Skip to main content

Identification of Disease–miRNA Networks Across Different Cancer Types Using SWIM

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1970))

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) involved in several biological processes and diseases. MiRNAs regulate gene expression at the posttranscriptional level, mostly downregulating their targets by binding specific regions of transcripts through imperfect sequence complementarity. Prediction of miRNA-binding sites is challenging, and target prediction algorithms are usually based on sequence complementarity. In the last years, it has been shown that by adding miRNA and protein coding gene expression, we are able to build tissue-, cell line-, or disease-specific networks improving our understanding of complex biological scenarios. In this chapter, we present an application of a recently published software named SWIM, that allows to identify key genes in a network of interactions by defining appropriate “roles” of genes according to their local/global positioning in the overall network. Furthermore, we show how the SWIM software can be used to build miRNA–disease networks, by applying the approach to tumor data obtained from The Cancer Genome Atlas (TCGA).

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Costa FF (2008) Non-coding RNAs, epigenetics and complexity. Gene 410(1):9–17

    Article  CAS  PubMed  Google Scholar 

  2. Mattick JS (2009) The genetic signatures of noncoding RNAs. PLoS Genet 5(4):10–1371

    Article  Google Scholar 

  3. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136(2):215–233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight. Nat Rev Genet 9(2):102–114

    Article  CAS  PubMed  Google Scholar 

  5. Koziol MJ, Rinn JL (2010) RNA traffic control of chromatin complexes. Curr Opin Genet Dev 20(2):142–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  PubMed  Google Scholar 

  7. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113(1):25–36

    Article  CAS  PubMed  Google Scholar 

  8. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5):843–854

    Article  CAS  PubMed  Google Scholar 

  9. Catalanotto C, Cogoni C, Zardo G (2016) MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci 17:1712

    Article  PubMed Central  Google Scholar 

  10. Garzon R, Calin GA, Croce CM (2009) MicroRNAs in cancer. Annu Rev Med 60:167–179

    Article  CAS  PubMed  Google Scholar 

  11. Gaur A, Jewell DA, Liang Y, Ridzon D, Moore JH, Chen C, Ambros VR, Israel MA (2007) Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res 67(6):2456–2468

    Article  CAS  PubMed  Google Scholar 

  12. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu C-G, Alder H, Calin GA, Ménard S, Croce CM (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18):8699–8707

    Article  CAS  PubMed  Google Scholar 

  13. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435(7043):834–838

    Article  CAS  PubMed  Google Scholar 

  14. Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449(7163):682–688

    Article  CAS  PubMed  Google Scholar 

  15. Peng Y, Croce CM (2016) The role of MicroRNAs in human cancer. Signal Transduct Target Ther 1:15004

    Article  PubMed  PubMed Central  Google Scholar 

  16. Reddy KB (2015) MicroRNA (miRNA) in cancer. Cancer Cell Int 15:38

    Article  PubMed  PubMed Central  Google Scholar 

  17. Spizzo R, Nicoloso MS, Croce CM, Calin GA (2009) Snapshot: microRNAs in cancer. Cell 137(3):586–5861

    Article  CAS  PubMed  Google Scholar 

  18. Rual J-F et al (2005) Towards a proteome-scale map of the human protein–protein interaction network. Nature 437:1173–1178

    Article  CAS  PubMed  Google Scholar 

  19. Stelzl U et al (2005) A human protein-protein interaction network: a resource for annotating the proteome. Cell 122:957–968

    Article  CAS  PubMed  Google Scholar 

  20. Duarte NC et al (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci U S A 104:1777–1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fell DA, Wagner A (2000) The small world of metabolism. Nat Biotechnol 18:1121–1122

    Article  CAS  PubMed  Google Scholar 

  22. Jeong H et al (2000) The large-scale organization of metabolic networks. Nature 407:651–654

    Article  CAS  PubMed  Google Scholar 

  23. Carninci P et al (2005) The transcriptional landscape of the mammalian genome. Science 309:1559–1563

    Article  CAS  PubMed  Google Scholar 

  24. Stuart JM et al (2003) A gene-coexpression network for global discovery of conserved genetic modules. Science 302:249–255

    Article  CAS  PubMed  Google Scholar 

  25. Paci P, Colombo T, Fiscon G, Gurtner A, Pavesi G, Farina L (2017) SWIM: a computational tool to unveiling crucial nodes in complex biological networks. Sci Rep 7:44797. https://doi.org/10.1038/srep44797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Barabási A-L, Gulbahce N, Loscalzo J (2011) Network medicine. A network-based approach to human disease. Nat Rev Genet 12:56–68

    Article  PubMed  PubMed Central  Google Scholar 

  27. Palumbo MC, Zenoni S, Fasoli M, Massonnet M, Farina L, Castiglione F, Pezzotti M, Paci P (2014) Integrated network analysis identifies fight-club nodes as a class of hubs encompassing key putative switch genes that induce major transcriptome reprogramming during grapevine development. Plant Cell 26(12):4617–4635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fiscon G, Conte F, Licursi V, Nasi S, Paci P (2018) Computational identification of specific genes for glioblastoma stem-like cells identity. Sci Rep 8:7769. https://doi.org/10.1038/s41598-018-26081-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B Methodol 57:289–300

    Google Scholar 

  30. Hartigan JA (1973) Clustering. Annu Rev Biophys Bioeng 2:81–101

    Article  CAS  PubMed  Google Scholar 

  31. Lisboa PJ, Etchells TA, IH J, Chambers SJ (2013) Finding reproducible cluster partitions for the k-means algorithm. BMC Bioinformatics 14(1):1

    Article  Google Scholar 

  32. Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP, Vidal M (2004) Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature 430:88–93

    Article  CAS  PubMed  Google Scholar 

  33. Guimera R, Amaral LAN (2005a) Cartography of complex networks: modules and universal roles. J Stat Mech P02001:1–13

    Google Scholar 

  34. Guimera R, Amaral LAN (2005b) Functional cartography of complex metabolic networks. Nature 433:895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM, Cancer Genome Atlas Research Network (2013) The cancer genome atlas pan-cancer analysis project. Nat Genet 45(10):1113–1120

    Article  PubMed  PubMed Central  Google Scholar 

  36. Goh K-I, Cusick ME, Valle D, Childs B, Vidal M, Barabási A-L (2007) The human disease network. Proc Natl Acad Sci 104(21):8685–8690. https://doi.org/10.1073/pnas.0701361104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cizeron-Clairac G et al (2015) M iR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers? BMC Cancer 15(1):499

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fan Y et al (2018) miR-122 promotes metastasis of clear-cell renal cell carcinoma by downregulating Dicer. Int J Cancer 142(3):547–560

    Article  CAS  PubMed  Google Scholar 

  39. Nunez Lopez YO et al (2018) Characteristic miRNA expression signature and random forest survival analysis identify potential cancer-driving miRNAs in a broad range of head and neck squamous cell carcinoma subtypes. Rep Pract Oncol Radiother 23(1):6–20

    Article  PubMed  Google Scholar 

  40. Volinia S et al (2012) Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci 109(8):3024–3029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Agarwal V, Bell GW, Nam J-W, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. elife 4:05005

    Article  Google Scholar 

  42. Chou C-H et al (2015) miRTarbase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res 44(D1):239–247

    Article  Google Scholar 

Download references

Acknowledgments

G.F., F.C., and P.P. have been supported by SysBioNet, Italian Roadmap Research Infrastructures 2012. FR has been supported by the Novo Nordisk Foundation (grant agreement NNF14CC0001). MP would like to acknowledge funds from the Flagship project InterOmics (PB.P05, CUP B91J12000270001) funded by the Italian Ministry of Education and University (MIUR) and National Research Council (CNR) organizations, project RepeatALS funded by Arisla (Italian Society for Research on Amyotrophic Lateral Sclerosis), the PRIN 201534HNXC project funded by the Italian MIUR, and the joint CNR IIT-IFC Laboratory of Integrative Systems Medicine (LISM). The results reported in this chapter are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.

Conflict of Interest: The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Francesco Russo or Paola Paci .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Fiscon, G., Conte, F., Farina, L., Pellegrini, M., Russo, F., Paci, P. (2019). Identification of Disease–miRNA Networks Across Different Cancer Types Using SWIM. In: Laganà, A. (eds) MicroRNA Target Identification. Methods in Molecular Biology, vol 1970. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9207-2_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9207-2_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9206-5

  • Online ISBN: 978-1-4939-9207-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics