Advertisement

Computational Approaches to the Detection and Analysis of Sequences with Intramolecular G-Quadruplex Forming Potential

  • Paul Ryvkin
  • Steve G. Hershman
  • Li-San WangEmail author
  • F. Brad Johnson
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 608)

Abstract

Sequences with the potential to form intramolecular G-quadruplexes (G4-structures) are found in highly nonrandom distributions in the genomes of diverse organisms. These sequences are associated with nucleic acid metabolic processes ranging from transcription and translation to recombination and telomere function. Here we review different computational methods for identifying potential G4-forming sequences and provide protocols for their implementation. We also discuss methods for assessing the significance and specificity of associations between the sequences and different biological functions.

Key words

G-quadruplex G4-DNA Bioinformatics Computational biology 

Notes

Acknowledgments

We thank Jay Johnson, Kajia Cao, Marina Kozak, Alex Chavez, Jasmine Smith, and Qijun Chen for advice and discussions. This work was supported by NIH grants R01-AG021521, P01-AG031862, and a U. Penn Institute on Aging Pilot Grant.

References

  1. 1.
    Maizels N (2006) Dynamic roles for G4 DNA in the biology of eukaryotic cells. Nat Struct Mol Biol 13:1055–1059CrossRefPubMedGoogle Scholar
  2. 2.
    Johnson JE, Smith JS, Kozak ML, Johnson FB (2008) In vivo veritas: using yeast to probe the biological functions of G-quadruplexes. Biochimie 90:1250–1263CrossRefPubMedGoogle Scholar
  3. 3.
    Lane AN, Chaires JB, Gray RD, Trent JO (2008) Stability and kinetics of G-quadruplex structures. Nucleic Acids Res 36:5482–5515CrossRefPubMedGoogle Scholar
  4. 4.
    Webba da Silva M (2007) Geometric formalism for DNA quadruplex folding. Chemistry 13:9738–9745CrossRefPubMedGoogle Scholar
  5. 5.
    Bugaut A, Balasubramanian S (2008) A sequence-independent study of the influence of short loop lengths on the stability and topology of intramolecular DNA G-quadruplexes. Biochemistry 47:689–697CrossRefPubMedGoogle Scholar
  6. 6.
    Fry M (2007) Tetraplex DNA and its interacting proteins. Front Biosci 12:4336–4351CrossRefPubMedGoogle Scholar
  7. 7.
    Rawal P, Kummarasetti VB, Ravindran J, Kumar N, Halder K, Sharma R et al (2006) Genome-wide prediction of G4 DNA as regulatory motifs: role in Escherichia coli global regulation. Genome Res 16:644–655CrossRefPubMedGoogle Scholar
  8. 8.
    Huppert JL, Balasubramanian S (2005) Prevalence of quadruplexes in the human genome. Nucleic Acids Res 33:2908–2916CrossRefPubMedGoogle Scholar
  9. 9.
    Todd AK, Johnston M, Neidle S (2005) Highly prevalent putative quadruplex sequence motifs in human DNA. Nucleic Acids Res 33:2901–2907CrossRefPubMedGoogle Scholar
  10. 10.
    Eddy J, Maizels N (2006) Gene function correlates with potential for G4 DNA formation in the human genome. Nucleic Acids Res 34:3887–3896CrossRefPubMedGoogle Scholar
  11. 11.
    Hershman SG, Chen Q, Lee JY, Kozak ML, Yue P, Wang L-S et al (2008) Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae. Nucleic Acids Res 36:144–156CrossRefPubMedGoogle Scholar
  12. 12.
    Bates P, Mergny JL, Yang D (2007) Quartets in G-major. The First International Meeting on Quadruplex DNA. EMBO Rep 8:1003–1010PubMedGoogle Scholar
  13. 13.
    Guedin A, De Cian A, Gros J, Lacroix L, Mergny JL (2008) Sequence effects in single-base loops for quadruplexes. Biochimie 90:686–696CrossRefPubMedGoogle Scholar
  14. 14.
    Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100:9440–9445CrossRefPubMedGoogle Scholar
  15. 15.
    Strimmer K (2008) A unified approach to false discovery rate estimation. BMC Bioinformatics 9:303CrossRefPubMedGoogle Scholar
  16. 16.
    Ponty Y, Termier M, Denise A (2006) GenRGenS: software for generating random genomic sequences and structures. Bioinformatics 22:1534–1535CrossRefPubMedGoogle Scholar
  17. 17.
    Eddy J, Maizels N (2008) Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes. Nucleic Acids Res 36:1321–1333CrossRefPubMedGoogle Scholar
  18. 18.
    Harbison CT, Gordon DB, Lee TI, Rinaldi NJ, Macisaac KD, Danford TW et al (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431:91–104CrossRefGoogle Scholar
  19. 19.
    Kikin O, D’Antonio L (2006) QGRS Mapper: a web-based server for predicting G-quadruplexes in nucleotide sequences. Nucleic Acids Res 34:W676–W682CrossRefPubMedGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Paul Ryvkin
    • 1
  • Steve G. Hershman
    • 2
  • Li-San Wang
    • 3
    Email author
  • F. Brad Johnson
    • 4
  1. 1.Department of Pathology and Laboratory Medicine, Penn Center for Bioinformatics, and Graduate Group in Genomics and Computational BiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of Pathology and Laboratory Medicine, Institute on Aging, Penn Center for Bioinformatics, and Graduate Group in Genomics and Computational BiologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.Department of Pathology and Laboratory Medicine, Institute on AgingUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations