Skip to main content

miRNA Data Analysis: Next-Gen Sequencing

  • Protocol
  • First Online:
Next-Generation MicroRNA Expression Profiling Technology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 822))

Abstract

MicroRNAs (miRNAs) are short, noncoding RNAs that have the capacity to bind, capture, and silence hundreds of genes within and across diverse signaling pathways 1(Bartel, Cell 136:215–33, 2009) Specific sets of miRNAs characterize specific cell lineages of normal organisms and an increasing number of diseases have been shown to be associated with the dysregulation of specific miRNAs. Deep sequencing platforms have revealed unexpected complexity in relation to miRNAs, including 5′ and 3′-end-length heterogeneity and RNA editing. These insights not uncovered by previous microarray-based studies underscore the importance of data analysis tools that enable users to rapidly and easily analyze the unprecedented amounts of small RNA sequencing data that is emerging from next-generation sequencing platforms, such as Illumina/Solexa, SOLiD, and 454. In this chapter, we summarize the increasing number of analysis platforms that are available for miRNA discovery and profiling and the identification of functional miRNA–mRNA pairs in the context of biology and disease. We also discuss in greater detail our contributions to this effort.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

References

  1. Bartel, D. P. (2009) MicroRNAs: Target recognition and regulatory functions. Cell 136, 215–33.

    Article  PubMed  CAS  Google Scholar 

  2. Thomson, J. M., Parker, J., Perou, C. M., and Hammond, S. M.  (2004) A custom microarray platform for analysis of microRNA gene expression. Nat Methods 1, 47–53.

    Article  PubMed  CAS  Google Scholar 

  3. Miska, E. A., Alvarez-Saavedra, E., Townsend, M., Yoshii, A., Sestan, N., Rakic, P., et al. (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5, R68.

    Article  PubMed  Google Scholar 

  4. Mardis, E. R. (2008) The impact of next-generation sequencing technology on genetics. Trends Genet 24, 133–41.

    Article  PubMed  CAS  Google Scholar 

  5. Morozova, O. and Marra, M. A. (2008) Applications of next-generation sequencing technologies in functional genomics. Genomics 92, 255–64.

    Article  PubMed  CAS  Google Scholar 

  6. Creighton, C. J., Reid, J. G., Gunaratne, P. H. (2009) Expression profiling of microRNAs by deep sequencing. Brief Bioinformatics 10, 490–7.

    Article  PubMed  CAS  Google Scholar 

  7. Creighton, C. J., Nagaraja, A. K., Hanash, S. M., Matzuk, M. M., Gunaratne, P. H. (2008) A bioinformatics tool for linking gene expression profiling results with public databases of microRNA target predictions. RNA 14, 2290–6.

    Article  PubMed  CAS  Google Scholar 

  8. Griffiths-Jones, S., Moxon, S., Marshall, M., Khanna, A., Eddy, S. R, and Bateman, A. (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33, D121–4.

    Article  PubMed  CAS  Google Scholar 

  9. Sethupathy, P., Megraw, M., and Hatzi-georgiou, A. (2006) A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 3, 881–6.

    Article  PubMed  CAS  Google Scholar 

  10. Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P., and Burge, C. B. (2003) Prediction of mammalian microRNA targets. Cell 26, 787–98.

    Article  Google Scholar 

  11. Krek, A., Grün, D., Poy, M., Wolf, R., Rosenberg, L., Epstein, E., et al. (2005) Combinatorial microRNA target predictions. Nat Genet 37, 495–500.

    Article  PubMed  CAS  Google Scholar 

  12. Betel, D., Wilson, M., Gabow, A., Marks, D., and Sander, C. (2008) The microRNA.org resource: Targets and expression. Nucleic Acids Res 36, D149–53.

    Article  PubMed  CAS  Google Scholar 

  13. Jiang, Q., Wang, Y., Hao, Y., Juan, L., Teng, M., Zhang, X., et al. (2009) miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37, D98–104.

    Article  PubMed  CAS  Google Scholar 

  14. Nam, S., Kim, B., Shin, S., and Lee, S. (2008) miRGator: an integrated system for functional annotation of microRNAs. Nucleic Acids Res 36, D159–64.

    Article  PubMed  CAS  Google Scholar 

  15. Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A.,  et al.  (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102, 15545–50.

    Article  PubMed  CAS  Google Scholar 

  16. Kaya, K. D., Karakülah, G., Yakicier, C. M., Acar, A. C., Konu, O. (2011) mESAdb: microRNA expression and sequence analysis database Nucleic Acids Res 39, D170–80.

    Article  PubMed  Google Scholar 

  17. Pasaniuc, B., Zaitlen, N., and Halperin, E. (2010) Accurate estimation of expression levels of homologous genes in RNA-seq experiments. Proceedings of the Fourteenth International Conference on Research in Computational Biology 397–409.

    Google Scholar 

  18. Allen, E., Xie, Z., Gustafson, A. M., and Carrington, J. C. (2005) microRNA-directed phasing during trans-acting siRNA biogenesis in plants. Cell 121, 207–21.

    Article  PubMed  CAS  Google Scholar 

  19. Chen, H. M., Li, Y. H., Wu, S. H. (2007) Bioinformatic prediction and experimental validation of a microRNA-directed tandem trans-acting siRNA cascade in Arabidopsis. Proc Natl Acad Sci USA 104, 3318–23.

    Article  PubMed  CAS  Google Scholar 

  20. Hackenberg, M. and Matthiesen, R. (2008) Annotation-Modules: a tool for finding significant combinations of multisource annotations for gene lists. Bioinformatics 24, 1386–93.

    Article  PubMed  CAS  Google Scholar 

  21. Witten, I. H. and Frank, E. (2005) Data Mining: practical machine learning tools and techniques. Morgan Kaufmann Publishers, San Francisco.

    Google Scholar 

  22. Breiman, L. (2001) Random forests. Machine Learning 45, 28.

    Google Scholar 

  23. Dohm, J. C., Lottaz, C., Borodina, T., and Himmelbauer, H. (2008) Substantial biases in ultra-short read data sets from high-throughput DNA sequencing. Nucleic Acids Res 36, e105.

    Article  PubMed  Google Scholar 

  24. Reinartz, J., Bruyns, E., Lin, J. Z., Burcham, T., Brenner, S., Bowen, B., et al. (2002) Massively parallel signature sequencing (MPSS) as a tool for in-depth quantitative gene expression profiling in all organisms. Brief Funct Genomic Proteomic 1, 95–104.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  26. Mullan, L. J. and Bleasby, A. J. (2002) Short EMBOSS user guide. European molecular biology open software suite. Brief Bioinformatics 3, 92–4.

    Google Scholar 

  27. Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25, 3389–402.

    Article  PubMed  CAS  Google Scholar 

  28. Li, R., Yu, C., Li, Y., Lam, T. W, Yiu, S. M, Kristiansen, K., et al. (2009) SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25, 1966–7.

    Article  PubMed  CAS  Google Scholar 

  29. Griffiths-Jones, S., Saini, H. K., van Dongen, S., and Enright, A. J. (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36, D154–8.

    Article  PubMed  CAS  Google Scholar 

  30. Chen, N. (2004) Using RepeatMasker to identify repetitive elements in genomic sequences. Curr Protoc Bioinform 4, 108.

    Google Scholar 

  31. Audic, S., and Claverie, J. M. (1997) The significance of digital gene expression profiles. Genome Res 7, 986–95.

    PubMed  CAS  Google Scholar 

  32. Hofacker, I. L. (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31, 3429–31.

    Article  PubMed  CAS  Google Scholar 

  33. Coarfa, C., Yu, F., Miller, C. A., Chen, Z., Harris, R. A, Milosavljevic, A. (2010) Pash 3.0: A versatile software package for read mapping and integrative analysis of genomic and epigenomic variation using massively parallel DNA sequencing. BMC Bioinformatics 23, 572.

    Article  Google Scholar 

  34. Li, H. and Durbin, R. (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–60.

    Article  PubMed  CAS  Google Scholar 

  35. Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., et al. (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7, 335–6.

    Article  PubMed  CAS  Google Scholar 

  36. Kursa, M. B. and Rudnicki, W. R. (2010) Feature selection with the Boruta package. J Stat Softw 36, 1–13.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Preethi H. Gunaratne .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Gunaratne, P.H., Coarfa, C., Soibam, B., Tandon, A. (2012). miRNA Data Analysis: Next-Gen Sequencing. In: Fan, JB. (eds) Next-Generation MicroRNA Expression Profiling Technology. Methods in Molecular Biology, vol 822. Humana Press. https://doi.org/10.1007/978-1-61779-427-8_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-427-8_19

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-426-1

  • Online ISBN: 978-1-61779-427-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics