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Analysis of MicroRNA Expression Using Machine Learning

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miRNomics: MicroRNA Biology and Computational Analysis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1107))

Abstract

The systematic analysis of miRNA expression and its potential mRNA targets constitutes a basal objective in miRNA research in addition to miRNA gene detection and miRNA target prediction. In this chapter we address methodical issues of miRNA expression analysis using self-organizing maps (SOM), a neural network machine learning algorithm with strong visualization and second-level analysis capabilities widely used to categorize large-scale, high-dimensional data. We shortly review selected experimental and theoretical aspects of miRNA expression analysis. Then, the protocol of our SOM method is outlined with special emphasis on miRNA/mRNA coexpression. The method allows extracting differentially expressed RNA transcripts, their functional context, and also characterization of global properties of expression states and profiles. In addition to the separate study of miRNA and mRNA expression landscapes, we propose the combined analysis of both entities using a covariance SOM.

Henry Wirth and Mehmet Volkan Çakir have contributed equally to this chapter.

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References

  1. Mendes ND, Freitas AT, Sagot M-F (2009) Current tools for the identification of miRNA genes and their targets. Nucleic Acids Res 37:2419–2433

    Article  PubMed  CAS  Google Scholar 

  2. Kim S-K, Nam J-W, Rhee J-K, Lee W-J, Zhang B-T (2006) miTarget: microRNA target gene prediction using a support vector machine. BMC Bioinformatics 7:411

    Article  PubMed  Google Scholar 

  3. Wang X, El Naqa IM (2008) Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24:325–332

    Article  PubMed  Google Scholar 

  4. Yousef M, Jung S, Kossenkov AV, Showe LC, Showe MK (2007) Naïve Bayes for microRNA target predictions—machine learning for microRNA targets. Bioinformatics 23:2987–2992

    Article  PubMed  CAS  Google Scholar 

  5. Heikkinen L, Kolehmainen M, Wong G (2011) Prediction of microRNA targets in Caenorhabditis elegans using a self-organizing map. Bioinformatics 27(9):1247–1254

    Article  PubMed  CAS  Google Scholar 

  6. Kohonen T (1982) Self-organized formation of topologically correct feature maps. Biol Cybern 43:59–69

    Article  Google Scholar 

  7. Tamayo P, Slonim D, Mesirov J, Zhu Q, Kitareewan S, Dmitrovsky E, Lander ES, Golub TR (1999) Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci U S A 96:2907–2912

    Article  PubMed  CAS  Google Scholar 

  8. Törönen P, Kolehmainen M, Wong G, Castrén E (1999) Analysis of gene expression data using self-organizing maps. FEBS Lett 451:142–146

    Article  PubMed  Google Scholar 

  9. Eichler GS, Huang S, Ingber DE (2003) Gene expression dynamics inspector (GEDI): for integrative analysis of expression profiles. Bioinformatics 19:2321–2322

    Article  PubMed  CAS  Google Scholar 

  10. Wirth H, Loeffler M, von Bergen M, Binder H (2011) Expression cartography of human tissues using self organizing maps. BMC Bioinformatics 12:306

    Article  PubMed  Google Scholar 

  11. Lu J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  PubMed  CAS  Google Scholar 

  12. Yin JQ, Zhao RC, Morris KV (2008) Profiling microRNA expression with microarrays. Trends Biotechnol 26:70–76

    Article  PubMed  CAS  Google Scholar 

  13. Wang Z, Yang B (eds) (2010) MicroRNA expression detection methods. Springer, Heidelberg

    Google Scholar 

  14. Kong W, Zhao J-J, He L, Cheng JQ (2009) Strategies for profiling MicroRNA expression. J Cell Physiol 218:22–25

    Article  PubMed  CAS  Google Scholar 

  15. Git A, Dvinge H, Salmon-Divon M, Osborne M, Kutter C, Hadfield J, Bertone P, Caldas C (2010) Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA 16:991–1006

    Article  PubMed  CAS  Google Scholar 

  16. Sato F, Tsuchiya S, Terasawa K, Tsujimoto G (2009) Intra-platform repeatability and inter-platform comparability of MicroRNA microarray technology. PLoS One 4:e5540

    Article  PubMed  Google Scholar 

  17. Fasold M, Langenberger D, Binder H, Stadler PF, Hoffmann S (2011) DARIO: a ncRNA detection and analysis tool for next-generation sequencing experiments. Nucleic Acids Res 39:W112–W117

    Article  PubMed  CAS  Google Scholar 

  18. Linsen SEV et al (2009) Limitations and possibilities of small RNA digital gene expression profiling. Nat Methods 6:474–476

    Article  PubMed  CAS  Google Scholar 

  19. Binder, H.; Preibisch, S.; Berger, H. Calibration of microarray gene-expression data. In Methods in Molecular Biology; Grützmann, R.; Pilarski, C., Eds.; Humana Press: New York, 2009; Vol. 575, pp. 376–407

    Google Scholar 

  20. Nelson PT, Wang W-X, Wilfred BR, Tang G (2008) Technical variables in high-throughput miRNA expression profiling: much work remains to be done. Biochim Biophys Acta 1779:758–765

    Article  PubMed  CAS  Google Scholar 

  21. Yuan J, Reed A, Chen F, Stewart CN (2006) Statistical analysis of real-time PCR data. BMC Bioinformatics 7:85

    Article  PubMed  Google Scholar 

  22. Meacham F, Boffelli D, Dhahbi J, Martin D, Singer M, Pachter L (2011) Identification and correction of systematic error in high-throughput sequence data. BMC Bioinformatics 12:451

    Article  PubMed  Google Scholar 

  23. Meyer S, Pfaffl M, Ulbrich S (2010) Normalization strategies for microRNA profiling experiments: a ‘normal’ way to a hidden layer of complexity? Biotechnol Lett 32:1777–1788

    Article  PubMed  CAS  Google Scholar 

  24. Chang K, Mestdagh P, Vandesompele J, Kerin M, Miller N (2010) MicroRNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC Cancer 10:173

    Article  PubMed  CAS  Google Scholar 

  25. Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A Comparison of Normalization Methods for High Density Oligonucleotide Array Data Based on Variance and Bias. Bioinformatics 19:9

    Google Scholar 

  26. Dudoit S, Yang YH, Callow MJ, Speed TP (2002) Statistical methods for identifying genes with differential expression in replicated cDNA microarray experiments. Stat Sin 12:111–139

    Google Scholar 

  27. Smyth G, Speed T (2003) Normalization of cDNA microarray data. Methods 31:265–273

    Article  PubMed  CAS  Google Scholar 

  28. Wirth H, von Bergen M, Binder H (2012) Mining SOM expression portraits: feature selection and integrating concepts of molecular function. BioData Min 5:18

    Article  PubMed  Google Scholar 

  29. Cakir V, Wirth H, Hopp L, Binder H (2013) miRNA expression landscapes in stem cells, tissues and cancer. Methods of Molecular Biology

    Google Scholar 

  30. Guo Y, Eichler GS, Feng Y, Ingber DE, Huang S (2006) Towards a holistic, yet gene-centered analysis of gene expression profiles: a case study of human lung cancers. J Biomed Biotechnol 2006, Article ID 69141

    Google Scholar 

  31. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  32. Opgen-Rhein R, Strimmer K (2007) Accurate Ranking of Differentially Expressed Genes by a Distribution-Free Shrinkage Approach. Statist. Appl Genet Mol Biol 6

    Google Scholar 

  33. Strimmer K (2008) A unified approach to false discovery rate estimation. BMC Bioinformatics 9:303

    Article  PubMed  Google Scholar 

  34. Chi SW, Zang JB, Mele A, Darnell RB (2009) Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 460:479–486

    PubMed  CAS  Google Scholar 

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Acknowledgements

This publication is supported by LIFE—Center for Civilization Diseases, Universität Leipzig. LIFE is funded by the European ERDF fund and by the Free State of Saxony.

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Wirth, H., Çakir, M.V., Hopp, L., Binder, H. (2014). Analysis of MicroRNA Expression Using Machine Learning. In: Yousef, M., Allmer, J. (eds) miRNomics: MicroRNA Biology and Computational Analysis. Methods in Molecular Biology, vol 1107. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-748-8_16

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  • DOI: https://doi.org/10.1007/978-1-62703-748-8_16

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-747-1

  • Online ISBN: 978-1-62703-748-8

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