Skip to main content

Mining Regulatory Network Connections by Ranking Transcription Factor Target Genes Using Time Series Expression Data

  • Protocol
  • First Online:
Data Mining for Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 939))

  • 3739 Accesses

Abstract

Reverse engineering the gene regulatory network is challenging because the amount of available data is very limited compared to the complexity of the underlying network. We present a technique addressing this problem through focussing on a more limited problem: inferring direct targets of a transcription factor from short expression time series. The method is based on combining Gaussian process priors and ordinary differential equation models allowing inference on limited potentially unevenly sampled data. The method is implemented as an R/Bioconductor package, and it is demonstrated by ranking candidate targets of the p53 tumour suppressor.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10:252–263

    Article  PubMed  CAS  Google Scholar 

  2. Pertea M, Salzberg SL (2010) Between a chicken and a grape: estimating the number of human genes. Genome Biol 11:206

    Article  PubMed  Google Scholar 

  3. Sontag ED (2002) For differential equations with r parameters, 2r+1 experiments are enough for identification. J Nonlinear Sci 12:553–583

    Article  CAS  Google Scholar 

  4. Stark J, Brewer D, Barenco M, Tomescu D, Callard R, Hubank M (2003) Reconstructing gene networks: what are the limits? Biochem Soc Trans 31:1519–1525

    Article  PubMed  CAS  Google Scholar 

  5. Gao P, Honkela A, Rattray M, Lawrence ND (2008) Gaussian process modelling of latent chemical species: applications to inferring transcription factor activities. Bioinformatics 24:i70–i75

    Article  PubMed  Google Scholar 

  6. Honkela A, Girardot C, Gustafson EH, Liu Y-H, Furlong EEM, Lawrence ND, Rattray M (2010) Model-based method for transcription factor target identification with limited data. Proc Natl Acad Sci USA 107:7793–7798

    Article  PubMed  CAS  Google Scholar 

  7. Barenco M, Tomescu D, Brewer D, Callard R, Stark J, Hubank M (2006) Ranked prediction of p53 targets using hidden variable dynamic modeling. Genome Biol 7:R25

    Article  PubMed  Google Scholar 

  8. Barenco M, Papouli E, Shah S, Brewer D, Miller CJ, Hubank M (2009) rHVDM: An R package to predict the activity and targets of a transcription factor. Bioinformatics 25:419–420

    Article  PubMed  CAS  Google Scholar 

  9. Della Gatta G, Bansal M, Ambesi-Impiombato A, Antonini D, Missero C, di Bernardo D (2008) Direct targets of the TRP63 transcription factor revealed by a combination of gene expression profiling and reverse engineering. Genome Res 18:939–948

    Article  PubMed  CAS  Google Scholar 

  10. Barenco M, Brewer D, Papouli E, Tomescu D, Callard R, Stark J, Hubank M (2009) Dissection of a complex transcriptional response using genome-wide transcriptional modelling. Mol Syst Biol 5:327

    Article  PubMed  Google Scholar 

  11. Gentleman RC et al (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80

    Article  PubMed  Google Scholar 

  12. Pearson RD, Liu X, Sanguinetti G, Milo M, Lawrence ND, Rattray M (2009) puma: A bioconductor package for propagating uncertainty in microarray analysis. BMC Bioinformatics 10:211

    Article  PubMed  Google Scholar 

  13. Du P, Kibbe WA, Lin SM (2008) lumi: A pipeline for processing illumina microarray. Bioinformatics 24:1547–1548

    Article  PubMed  CAS  Google Scholar 

  14. Honkela A, Milo M, Holley M, Rattray M, Lawrence ND (2010) Ranking of gene regulators through differential equations and Gaussian processes. Proceedings of 2010 IEEE international workshop on machine learning for signal processing (MLSP 2010), Kittilä, Finland, pp 154–159

    Google Scholar 

  15. Smeenk L, van Heeringen SJ, Koeppel M, van Driel MA, Bartels SJJ, Akkers RC, Denissov S, Stunnenberg HG, Lohrum M (2008) Characterization of genome-wide p53-binding sites upon stress response. Nucleic Acids Res 36:3639–3654

    Article  PubMed  CAS  Google Scholar 

  16. Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, Diekhans M, Dreszer TR, Giardine BM, Harte RA, Hillman-Jackson J, Hsu F, Kirkup V, Kuhn RM, Learned K, Li CH, Meyer LR, Pohl A, Raney BJ, Rosenbloom KR, Smith KE, Haussler D, Kent WJ (2011) The UCSC Genome Browser database: update 2011. Nucleic Acids Res 39:D876–D882

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antti Honkela .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this protocol

Cite this protocol

Honkela, A., Rattray, M., Lawrence, N.D. (2013). Mining Regulatory Network Connections by Ranking Transcription Factor Target Genes Using Time Series Expression Data. In: Mamitsuka, H., DeLisi, C., Kanehisa, M. (eds) Data Mining for Systems Biology. Methods in Molecular Biology, vol 939. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-107-3_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-107-3_6

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-106-6

  • Online ISBN: 978-1-62703-107-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics