Obtaining miRNA‐Target Interaction Information from miRWalk2.0

Alisha Parveen1, Norbert Gretz1, Harsh Dweep1

1 Medical Research Center, Medical Faculty of Mannheim, University of Heidelberg, Mannheim
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 12.15
DOI:  10.1002/cpbi.14
Online Posting Date:  September, 2016
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library


miRWalk2.0 (http://zmf.umm.uni‐heidelberg.de/mirwalk2) is a freely accessible, regularly updated comprehensive archive supplying the largest available collection of predicted and experimentally verified miRNA‐target interactions, with various novel and unique features to assist the scientific community. Approximately 949 million interactions between 11,748 miRNAs, 308,700 genes, and 68,460 lncRNAs are documented in miRWalk2.0 with 5,146,217 different kinds of identifiers to offer a one‐stop site to collect an abundance of information. This article describes a schematic workflow on how to obtain miRNA‐target interactions from miRWalk2.0. © 2016 by John Wiley & Sons, Inc.

Keywords: micro RNA; miRNA; database; miRWalk2.0; target predictions; pathways; gene ontologies

PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Retrieving Predicted miRNA‐Target Interactions Using the PTM of miRWalk2.0
  • Basic Protocol 2: Retrieving Experimentally Verified miRNA‐Target Interactions Using the VTM of miRWalk2.0
  • Alternate Protocol 1: Holistic view of Gene‐miRNA Interactions or Download Page
  • Alternate Protocol 2: Customized Gene Set Builder System for miRNA
  • Guidelines for Understanding Results
  • Predicted Target Module
  • Validated Target Module
  • Commentary
  • Figures
PDF or HTML at Wiley Online Library


PDF or HTML at Wiley Online Library



Literature Cited

Literature Cited
  Bartel, D.P. 2004. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116:281‐297. doi: 10.1016/S0092‐8674(04)00045‐5.
  Brennecke, J., Stark, A., Russell, R.B., and Cohen, S.M. 2005. Principles of microRNA‐target recognition. PLoS Biol. 3:e85. doi: 10.1371/journal.pbio.0030085.
  Bushati, N. and Cohen, S.M. 2007. microRNA functions. Annu. Rev. Cell Dev. Biol. 23:175‐205. doi: 10.1146/annurev.cellbio.23.090506.123406.
  Chou, C.H., Chang, N.W., Shrestha, S., Hsu, S.D., Lin, Y.L., Lee, W.H., Yang, C.D., Hong, H.C., Wei, T.Y., Tu, S.J., Tsai, T.R., Ho, S.Y., Jian, T.Y., Wu, H.Y., Chen, P.R., Lin, N.C., Huang, H.T., Yang, T.L., Pai, C.Y., Tai, C.S., Chen, W.L., Huang, C.Y., Liu, C.C., Weng, S.L., Liao, K.W., Hsu, W.L., and Huang, H.D. 2016. miRTarBase 2016: Updates to the experimentally validated miRNA‐target interactions database. Nucleic Acids Res. 44:D239‐247. doi: 10.1093/nar/gkv1258.
  Dai, Q., Zhao, J., Qi, X., Xu, W., He, X., Guo, M., Dweep, H., Cheng, W.H., Luo, Y., Xia, K., Gretz, N., and Huang, K. 2014. MicroRNA profiling of rats with ochratoxin A nephrotoxicity. BMC Genomics 15:333. doi: 10.1186/1471‐2164‐15‐333.
  Dalmay, T. 2013. Mechanism of miRNA‐mediated repression of mRNA translation. Essays Biochem. 54:29‐38. doi: 10.1042/bse0540029.
  Dewing, A.S., Rueli, R.H., Robles, M.J., Nguyen‐Wu, E.D., Zeyda, T., Berry, M.J., and Bellinger, F.P. 2012. Expression and regulation of mouse selenoprotein P transcript variants differing in non‐coding RNA. RNA Biol. 9:1361‐1369. doi: 10.4161/rna.22290.
  Durand, C., Roeth, R., Dweep, H., Vlatkovic, I., Decker, E., Schneider, K.U., and Rappold, G. 2011. Alternative splicing and nonsense‐mediated RNA decay contribute to the regulation of SHOX expression. PloS ONE 6:e18115. doi: 10.1371/journal.pone.0018115.
  Dweep, H. and Gretz, N. 2015. miRWalk2.0: A comprehensive atlas of microRNA‐target interactions. Nat. Methods 12:697. doi: 10.1038/nmeth.3485.
  Dweep, H., Sticht, C., Pandey, P., and Gretz, N. 2011. miRWalk–database: Prediction of possible miRNA binding sites by “walking” the genes of three genomes. J. Biomed. Inform. 44:839‐847. doi: 10.1016/j.jbi.2011.05.002.
  Dweep, H., Georgiou, G.D., Gretz, N., Deltas, C., Voskarides, K., and Felekkis, K. 2013a. CNVs‐microRNAs interactions demonstrate unique characteristics in the human genome. An interspecies in silico analysis. PloS ONE 8:e81204. doi: 10.1371/journal.pone.0081204.
  Dweep, H., Sticht, C., Kharkar, A., Pandey, P., and Gretz, N. 2013b. Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: Using PKD/Mhm rat model. PloS ONE 8:e53780. doi: 10.1371/journal.pone.0053780.
  Dweep, H., Sticht, C., and Gretz, N. 2013c. In‐silico algorithms for the screening of possible microRNA binding sites and their interactions. Curr. Genomics 14:127‐136. doi: 10.2174/1389202911314020005.
  Elcheva, I., Goswami, S., Noubissi, F.K., and Spiegelman, V.S. 2009. CRD‐BP protects the coding region of betaTrCP1 mRNA from miR‐183‐mediated degradation. Mol. Cell 35:240‐246. doi: 10.1016/j.molcel.2009.06.007.
  Fang, Z. and Rajewsky, N. 2011. The impact of miRNA target sites in coding sequences and in 3′UTRs. PLoS ONE 6:e18067. doi: 10.1371/journal.pone.0018067.
  Forman, J.J. and Coller, H.A. 2010. The code within the code: MicroRNAs target coding regions. Cell Cycle 9:1533‐1541. doi: 10.4161/cc.9.8.11202.
  Forman, J.J., Legesse‐Miller, A., and Coller, H.A. 2008. A search for conserved sequences in coding regions reveals that the let‐7 microRNA targets Dicer within its coding sequence. Proc. Natl. Acad. Sci. U.S.A. 105:14879‐14884. doi: 10.1073/pnas.0803230105.
  Gaynullina, D., Dweep, H., Gloe, T., Tarasova, O.S., Sticht, C., Gretz, N., and Schubert, R. 2015. Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development. Sci. Rep. 5:11106. doi: 10.1038/srep11106.
  Hausser, J., Syed, A.P., Bilen, B., and Zavolan, M. 2013. Analysis of CDS‐located miRNA target sites suggests that they can effectively inhibit translation. Genome Res. 23:604‐615. doi: 10.1101/gr.139758.112.
  Kim, D.H., Saetrom, P., Snove, O. Jr., and Rossi, J.J. 2008. MicroRNA‐directed transcriptional gene silencing in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 105:16230‐16235. doi: 10.1073/pnas.0808830105.
  Kozomara, A. and Griffiths‐Jones, S. 2014. miRBase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42:D68‐73. doi: 10.1093/nar/gkt1181.
  Lai, E.C., Wiel, C., and Rubin, G.M. 2004. Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes. RNA 10:171‐175. doi: 10.1261/rna.5191904.
  Lutter, D., Marr, C., Krumsiek, J., Lang, E.W., and Theis, F.J. 2010. Intronic microRNAs support their host genes by mediating synergistic and antagonistic regulatory effects. BMC Genomics 11:224. doi: 10.1186/1471‐2164‐11‐224.
  Papagregoriou, G., Erguler, K., Dweep, H., Voskarides, K., Koupepidou, P., Athanasiou, Y., Pierides, A., Gretz, N., Felekkis, K.N., and Deltas, C. 2012. A miR‐1207‐5p binding site polymorphism abolishes regulation of HBEGF and is associated with disease severity in CFHR5 nephropathy. PloS ONE 7:e31021. doi: 10.1371/journal.pone.0031021.
  Park, J.H. and Shin, C. 2014. MicroRNA‐directed cleavage of targets: Mechanism and experimental approaches. BMB Rep. 47:417‐423. doi: 10.5483/BMBRep.2014.47.8.109.
  Place, R.F., Li, L.C., Pookot, D., Noonan, E.J., and Dahiya, R. 2008. MicroRNA‐373 induces expression of genes with complementary promoter sequences. Proc. Natl. Acad. Sci. U.S.A. 105:1608‐1613. doi: 10.1073/pnas.0707594105.
  Schnall‐Levin, M., Rissland, O.S., Johnston, W.K., Perrimon, N., Bartel, D.P., and Berger, B. 2011. Unusually effective microRNA targeting within repeat‐rich coding regions of mammalian mRNAs. Genome Res. 21:1395‐1403. doi: 10.1101/gr.121210.111.
  Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., and Mesirov, J.P. 2005. Gene set enrichment analysis: A knowledge‐based approach for interpreting genome‐wide expression profiles. Proc. Natl. Acad. Sci. U.S.A. 102:15545‐15550. doi: 10.1073/pnas.0506580102.
  Tay, Y., Zhang, J., Thomson, A.M., Lim, B., and Rigoutsos, I. 2008. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455:1124‐1128. doi: 10.1038/nature07299.
  Yoon, J.H., Abdelmohsen, K., and Gorospe, M. 2014. Functional interactions among microRNAs and long noncoding RNAs. Semin. Cell Dev. Biol. 34:9‐14. doi: 10.1016/j.semcdb.2014.05.015.
  Younger, S.T., Pertsemlidis, A., and Corey, D.R. 2009. Predicting potential miRNA target sites within gene promoters. Bioorg. Med. Chem. Lett. 19:3791‐3794. doi: 10.1016/j.bmcl.2009.04.032.
  Zhou, H. and Rigoutsos, I. 2014. MiR‐103a‐3p targets the 5′ UTR of GPRC5A in pancreatic cells. RNA 20:1431‐1439. doi: 10.1261/rna.045757.114.
Internet Resources
  Information about the resources used to collate data sets on genes, miRNAs, biological signaling cascades and putative as well as experimentally verified miRNA‐target interaction.
  A complete list of databases that have been hyperlinked to annotate the result pages of miRWalk2.0.
PDF or HTML at Wiley Online Library