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A Bioconductor Based Workflow for Z-DNA Region Detection and Biological Inference

  • Halian Vilela
  • Tainá Raiol
  • Andrea Queiroz Maranhão
  • Maria Emília Walter
  • Marcelo M. Brígido
Part of the Lecture Notes in Computer Science book series (LNCS, volume 7409)

Abstract

Z-DNA is an alternative conformation of the DNA molecule implied in regulation of gene expression. However, the exact role of this structure in cell metabolism is not yet fully understood. Here we present a novel Z-DNA analysis workflow using the R software environment which aims to investigate Z-DNA forming regions (ZDRs) throughout the genome. It combines thermodynamic analysis of the well-known software Z-Catcher with biological data manipulation capabilities of several Bioconductor packages. We employed our methodology in the human chromosome 14 as a case study. With that, we established a correlation of ZDRs with transcription start sites (TSSs) which is in agreement with previous reports. In addition, our workflow was able to show that ZDRs which are positioned inside genes tend to occur in intronic sequences rather than exonic and that ZDRs upstream to TSSs may have a positive correlation with the up-regulation of RNA polymerase activity.

Keywords

Z-DNA ZDR Z-Catcher Bioconductor 

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References

  1. 1.
    Anders, S., Huber, W.: Differential expression analysis for sequence count data. Genome Biology 11, R106 (2010), http://www.bioconductor.org/packages/release/bioc/html/DESeq.html
  2. 2.
    Bioconductor: Open Source Software for Bioinformatics (2011), http://www.bioconductor.org/
  3. 3.
    Cairns, J., Spyrou, C., Stark, R., Smith, M.L., Lynch, A.G., Tavaré, S.: BayesPeaK–an R package for analysing ChIP-seq data. Bioinformatics 27(5), 713–714 (2011)CrossRefGoogle Scholar
  4. 4.
    Carlson, M., Pages, H., Aboyoun, P., Falcon, S., Morgan, M., Sarkar, D., Lawrence, M.: GenomicFeatures: Tools for making and manipulating transcript centric annotations (2011), http://www.bioconductor.org/packages/release/bioc/html/GenomicFeatures.html
  5. 5.
    Herbert, A., Lowenhaupt, K., Spitzner, J., Rich, A.: Chicken double-stranded RNA adenosine deaminase has apparent specificity for Z-DNA. Proc. Natl. Acad. Sci. USA 92(16), 7550–7554 (1995)CrossRefGoogle Scholar
  6. 6.
    Herbert, A., Rich, A.: The biology of left-handed Z-DNA. The Journal of Biological Chemistry 271(20), 11595–11598 (1996)CrossRefGoogle Scholar
  7. 7.
    Herbert, A.: RNA editing, introns and evolution. Trends in Genetics 12(1), 6–9 (1996)CrossRefGoogle Scholar
  8. 8.
    Ho, P.S., Ellison, M.J., Quigley, G.J., Rich, A.: A computer aided thermodynamic approach for predicting the formation of Z-DNA in naturally occurring sequences. The EMBO Journal 5(10), 2737–2744 (1986)Google Scholar
  9. 9.
    Joseph, R., Orlov, Y.L., Huss, M., Sun, W., Kong, S.L., Ukil, L., Pan, Y.F., Li, G., Lim, M., Thomsen, J.S., Ruan, Y., Clarke, N.D., Prabhakar, S., Cheung, E., Liu, E.T.: Integrative model of genomic factors for determining binding site selection by estrogen receptor-α. Molecular Systems Biology 6(456), 456 (2010)Google Scholar
  10. 10.
    Langmead, B., Trapnell, C., Pop, M., Salzberg, S.: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology 10(3), R25 (2009), http://bowtie-bio.sourceforge.net/index.shtml
  11. 11.
    Leinonen, R., Sugawara, H., Shumway, M.: The sequence read archive. Nucleic Acids Research 39(Database issue), D19–D21 (2011), http://www.ncbi.nlm.nih.gov/sra
  12. 12.
    Liu, L.F.: Supercoiling of the DNA Template during Transcription. Proceedings of the National Academy of Sciences 84(20), 7024–7027 (1987)CrossRefGoogle Scholar
  13. 13.
    Pages, H., Aboyoun, P., Lawrence, M.: IRanges: Infrastructure for manipulating intervals on sequences, http://www.bioconductor.org/packages/release/bioc/html/IRanges.html, r package version 1.12.6
  14. 14.
    Pepke, S., Wold, B., Mortazavi, A.: Computation for chip-seq and RNA-seq studies. Nature Methods 6(11s), S22–S32 (2009)Google Scholar
  15. 15.
    R Development Core Team: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria (2011), http://www.R-project.org, ISBN 3-900051-07-0
  16. 16.
    Rich, A., Nordheim, A., Wang, A.H.: The chemistry and biology of left-handed Z-DNA. Ann. Rev. Biochem. 53, 791–846 (1984)CrossRefGoogle Scholar
  17. 17.
    Rich, A., Zhang, S.: Z-DNA: the long road to biological function. Nature Reviews. Genetics 4, 566–573 (2003)CrossRefGoogle Scholar
  18. 18.
    Rosenbloom, K.R., Dreszer, T.R., Pheasant, M., Barber, G.P., Meyer, L.R., Pohl, A., Raney, B.J., Wang, T., Hinrichs, A.S., Zweig, A.S., Fujita, P.A., Learned, K., Rhead, B., Smith, K.E., Kuhn, R.M., Karolchik, D., Haussler, D., Kent, W.J.: ENCODE whole-genome data in the UCSC Genome Browser. Nucleic Acids Research 38(Database issue), D620–D625 (2010)Google Scholar
  19. 19.
    Sommer, B., Köhler, M., Sprengel, R., Seeburg, P.H.: RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67(1), 11–19 (1991)CrossRefGoogle Scholar
  20. 20.
    Tomlinson, I.M., Cook, G.P., Walter, G., Carter, N.P., Riethman, H., Buluwela, L., Rabbitts, T.H., Winter, G.: A complete map of the human immunoglobulin VH locus. Annals of the New York Academy of Sciences 764(1), 43–46 (1995)CrossRefGoogle Scholar
  21. 21.
    Xiao, J., Dröge, P., Li, J.: Detecting Z-DNA Forming Regions in the Human Genome. In: International Conference on Genome Informatics 2008 (2008)Google Scholar
  22. 22.
    Zhang, S., Lockshin, C., Herbert, A., Winter, E., Rich, A.: Zuotin, a putative Z-DNA binding protein in saccharomyces cerevisiae. EMBO J. 11(10), 3787–3796 (1992)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Halian Vilela
    • 1
  • Tainá Raiol
    • 1
  • Andrea Queiroz Maranhão
    • 1
  • Maria Emília Walter
    • 2
  • Marcelo M. Brígido
    • 1
  1. 1.Department of Cellular Biology, Institute of BiologyUniversity of BrasiliaBrasíliaBrazil
  2. 2.Department of Computer Science, Institute of Exact SciencesUniversity of BrasiliaBrasíliaBrazil

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