Skip to main content

Identification of the Minimal Connected Network of Transcription Factors by Transcriptomic and Genomic Data Integration

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1164))

Abstract

Thanks to high-throughput experiments, biological conditions can be investigated at both the entire genomic and transcriptomic levels. In addition, protein–protein interaction (PPI) data are widely available for well-studied organisms, such as human. In this chapter, we will present an integrative approach that makes use of these data to find the PPI module involving the key regulated transcription factors shared by a number of given conditions. These conditions could be for instance different cancer types. Briefly, for the studied conditions, we need to identify commonly affected chromosomal regions subjected to copy number alterations together with the identification of differentially expressed list of genes in each condition. Transcription factor activity will be inferred from these regulated gene lists. Then, we will define TFs, for which the activity could be explained by an associative effect of both loci copy number alteration and gene expression levels of their coding genes. PPI networks could be mined, afterwards, using appropriate algorithms to find the significant module that connect those TFs together. This module could be viewed as the minimal connected network of TFs, the regulation of which is shared between the investigated conditions.

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

Buying options

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

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Keshava Prasad TS, Goel R, Kandasamy K et al (2009) Human protein reference database – 2009 update. Nucleic Acids Res 37:D767–D772

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Portales-Casamar E, Arenillas D, Lim J et al (2009) The PAZAR database of gene regulatory information coupled to the ORCA toolkit for the study of regulatory sequences. Nucleic Acids Res 37:D54–D60

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Boyle AP, Hong EL, Hariharan M et al (2012) Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 22:1790–1797

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Aerts S, Haeussler M, van Vooren S et al (2008) Text-mining assisted regulatory annotation. Genome Biol 9:R31

    Article  PubMed Central  PubMed  Google Scholar 

  5. Essaghir A, Toffalini F, Knoops L et al (2010) Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data. Nucleic Acids Res 38:e120

    Article  PubMed Central  PubMed  Google Scholar 

  6. Essaghir A, Demoulin J-B (2012) A minimal connected network of transcription factors regulated in human tumors and its application to the quest for universal cancer biomarkers. PLoS One 7:e39666

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bioconductor – About. http://www.bioconductor.org/about/

  8. Lim WK, Wang K, Lefebvre C et al (2007) Comparative analysis of microarray normalization procedures: effects on reverse engineering gene networks. Bioinformatics 23:i282–288

    Article  CAS  PubMed  Google Scholar 

  9. An open-source R framework for your microarray analysis | aroma-project.org, http://www.aroma-project.org/

  10. Smyth G (2005) Limma: linear models for microarray data. In: Gentleman R, Carey V, Dudoit S et al (eds) Bioinformatics and computational biology solutions using R and bioconductor. Springer, New York, pp 397–420

    Chapter  Google Scholar 

  11. Montano-Almendras CP, Essaghir A, Schoemans H et al (2012) ETV6-PDGFRB and FIP1L1-PDGFRA stimulate human hematopoietic progenitor cell proliferation and differentiation into eosinophils: the role of nuclear factor-κB. Haematologica 97:1064–1072

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Pachikian BD, Essaghir A, Demoulin J-B et al (2012) Prebiotic approach alleviates hepatic steatosis: implication of fatty acid oxidative and cholesterol synthesis pathways. Mol Nutr Food Res 57(2):347–359

    Article  PubMed  Google Scholar 

  13. Pachikian BD, Essaghir A, Demoulin J-B et al (2011) Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. PLoS One 6:e23365

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Beroukhim R, Getz G, Nghiemphu L et al (2007) Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci U S A 104:20007–20012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Hupé P, Stransky N, Thiery J-P et al (2004) Analysis of array CGH data: from signal ratio to gain and loss of DNA regions. Bioinformatics 20:3413–3422, Oxford

    Article  PubMed  Google Scholar 

  16. Bengtsson H, Wirapati P, Speed TP (2009) A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6. Bioinformatics 25:2149–2156, Oxford

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Medina I, Carbonell J, Pulido L et al (2010) Babelomics: an integrative platform for the analysis of transcriptomics, proteomics and genomic data with advanced functional profiling. Nucleic Acids Res 38:W210–W213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Saito R, Smoot ME, Ono K et al (2012) A travel guide to cytoscape plugins. Nat Methods 9:1069–1076

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ahmed Essaghir .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Essaghir, A. (2014). Identification of the Minimal Connected Network of Transcription Factors by Transcriptomic and Genomic Data Integration. In: Miyamoto-Sato, E., Ohashi, H., Sasaki, H., Nishikawa, Ji., Yanagawa, H. (eds) Transcription Factor Regulatory Networks. Methods in Molecular Biology, vol 1164. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0805-9_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0805-9_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0804-2

  • Online ISBN: 978-1-4939-0805-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics