Issue
ARNetMiT R Package: association rules based gene co-expression networks of miRNA targets
Corresponding Author(s) : M. í–zgür Cingiz
Cellular and Molecular Biology,
Vol. 63 No. 3: Issue 3
Abstract
miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.
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- Mamdani M, Williamson V, McMichael GO, Blevins T, et al. (2015). Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence. PloS ONE 10(9): e0137671.
- Liu B, Li J, Tsykin A, Liu L, et al. (2009). Exploring complex miRNA-mRNA interactions with Bayesian networks by splitting-averaging strategy. BMC Bioinformatics 10: 408.
- Lai X, Bhattacharya A, Schmitz U, Kunz M, et al. (2013). A systems' biology approach to study microRNA-mediated gene regulatory networks. BioMed Res Int 2013: 2013:703849.
- Gennarino VA, D'Angelo G, Dharmalingam G, Fernandez S, et al. (2012). Identification of microRNA-regulated gene networks by expression analysis of target genes. Genome Res 22(6): 1163-1172.
- Chawla S, Joseph GD and Pandey G (2004). On Local Pruning of Association Rules Using Directed Hypergraphs. Proc ICDE'04.
- Yang DH, Kang JH, Park YB, Oh HS, et al. (2013). Association rule mining and network analysis in oriental medicine. PLoS ONE 8(3): e59241.
- Martínez-Ballesteros M, Nepomuceno-Chamorro IA and Riquelme JC (2014). Discovering gene association networks by multi-objective evolutionary quantitative association rules. J Comput Syst Sci 80(1): 118-136.
- Belyi E, Giabbanelli PJ, Patel I, Harish N, et al. (2016). Combining association rule mining and network analysis for pharmacosurveillance. J Supercomput 72(5): 2014-2034.
- Jiang Q, Wang Y, Hao Y, Juan L, et al. (2009). miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37: D98-D104.
- Chou CH, Chang NW, Shrestha S, Hsu SD, et al. (2016). miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res 44(D1): D239-D247.
- Agrawal R and Ramakrishnan S (1994). Fast algorithms for mining association rules. Proc VLDB'94: 487-499.
- Zaki MJ (2000). Scalable algorithms for association mining. IEEE T Knowl Data En 12(3): 372-390.
- Borgelt C (2003). Efficient implementations of apriori and eclat. Proc FIMI'03.
- Castro MA, Wang X, Fletcher MN, Meyer KB, et al. (2012). RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations. Genome Biol 13(4): R29.
- Van den Bulcke T, Van Leemput K, Naudts B, van Remortel P, et al. (2006). SynTReN: a generator of synthetic gene expression
- n data for design and analysis of structure learning algorithms. BMC Bioinformatics 7(1): 43.
- Altay G (2012). Empirically determining the sample size for large-scale gene network inference algorithms. IET Syst Biol 6: 35-43.
- Giorgi FM, Del Fabbro C, Licausi F (2013). Comparative study of RNA-seq-and microarray-derived coexpression networks in Arabidopsis thaliana. Bioinformatics 29(6): 717-724.
- de Matos Simoes R, Dalleau S, Williamson KE and Emmert-Streib F (2015). Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead and Oligo gene expression data. BMC Syst Biol 9: 21.
- Altay G, Altay N, Neal D (2013). Global assessment of network inference algorithms based on available literature of gene/protein interactions. Turk J Biol 37(5): 547-555.
- Margolin AA, Nemenman I, Basso K, Wiggins C, et al. (2006). ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics 7(1): S7.
- Altay G and Emmert-Streib F (2010). Inferring the conservative causal core of gene regulatory networks. BMC Systems Biology 4(1): 132.
- Faith JJ, Hayete B, Thaden JT, Mogno I, et al. (2007). Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol 5(1): e8.
- Meyer PE, Kontos K, Lafitte F and Bontempi G (2007). Information-theoretic inference of large transcriptional regulatory networks. EURASIP J Bioinform Syst Biol 2007(1): 79879.
- Langfelder P and Horvath S (2008). WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1): 559.
- Meyer PE, Lafitte F and Bontempi G (2008). minet: AR/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics 9(1): 461.
- Shannon P, Markiel A, Ozier O, Baliga NS, et al. (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11): 2498-2504.
- Labhart P, Karmakar S, Salicru EM, Egan BS, et al. (2005). Identification of target genes in breast cancer cells directly regulated by the SRC-3/AIB1 coactivator. Proc Natl Acad Sci USA 102(5): 1339-1344.
- Nestal de Moraes G, Delbue D, Silva KL, Robaina MC, et al. (2015). FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance. Cell Signal 27(12): 2496-2505.
- Dawson SJ, Makretsov N, Blows FM, Driver KE, et al. (2010). BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer 103(5): 668-675.
- Dang CV (2012). MYC on the path to cancer. Cell 149(1): 22-35.
- Gerger A, Hofmann G, Langsenlehner U, Renner W, et al. (2009). Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk. Int J Colorectal Dis 24(2): 159-163.
- Wang Y, Kuramitsu Y, Ueno T, Suzuki N, et al. (2012). Glyoxalase I (GLO1) is up-regulated in pancreatic cancerous tissues compared with related non-cancerous tissues. Anticancer Res 32(8): 3219-3222.
- Hermann-Kleiter N, Klepsch V, Wallner S, Siegmund, K., et al. (2015). The nuclear orphan receptor NR2F6 is a central checkpoint for cancer immune surveillance. Cell rep 12(12): 2072-2085.
- Wu CH, Sahoo D, Arvanitis C, Bradon N, et al. (2008). Combined analysis of murine and human microarrays and ChIP analysis reveals genes associated with the ability of MYC to maintain tumorigenesis. PLoS Genet 4(6): e1000090.
- Grützmann R, Pilarsky C, Ammerpohl O, Lüttges J, et al. (2004). Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia 6(5): 611-622.
- Kobberup S, Nyeng P, Juhl K, Hutton J, et al. (2007). ETS"family genes in pancreatic development. Dev Dyn 236(11): 3100-3110.
- Wu X, Deng F, Li Y, Daniels G, et al. (2015). ACSL4 promotes prostate cancer growth, invasion and hormonal resistance. Oncotarget 6(42): 44849.
- Rüenauver K, Menon R, Svensson MA, Carlsson J, et al. (2014). Prognostic significance of YWHAZ expression in localized prostate cancer. Prostate Cancer Prostatic Dis 17(4): 310-314.
- He H, Dai F, Yu L, She X, et al. (2002). Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Gene Expression 10(5-1): 231-242.
References
Mamdani M, Williamson V, McMichael GO, Blevins T, et al. (2015). Integrating mRNA and miRNA Weighted Gene Co-Expression Networks with eQTLs in the Nucleus Accumbens of Subjects with Alcohol Dependence. PloS ONE 10(9): e0137671.
Liu B, Li J, Tsykin A, Liu L, et al. (2009). Exploring complex miRNA-mRNA interactions with Bayesian networks by splitting-averaging strategy. BMC Bioinformatics 10: 408.
Lai X, Bhattacharya A, Schmitz U, Kunz M, et al. (2013). A systems' biology approach to study microRNA-mediated gene regulatory networks. BioMed Res Int 2013: 2013:703849.
Gennarino VA, D'Angelo G, Dharmalingam G, Fernandez S, et al. (2012). Identification of microRNA-regulated gene networks by expression analysis of target genes. Genome Res 22(6): 1163-1172.
Chawla S, Joseph GD and Pandey G (2004). On Local Pruning of Association Rules Using Directed Hypergraphs. Proc ICDE'04.
Yang DH, Kang JH, Park YB, Oh HS, et al. (2013). Association rule mining and network analysis in oriental medicine. PLoS ONE 8(3): e59241.
Martínez-Ballesteros M, Nepomuceno-Chamorro IA and Riquelme JC (2014). Discovering gene association networks by multi-objective evolutionary quantitative association rules. J Comput Syst Sci 80(1): 118-136.
Belyi E, Giabbanelli PJ, Patel I, Harish N, et al. (2016). Combining association rule mining and network analysis for pharmacosurveillance. J Supercomput 72(5): 2014-2034.
Jiang Q, Wang Y, Hao Y, Juan L, et al. (2009). miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37: D98-D104.
Chou CH, Chang NW, Shrestha S, Hsu SD, et al. (2016). miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res 44(D1): D239-D247.
Agrawal R and Ramakrishnan S (1994). Fast algorithms for mining association rules. Proc VLDB'94: 487-499.
Zaki MJ (2000). Scalable algorithms for association mining. IEEE T Knowl Data En 12(3): 372-390.
Borgelt C (2003). Efficient implementations of apriori and eclat. Proc FIMI'03.
Castro MA, Wang X, Fletcher MN, Meyer KB, et al. (2012). RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations. Genome Biol 13(4): R29.
Van den Bulcke T, Van Leemput K, Naudts B, van Remortel P, et al. (2006). SynTReN: a generator of synthetic gene expression
n data for design and analysis of structure learning algorithms. BMC Bioinformatics 7(1): 43.
Altay G (2012). Empirically determining the sample size for large-scale gene network inference algorithms. IET Syst Biol 6: 35-43.
Giorgi FM, Del Fabbro C, Licausi F (2013). Comparative study of RNA-seq-and microarray-derived coexpression networks in Arabidopsis thaliana. Bioinformatics 29(6): 717-724.
de Matos Simoes R, Dalleau S, Williamson KE and Emmert-Streib F (2015). Urothelial cancer gene regulatory networks inferred from large-scale RNAseq, Bead and Oligo gene expression data. BMC Syst Biol 9: 21.
Altay G, Altay N, Neal D (2013). Global assessment of network inference algorithms based on available literature of gene/protein interactions. Turk J Biol 37(5): 547-555.
Margolin AA, Nemenman I, Basso K, Wiggins C, et al. (2006). ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics 7(1): S7.
Altay G and Emmert-Streib F (2010). Inferring the conservative causal core of gene regulatory networks. BMC Systems Biology 4(1): 132.
Faith JJ, Hayete B, Thaden JT, Mogno I, et al. (2007). Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol 5(1): e8.
Meyer PE, Kontos K, Lafitte F and Bontempi G (2007). Information-theoretic inference of large transcriptional regulatory networks. EURASIP J Bioinform Syst Biol 2007(1): 79879.
Langfelder P and Horvath S (2008). WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 9(1): 559.
Meyer PE, Lafitte F and Bontempi G (2008). minet: AR/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics 9(1): 461.
Shannon P, Markiel A, Ozier O, Baliga NS, et al. (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11): 2498-2504.
Labhart P, Karmakar S, Salicru EM, Egan BS, et al. (2005). Identification of target genes in breast cancer cells directly regulated by the SRC-3/AIB1 coactivator. Proc Natl Acad Sci USA 102(5): 1339-1344.
Nestal de Moraes G, Delbue D, Silva KL, Robaina MC, et al. (2015). FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance. Cell Signal 27(12): 2496-2505.
Dawson SJ, Makretsov N, Blows FM, Driver KE, et al. (2010). BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer 103(5): 668-675.
Dang CV (2012). MYC on the path to cancer. Cell 149(1): 22-35.
Gerger A, Hofmann G, Langsenlehner U, Renner W, et al. (2009). Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk. Int J Colorectal Dis 24(2): 159-163.
Wang Y, Kuramitsu Y, Ueno T, Suzuki N, et al. (2012). Glyoxalase I (GLO1) is up-regulated in pancreatic cancerous tissues compared with related non-cancerous tissues. Anticancer Res 32(8): 3219-3222.
Hermann-Kleiter N, Klepsch V, Wallner S, Siegmund, K., et al. (2015). The nuclear orphan receptor NR2F6 is a central checkpoint for cancer immune surveillance. Cell rep 12(12): 2072-2085.
Wu CH, Sahoo D, Arvanitis C, Bradon N, et al. (2008). Combined analysis of murine and human microarrays and ChIP analysis reveals genes associated with the ability of MYC to maintain tumorigenesis. PLoS Genet 4(6): e1000090.
Grützmann R, Pilarsky C, Ammerpohl O, Lüttges J, et al. (2004). Gene expression profiling of microdissected pancreatic ductal carcinomas using high-density DNA microarrays. Neoplasia 6(5): 611-622.
Kobberup S, Nyeng P, Juhl K, Hutton J, et al. (2007). ETS"family genes in pancreatic development. Dev Dyn 236(11): 3100-3110.
Wu X, Deng F, Li Y, Daniels G, et al. (2015). ACSL4 promotes prostate cancer growth, invasion and hormonal resistance. Oncotarget 6(42): 44849.
Rüenauver K, Menon R, Svensson MA, Carlsson J, et al. (2014). Prognostic significance of YWHAZ expression in localized prostate cancer. Prostate Cancer Prostatic Dis 17(4): 310-314.
He H, Dai F, Yu L, She X, et al. (2002). Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Gene Expression 10(5-1): 231-242.