL1, TRIP4 & USF1
83.      GTF2E1 hsa-miR-145, hsa-miR-124, hsa-miR-155, hsa-miR-200b, hsa-miR-200c, hsa-miR-221, hsa-miR-222, hsa-miR-300, hsa-miR-361-5p, hsa-miR-381, hsa-miR-429, hsa-miR-494, hsa-miR-506, hsa-miR-654-5p AES, E2F2, ERCC3, GTF2A1, GTF2A2, GTF2B, GTF2E2, GTF2F2, GTF2H1, GTF2H4, NFYA
& hsa-miR-944 SND1, SP1, TAF6, TBP, TCEA1, TRIM24, YY1 & ZEB1
84.      NR3C1 hsa-miR-384, hsa-miR-1, hsa-miR-124, hsa-miR-137, hsa-miR-141, hsa-miR-142-3p, hsa-miR-144, hsa-miR-181a, hsa-miR-181b, hsa-miR-181c, hsa-miR-181d, hsa-miR-182, hsa-miR-183, hsa-miR-18a, hsa-miR-18b, hsa-miR-200a, hsa-miR-200b, hsa-miR-200c, hsa-miR-204 AHR, AR, ARNT, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ATF7,
hsa-miR-206, hsa-miR-211, hsa-miR-22, hsa-miR-29a, hsa-miR-29b CEBPA, CEBPB, CREB1, CREBBP, CTCF, DDX54, E2F1, ECD, EGR1, EGR2, EGR3, ETS1, ETS2, HIF1A, JUN, KDM5A, MED14, NCOA1, NCOA2, NCOA6
hsa-miR-29c, hsa-miR-300, hsa-miR-30a, hsa-miR-30b, hsa-miR-320, hsa-miR-328, hsa-miR-340, hsa-miR-377, hsa-miR-381, hsa-miR-410, hsa-miR-429, hsa-miR-506, hsa-miR-515-5p, hsa-miR-518d-5p, hsa-miR-543, hsa-miR-548c-3p, hsa-miR-582-5p, hsa-miR-603 & hsa-miR-889 NCOR1, NCOR2, NFIA, NFIC, NFKB1, NFKB2,NR2F2 & NR2F6
85.      POLR2A hsa-miR-28-5p , hsa-miR-214, hsa-miR-542-5p & hsa-miR-873 ABL1, ALX1, ATF2, BARD1, BRCA1, CREB1, CREBBP, CTCF, CTDP1, ELL, ERCC6, FUS, GTF2B, HTATSF1, KLF12, MCM3,
MED21, NFIL3, NONO, NR3C1, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2L, POU2F1, PQBP1, SAFB, SND1, SP1, STAT1, STAT3, SUPT5H, TAF10, TBP, TCEA1, TCERG1, TFAP2A, UPF1, USF1
XAB2, XRCC5, YY1 & ZNF74
86.      GNB1 hsa-let-7g, hsa-miR-101, hsa-miR-139-5p, hsa-miR-218, hsa-miR-570 & hsa-miR-598 CREB1, EGR1, EGR2, EP300, HDAC5, MZF1, NFKB1, PATZ1
RELA, SP1 & VSX2
87.      RXRA hsa-miR-98, hsa-miR-124, hsa-miR-219-5p, hsa-miR-27a, hsa-miR-27b, hsa-miR-506, hsa-miR-626, hsa-miR-876-5p & hsa-miR-9 BCL3, BRD8, COPS2, CTNNB1, EDF1, EGR1, ESR1, FOXO1, FUS, GATA2, HMGA1, JMJD1C, MED1, MYC, MYOD1, NCOA1, NCOA2, NCOA3, NCOA4, NCOA6, NCOR2, NFKB1, NFKBIB, NPAS2, NR0B2, NR1H2, NR1H3, NR1H4, NR1I2, NR1I3, NR2F1, NR4A2, NRBF2, NRIP1, NSD1, PARP1, PAX8, POU2F1, PPARA, PPARD, PPARG, PPARGC1A, RARA, RARB, RARG & RELA
88.      SMARCD1 hsa-let-7c, hsa-miR-101, hsa-miR-127-5p, hsa-miR-133a, hsa-miR-133b, hsa-miR-141, hsa-miR-148a, ATF1, ATF2, ATF3, ATF4, ATF5
hsa-miR-148b, hsa-miR-150, hsa-miR-152, hsa-miR-191, hsa-miR-200a, hsa-miR-21, hsa-miR-223, hsa-miR-324-5p, hsa-miR-325, hsa-miR-369-5p, hsa-miR-370, hsa-miR-421, hsa-miR-490-3p, hsa-miR-515-5p, hsa-miR-552, hsa-miR-556-3p, hsa-miR-590-5p, hsa-miR-624, hsa-miR-7 & hsa-miR-940 ATF6, ATF7, CREB1, FOS, GATA1, JUN, MAX, MEIS1, MXI1::CLEC5A, MYC, NR3C1& REL
89.      SMARCE1 hsa-let-7a, hsa-miR-103, hsa-miR-107, hsa-miR-134, hsa-miR-135a, hsa-miR-135b, hsa-miR-22, hsa-miR-485-3p, hsa-miR-494, hsa-miR-512-5p, hsa-miR-520a-5p, hsa-miR-548a-5p, hsa-miR-548b-5p, hsa-miR-548c-3p, hsa-miR-548c-5p, hsa-miR-548d-5p, hsa-miR-555, hsa-miR-603, hsa-miR-609, hsa-miR-760 & hsa-miR-9 BAZ1B, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, ESR1, ESR2, IRF7, NCOA1, NCOA2, NCOA3, NR3C1, PAX5, RELB & SMAD1
90.      ANXA1 hsa-let-7i , hsa-miR-196a, hsa-miR-221, hsa-miR-222, hsa-miR-376c, hsa-miR-598 & hsa-miR-758 FOS, FOXL1, POU3F1 & TBP
91.      CAV1 hsa-let-7b, hsa-miR-106b, hsa-miR-124, hsa-miR-125a-3p, hsa-miR-203 ABL1, AR, ATF6, E2F1, E2F4, EGR1, ESR1, NFIC, PAX2, RFX1
hsa-miR-34b*, hsa-miR-34c-5p, hsa-miR-377, hsa-miR-409-3p, hsa-miR-494, hsa-miR-506, hsa-miR-548c-3p, hsa-miR-628-5p, hsa-miR-768-3p & hsa-miR-96 SP1, TFDP1, TP53 & XBP1
92.      LPL hsa-let-7e, hsa-miR-138, hsa-miR-155, hsa-miR-27a, hsa-miR-27b, hsa-miR-29a, hsa-miR-29b, hsa-miR-29c, hsa-miR-452, hsa-miR-588, hsa-miR-590-3p & hsa-miR-768-5p AR, ARNT, ASCC2, E2F1, E2F2,
E2F3, E2F4, E2F5, E2F6, E2F7, ESR1, POU2F1, POU2F2, POU3F1,
POU3F2, POU3F3, POU5F1, PPARA, PPARD, PPARG, RXRA,
RXRB & RXRG
93.      ACTB hsa-let-7d, hsa-miR-145, hsa-miR-216a, hsa-miR-221, hsa-miR-412, hsa-miR-582-3p, hsa-miR-647 & hsa-miR-648 ATF7IP, EEF1A1, EGR1, EGR3, ELK1, EP300, GABPA, HNF4A, HNRNPAB, NFKB1, NFKB2, NFYA, NFYB, NFYC, POLR2A, POU3F2, PPARG, REL, RELA, SMAD3, SMAD9, SMARCA4, SP1, SRF, STAT1, STAT3, TBP, TFAP2A & USF1
94.      ARID1A hsa-let-7f, hsa-miR-1, hsa-miR-101, hsa-miR-132, hsa-miR-144, hsa-miR-153, hsa-miR-185, hsa-miR-19a, hsa-miR-19b, hsa-miR-203, hsa-miR-212, hsa-miR-216, hsa-miR-216a, hsa-miR-221, hsa-miR-222, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d, hsa-miR-30e, hsa-miR-31 ARNT, CREB1, E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, FOXD3, FOXI1, GATA2, HNF4A, MAX, MLLT1, MXI1::CLEC5A, MYC, MZF1, PAX5, POU2F1, POU3F1, PPARG, SMARCA4, SOX9, SP1, SRF, TFAP2A, TFAP2C, TP53, USF1 & YY1
hsa-miR-324-5p, hsa-miR-340, hsa-miR-377, hsa-miR-485-3p, hsa-miR-486-5p, hsa-miR-548c-3p, hsa-miR-555, hsa-miR-568, hsa-miR-576-5p, hsa-miR-583, hsa-miR-625, hsa-miR-765, hsa-miR-876-3p, hsa-miR-885-3p & hsa-miR-9
95.      GTF2B hsa-miR-202, hsa-miR-1, hsa-miR-103, hsa-miR-107, hsa-miR-122, hsa-miR-187, hsa-miR-190, hsa-miR-190b, hsa-miR-199a-3p, hsa-miR-206, hsa-miR-214, hsa-miR-22 BCL3, CREBBP, EGR1, EP300, ESR1, ESRRA, FOXF2, GTF2E1, GTF2E2, GTF2F1, GTF2F2, HSF1, IKZF1, JUN, MAX, MCM2, MXI1::CLEC5A, MYC, NCOA1, NCOA3, NCOA4, NR2F1, NR5A1, POLR2A, POU2F1, POU2F2, POU3F2, REL, RELA, TAF9, TBP, TBPL1, TCEA2, THRA, USF1
hsa-miR-24, hsa-miR-26a, hsa-miR-26b, hsa-miR-338-3p, hsa-miR-384 & VDR
hsa-miR-488, hsa-miR-511, hsa-miR-520d-5p, hsa-miR-524-5p, hsa-miR-561, hsa-miR-582-5p, hsa-miR-607 & hsa-miR-633
96.      NF1 hsa-miR-30e , hsa-miR-103, has-miR-107, hsa-miR-10b, hsa-miR-125a-3p, hsa-miR-128, hsa-miR-135a, hsa-miR-135b, hsa-miR-137 ATF2, CREB1, CTCF, JUN, PATZ1
hsa-miR-144, hsa-miR-153, hsa-miR-15a, hsa-miR-15b, hsa-miR-16 PAX5, SP1, TBPL1 & TFAP2A
hsa-miR-182, hsa-miR-195, hsa-miR-19a, hsa-miR-19b, hsa-miR-200b, hsa-miR-200c, hsa-miR-217
hsa-miR-219-1-3p, hsa-miR-25, hsa-miR-27a, hsa-miR-27b, hsa-miR-30a, hsa-miR-30b, hsa-miR-30c, hsa-miR-30d, hsa-miR-30e, hsa-miR-338-5p, hsa-miR-340, hsa-miR-363, hsa-miR-369-3p, hsa-miR-370
hsa-miR-374a, hsa-miR-374b, hsa-miR-424, hsa-miR-448, hsa-miR-497, hsa-miR-519b-3p, hsa-miR-519c-3p, hsa-miR-543, hsa-miR-548d-3p, hsa-miR-552, hsa-miR-561
hsa-miR-571, hsa-miR-582-5p, hsa-miR-590-3p, hsa-miR-617, hsa-miR-625, hsa-miR-655, hsa-miR-876-5p, hsa-miR-944 & hsa-miR-96
97.      SMARCA4 hsa-miR-30c, hsa-miR-1, hsa-miR-101, hsa-miR-132, hsa-miR-139-5p, AHR, ARID1A, ARID1B, BRCA1, BRWD1, CEBPB, CHD4, CREB1, CTNNB1, E2F1, E2F4, EGR1, ESR1, ETS2, GABPA, HSF1, IKZF1, MYC, MZF1, NR3C1, PAX6, PBRM1, RB1, RELB, RFXAP, SMARCB1, SMARCC1, SMARCE1, STAT2, TMF1, TP53, YY1 & ZMYND11
hsa-miR-144, hsa-miR-155, hsa-miR-191, hsa-miR-206, hsa-miR-212, hsa-miR-221, hsa-miR-222, hsa-miR-296-5p, hsa-miR-301a, hsa-miR-30c, hsa-miR-452, hsa-miR-489, hsa-miR-495, hsa-miR-503, hsa-miR-508-5p, hsa-miR-512-3p, hsa-miR-517b, hsa-miR-568, hsa-miR-569, hsa-miR-574-3p, hsa-miR-582-5p, hsa-miR-613, hsa-miR-765 & hsa-miR-942
98.      SMARCB1 hsa-miR-30d, hsa-miR-1, hsa-miR-192, hsa-miR-206 & hsa-miR-300 CEBPB, E2F4, FOS, FOSB, FOSL1
HNF4A, JUN, JUNB, JUND, KLF1
MECP2, MYC, NR3C1, RB1, RELB
SMARCA4, TCF3, TFAP2A, TP53
& YEATS4
99.      SMARCC1 hsa-miR-30a, hsa-let-7a, hsa-let-7b, CEBPB, FOXC1, GABPA, HOXA9
hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f, hsa-let-7g, hsa-let-7i, hsa-miR-1, hsa-miR-124, hsa-miR-129-5p, hsa-miR-144, hsa-miR-153, hsa-miR-196a, hsa-miR-196b, hsa-miR-202, hsa-miR-206, hsa-miR-208b, hsa-miR-214, hsa-miR-23a, hsa-miR-23b, hsa-miR-29b, hsa-miR-29c, hsa-miR-330-3p, hsa-miR-339-3p, hsa-miR-488, hsa-miR-506, hsa-miR-548d-3p, hsa-miR-567, hsa-miR-610, hsa-miR-641 & hsa-miR-98 KLF1, MEIS1, NR3C1, RELB, SIN3A & SMARCA4
100.  SMARCC2 hsa-miR-30b, hsa-miR-28-5p, hsa-miR-30a, hsa-miR-30b, hsa-miR-30c, hsa-miR-30e, hsa-miR-519a, BAZ1B, CTCF, ESR1, GABPA
hsa-miR-519b-3p, hsa-miR-519c-3p, POLR2C & RELB
hsa-miR-519d, hsa-miR-568, hsa-miR-608, hsa-miR-708 & hsa-miR-938
101.  HRH1 hsa-miR-196b, hsa-miR-192, hsa-miR-324-5p, hsa-miR-518a-5p, hsa-miR-527, hsa-miR-583 FOS, HNF4A, JUN, MAX, NR2F1,
NR3C1, POU2F1,POU2F2,POU3F1,
POU3F2, POU3F3, POU5F1 &
TFAP2A

Table 1 Study animal information: ID, gender, age, and dates of data collection for each study animal

Construction of regulatory network (cytoscape)

The regulatory network was constructed with 101 genes, 576 miRNAs and 638 TFs. Network was initiated from the association of Pharmacogenomics and Clinical variants with the 1214 regulators (i.e. 638 TFs & 576 miRNAs) to interact with the 101 target genes in such a way to form 1316 nodes and 4174 edges.

Identification of hub genes in regulatory network in top-down approach (cytohubba)

The genes and their regulators (Micro RNAs & Transcription Factors) were subjected to the analysis in cytohubba by various global based statistical methods like Edge Percolated Component, Bottleneck, EcCentricity, Closeness, Radiality, Betweenness and Stress along with local based statistical methods like Maximal Clique Centrality, Density of Maximum Neighborhood Component, Maximum Neighborhood Component and degree to identify their connectivity. Among the various methods of analysis in top down approach only a global based statistics of EcCentricity method and the local based statistics of Maximal Clique Centrality along with Density of Maximum Neighborhood Component and Clustering coefficient methods in cytohubba resulted in obtaining a regulatory network of gene-miRNA-TFs in top-down approach. The details of regulatory network were given in Figure 1.

Figure1 Regulatory Network of SMARCA4, FOS, JUN & NF1 (Bottleneck method).

Implication of miRNAs in regulatory network

The implication of miRNAs in the regulatory network was analyzed on the basis of compatibility with respect to gene-miRNA seed pairing and gene-miRNA-miRNA triplex with respect to nature of binding and the details were given in Table 2.

S. No.

Genes

microRNA

No. of binding Sites (mIRmap)

Paired miRNA

Binding energy in Kcal/mol. (Triplex RNA)

Nature of binding (Triplex RNA)

1.

FOS

 

hsa-miR-139-5p

NIL

hsa-miR-543

-26.96

Canonical triplex

2.

JUN

NIL

NIL

NIL

NIL

3.

NF1

NIL

hsa-miR-590-3p

-22.46

Self complementary

4.

SMARCA4

NIL

hsa-miR-7

-21.16

Canonical triplex

Table 2 Implication of miRNA in regulatory network

Pathway analysis

The obtained genes from Varse data were subjected to pathway analysis in DAVID on the basis of P value and Benjamini statistic and the result is given in Table 3.

S. No. Pathway P Value Benjamini
1 T cell receptor signaling pathway 3.71E-27 7.08E-25
2 ErbB signaling pathway 1.03E-19 9.82E-18
3 Hepatitis B 4.00E-19 2.55E-17
4 Natural killer cell mediated cytotoxicity 4.20E-18 2.01E-16
5 Fc epsilon RI signaling pathway 2.93E-17 1.12E-15
6 Oxytocin signaling pathway 4.79E-17 1.53E-15
7 Neurotrophin signaling pathway 6.32E-17 3.00E-15
8 Osteoclast differentiation 3.45E-16 7.99E-15
9 Estrogen signaling pathway 7.95E-16 1.65E-14
10 B cell receptor signaling pathway 1.13E-15 2.12E-14
11 Focal adhesion 1.24E-14 2.14E-13
12 Choline metabolism in cancer 2.43E-14 3.87E-13
13 Prostate cancer 5.49E-14 8.06E-13
14 GnRH signaling pathway 9.23E-14 1.26E-12
15 MAPK signaling pathway 8.75E-13 1.11E-11
16 Proteoglycans in cancer 9.97E-13 1.19E-11
17 Prolactin signaling pathway 1.16E-12 1.30E-11
18 Thyroid hormone signaling pathway 2.84E-12 3.01E-11
19 VEGF signaling pathway 3.71E-12 3.73E-11
20 HIF-1 signaling pathway 5.14E-12 4.90E-11
21 Sphingolipid signaling pathway 6.09E-12 5.54E-11
22 Glioma 8.26E-12 7.17E-11
23 Pathways in cancer 1.01E-11 8.40E-11
24 Non-small cell lung cancer 3.19E-11 2.54E-10
25 Epstein-Barr virus infection 4.87E-11 3.72E-10
26 Ras signaling pathway 8.53E-11 6.26E-10
27 cAMP signaling pathway 9.40E-11 6.65E-10
28 Colorectal cancer 1.03E-10 7.02E-10
29 Chagas disease (American trypanosomiasis) 1.79E-10 1.18E-09
30 TNF signaling pathway 2.28E-10 1.45E-09
31 PI3K-Akt signaling pathway 2.84E-10 1.75E-09
32 Endometrial cancer 3.34E-10 1.99E-09
33 Cholinergic synapse 4.11E-10 2.38E-09
34 HTLV-I infection 6.66E-10 3.74E-09
35 Viral carcinogenesis 1.49E-09 8.13E-09
36 Fc gamma R-mediated phagocytosis 3.05E-09 1.62E-08
37 Renal cell carcinoma 3.33E-09 1.72E-08
38 Hepatitis C 3.97E-09 2.00E-08
39 Insulin signaling pathway 6.27E-09 3.07E-08
40 cGMP-PKG signaling pathway 6.57E-09 3.14E-08
41 Chronic myeloid leukemia 9.34E-09 4.35E-08
42 Influenza A 1.21E-08 5.50E-08
43 Acute myeloid leukemia 1.44E-08 6.39E-08
44 Chemokine signaling pathway 2.85E-08 1.24E-07
45 Toll-like receptor signaling pathway 3.70E-08 1.57E-07
46 Long-term potentiation 6.38E-08 2.65E-07
47 Tuberculosis 1.26E-07 5.11E-07
48 Melanogenesis 2.31E-07 9.18E-07
49 Dopaminergic synapse 2.63E-07 1.02E-06
50 FoxO signaling pathway 4.19E-07 1.60E-06
51 Insulin resistance 4.78E-07 1.79E-06
52 Pancreatic cancer 8.12E-07 2.98E-06
53 Rap1 signaling pathway 9.13E-07 3.29E-06
54 Amphetamine addiction 9.15E-07 3.24E-06
55 Adrenergic signaling in cardiomyocytes 9.94E-07 3.45E-06
56 Inflammatory mediator regulation of TRP channels 2.00E-06 6.81E-06
57 Wnt signaling pathway 4.58E-06 1.53E-05
58 mTOR signaling pathway 4.72E-06 1.55E-05
59 Alcoholism 6.59E-06 2.13E-05
60 Calcium signaling pathway 7.34E-06 2.34E-05
61 Gap junction 8.29E-06 2.60E-05
62 Platelet activation 2.06E-05 6.33E-05
63 Signaling pathways regulating pluripotency of stem cells 3.71E-05 1.13E-04
64 Non-alcoholic fatty liver disease (NAFLD) 6.73E-05 2.01E-04
65 Progesterone-mediated oocyte maturation 6.96E-05 2.04E-04
66 NF-kappa B signaling pathway 6.96E-05 2.04E-04
67 Toxoplasmosis 7.08E-05 2.05E-04
68 Circadian entrainment 1.22E-04 3.48E-04
69 Epithelial cell signaling in Helicobacter pylori infection 1.30E-04 3.65E-04
70 Glucagon signaling pathway 1.58E-04 4.38E-04
71 Adherens junction 1.80E-04 4.90E-04
72 Melanoma 1.80E-04 4.90E-04
73 Bacterial invasion of epithelial cells 3.02E-04 8.12E-04
74 Salmonella infection 4.23E-04 0.00112219
75 Leukocyte transendothelial migration 4.68E-04 0.00122285
76 MicroRNAs in cancer 4.98E-04 0.00128474
77 Long-term depression 6.82E-04 0.00173516
78 Apoptosis 7.93E-04 0.0019915
79 Regulation of actin cytoskeleton 8.25E-04 0.00204461
80 Central carbon metabolism in cancer 9.17E-04 0.00224429
81 Shigellosis 9.17E-04 0.00224429
82 Renin secretion 9.17E-04 0.00224429
83 Measles 9.57E-04 0.00231132
84 Aldosterone-regulated sodium reabsorption 0.001105 0.00263573
85 Bladder cancer 0.001336 0.00314759
86 Leishmaniasis 0.001468 0.00341608
87 Amoebiasis 0.001541 0.00354175
88 Pertussis 0.001875 0.00425941
89 Serotonergic synapse 0.001951 0.00437895
90 Glutamatergic synapse 0.002234 0.00495554
91 Type II diabetes mellitus 0.002411 0.00528499
92 Aldosterone synthesis and secretion 0.002634 0.00570882
93 Amyotrophic lateral sclerosis (ALS) 0.002803 0.00600498
94 AMPK signaling pathway 0.003142 0.00665578
95 Small cell lung cancer 0.00325 0.00681028
96 Dorso-ventral axis formation 0.003837 0.00794894
97 NOD-like receptor signaling pathway 0.003969 0.00813387
98 Regulation of lipolysis in adipocytes 0.004236 0.00858837
99 Thyroid cancer 0.004712 0.00945112
100 Herpes simplex infection 0.005813 0.01153254
101 Prion diseases 0.006801 0.01334673
102 Jak-STAT signaling pathway 0.007286 0.01415115
103 Bile secretion 0.008878 0.01705798
104 Oocyte meiosis 0.009287 0.01766261
105 Adipocytokine signaling pathway 0.009333 0.01757575
106 Vascular smooth muscle contraction 0.013248 0.02466453
107 Alzheimer's disease 0.014431 0.02659597
108 Endocrine and other factor-regulated calcium reabsorption 0.015978 0.02914871
109 Axon guidance 0.017142 0.03096358
110 TGF-beta signaling pathway 0.017343 0.03103337
111 Insulin secretion 0.018039 0.03197285
112 Cocaine addiction 0.020058 0.03519937
113 Tight junction 0.022995 0.03994476
114 Vibrio cholerae infection 0.02466 0.042429
115 Viral myocarditis 0.029784 0.05069879
116 Retrograde endocannabinoid signaling 0.031582 0.05325725
117 Inflammatory bowel disease (IBD) 0.039998 0.06666945
118 PPAR signaling pathway 0.044852 0.07400301
119 Transcriptional misregulation in cancer 0.048809 0.07975066
120 Thyroid hormone synthesis 0.049987 0.08096751
121 RIG-I-like receptor signaling pathway 0.049987 0.08096751
122 Gastric acid secretion 0.055396 0.08883728
123 African trypanosomiasis 0.057954 0.09211228
124 Antigen processing and presentation 0.061074 0.09619989
125 Primary immunodeficiency 0.061114 0.09549899
126 Huntington's disease 0.077264 0.11920531
127 Dilated cardiomyopathy 0.077477 0.11860761
128 Salivary secretion 0.081853 0.12419244
129 Rheumatoid arthritis 0.086334 0.12983754
130 Carbohydrate digestion and absorption 0.088331 0.1317769
131 ABC transporters 0.095613 0.14130501
132 Pancreatic secretion 0.09798 0.14365712
133 Basal transcription factors 0.099317 0.14451349

Table 3 Annotation of Kegg Pathways in direct approach.

Discussion

Combinatorial Analysis of miRNA based pharmacovarient association in regulatory network of Psoriasis indicate the fact that has-miR-139-5p was involved in the T cell receptor signaling pathway and contribute to the disease pathology of Psoriasis. In this article the significance of hsa-miR-139-5p was analysed for the pharmacologically associated genes of psoriasis and in the mere future the significance of miRNA association with Pharmacology will be analysed with respect to the associated genes of other diseases.

Materials and methods

PubMed

PubMed is an online search engine with open access facility to refer MEDLINE for identifying references and abstracts on topics in biomedical and life sciences. The United States National Library of Medicine (NLM) at the National Institutes of Health maintains the database as part of the Entrez system to retrieve information. Most of the records in PubMed contain links to the complete article, in PubMed Central.13 Information regarding the indexed journals in MEDLINE can be found in the Catalog of NLM.

Varse and pharmacomiR

Pharmaco-miR Verified Sets (VerSe) databas14 is generated from manual data mining of original research articles including the search terms ‘miRNA’ and ‘drug’ in the PubMed database.

Regnetwork

RegNetwork15 is a data base that contains five types (Transcription Factor-Transcription factor, Transcription Factor-Gene, Transcription Factor-microRNA, microRNA-Transcription Factor) of transcriptional and posttranscriptional regulatory relationships for human and mouse.

Cytoscape

Cytoscape16 software is used for network construction, visualization and analysis in bioinformatics with an open source platform for visualizing the interactions in molecular networks and integrating them with the profiles of gene expression. Additional features in cytoscape are available as plugins for network and molecular profiling.

Cytohubba

Cytohubba17 is a cytoscape plugin for performing the analyses of gene regulation & protein-protein interaction involved in the process of cellular pathways in the process of signal transduction. Cytohubba ranks the nodes of network by topological methods like Radiality, Betweenness, Closeness, Bottleneck, EcCentricity and etc.

miRmap

miRmap18 software addresses the challenges in post transcriptional repression of miRNAs in human genome by evolutionary, probabilistic thermodynamic and sequence-based features.

Triplex RNA

Triplex RNA19 is a database of cooperating micrRNAs with their mutual targets. In this database miRNA target prediction is based on the analysis of predicted miRNA triplex with molecular dynamics simulations and differential modeling procedures in mathematics.

DAVID

The database for Annotation, Visualization and Integrated discovery (DAVID) contain complete information about functional annotation of genes. The current version of DAVID20,21 is 6.8 and it provides a set of comprehensive tools for functional annotation of genes.

Methodology

(miRNA based association with pharmaco-clinical variants):

  1. Identify the disease associated genes from Varse.
  2.  Obtain the associated list of miRNAs and transcription factors for the disease associated genes from PharmacomiR & Regnetworks.
  3. Construct and analyze the network in Cytoscape.
  4. Identify the miRNA based hub genes and transcription factors from cytohubba.
  5. Identify the implication of miRNA in Regulatory network in miRmap & miRNA Triplex.
  6. Identify and analyze the gene associated pathways in DAVID.

Acknowledgements

None.

Conflict of interest

Author declares there is no conflict of interest.

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