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Gene Expression Networks

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Computational Toxicology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 930))

Abstract

With the advent of microarrays and next-generation biotechnologies, the use of gene expression data has become ubiquitous in biological research. One potential drawback of these data is that they are very rich in features or genes though cost considerations allow for the use of only relatively small sample sizes. A useful way of getting at biologically meaningful interpretations of the environmental or toxicological condition of interest would be to make inferences at the level of a priori defined biochemical pathways or networks of interacting genes or proteins that are known to perform certain biological functions. This chapter describes approaches taken in the literature to make such inferences at the biochemical pathway level. In addition this chapter describes approaches to create hypotheses on genes playing important roles in response to a treatment, using organism level gene coexpression or protein–protein interaction networks. Also, approaches to reverse engineer gene networks or methods that seek to identify novel interactions between genes are described. Given the relatively small sample numbers typically available, these reverse engineering approaches are generally useful in inferring interactions only among a relatively small or an order 10 number of genes. Finally, given the vast amounts of publicly available gene expression data from different sources, this chapter summarizes the important sources of these data and characteristics of these sources or databases. In line with the overall aims of this book of providing practical knowledge to a researcher interested in analyzing gene expression data from a network perspective, the chapter provides convenient publicly accessible tools for performing analyses described, and in addition describe three motivating examples taken from the published literature that illustrate some of the relevant analyses.

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References

  1. Crick F (1970) Central dogma of molecular biology. Nature 227(5258):561–563

    Article  PubMed  CAS  Google Scholar 

  2. Greenbaum D et al (2003) Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol 4(9):117

    Article  PubMed  Google Scholar 

  3. Barrett T, Edgar R (2006) Gene expression omnibus: microarray data storage, submission, retrieval, and analysis. DNA Microarrays, Part B: Databases Stat 411:352–369

    Article  CAS  Google Scholar 

  4. Parkinson H et al (2009) ArrayExpress update—from an archive of functional genomics experiments to the atlas of gene expression. Nucleic Acids Res 37(Suppl 1):D868

    Article  PubMed  CAS  Google Scholar 

  5. Brazma A et al (2001) Minimum information about a microarray experiment (MIAME)—toward standards for microarray data. Nat Genet 29(4):365–371

    Article  PubMed  CAS  Google Scholar 

  6. Von Mering C et al (2006) STRING 7—recent developments in the integration and prediction of protein interactions. Nucleic Acids Res 35(Suppl 1):D358

    Google Scholar 

  7. Gentleman RC et al (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5(10):R80

    Article  PubMed  Google Scholar 

  8. Team RDC (2009) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

    Google Scholar 

  9. Crawley MJ (2005) Statistics: an introduction using R. Wiley, Chichester

    Book  Google Scholar 

  10. Shannon P et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498

    Article  PubMed  CAS  Google Scholar 

  11. Zhu Y et al (2008) GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus. Bioinformatics 24(23):2798

    Article  PubMed  CAS  Google Scholar 

  12. Davis S, Meltzer PS (2007) GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics 23(14):1846

    Article  PubMed  Google Scholar 

  13. Kauffmann A et al (2009) Importing arrayexpress datasets into r/bioconductor. Bioinformatics 25(16):2092

    Article  PubMed  CAS  Google Scholar 

  14. Widenius M, Axmark D, DuBois P (2002) MySQL reference manual. O’Reilly & Associates, Inc., Sebastopol, CA

    Google Scholar 

  15. Ashburner M et al (2000) Gene ontology: tool for the unification of biology. Nat Genet 25(1):25

    Article  PubMed  CAS  Google Scholar 

  16. Al-Shahrour F, DĂ­az-Uriarte R, Dopazo J (2004) FatiGO: a web tool for finding significant associations of gene ontology terms with groups of genes. Bioinformatics 20(4):578

    Article  PubMed  CAS  Google Scholar 

  17. BeiĂźbarth T, Speed TP (2004) GOstat: find statistically overrepresented gene ontologies within a group of genes. Bioinformatics 20(9):1464

    Article  PubMed  Google Scholar 

  18. Subramanian A et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102(43):15545

    Article  PubMed  CAS  Google Scholar 

  19. Thomas R et al (2009) Choosing the right path: enhancement of biologically relevant sets of genes or proteins using pathway structure. Genome Biol 10(4):R44

    Article  PubMed  Google Scholar 

  20. Goeman JJ, BĂĽhlmann P (2007) Analyzing gene expression data in terms of gene sets: methodological issues. Bioinformatics 23(8):980

    Article  PubMed  CAS  Google Scholar 

  21. Alexa A, RahnenfĂĽhrer J, Lengauer T (2006) Improved scoring of functional groups from gene expression data by decorrelating GO graph structure. Bioinformatics 22(13):1600

    Article  PubMed  CAS  Google Scholar 

  22. Da Wei Huang BTS, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  Google Scholar 

  23. Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1

    Article  Google Scholar 

  24. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 98(9):5116

    Article  PubMed  CAS  Google Scholar 

  25. Kanehisa M et al (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36(Suppl 1):D480

    PubMed  CAS  Google Scholar 

  26. Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27

    Article  PubMed  CAS  Google Scholar 

  27. Kanehisa M et al (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 34(Database Issue):D354

    Article  PubMed  CAS  Google Scholar 

  28. Subramanian A et al (2007) GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics 23(23):3251

    Article  PubMed  CAS  Google Scholar 

  29. Enright AJ, Van Dongen S, Ouzounis CA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30(7):1575

    Article  PubMed  CAS  Google Scholar 

  30. Akutsu T, Miyano S, Kuhara S (2000) Inferring qualitative relations in genetic networks and metabolic pathways. Bioinformatics 16(8):727

    Article  PubMed  CAS  Google Scholar 

  31. Bernardo D, Gardner T, Collins JJ (2004) Robust identification of large genetic networks

    Google Scholar 

  32. Chen T, He HL, Church GM (1999) Modeling gene expression with differential equations. Pac Symp Biocomput 4:29–40

    Google Scholar 

  33. D’haeseleer P, Liang S, Somogyi R (2000) Genetic network inference: from co-expression clustering to reverse engineering. Bioinformatics 16(8):707

    Article  PubMed  Google Scholar 

  34. Ideker TE, Thorsson V, Karp RM (2000) Discovery of regulatory interactions through perturbation: inference and experimental design. Pac Symp Biocomput 5:302–313

    Google Scholar 

  35. Margolin A et al (2006) ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinform 7(Suppl 1):S7

    Article  Google Scholar 

  36. Hartemink AJ et al (2002) Bayesian methods for elucidating genetic regulatory networks. IEEE Intell Syst 17:37–43

    Google Scholar 

  37. Yamanaka T et al (2004) The TAO-Gen algorithm for identifying gene interaction networks with application to SOS repair in E. coli. Environ Health Perspect 112(16):1614

    Article  PubMed  CAS  Google Scholar 

  38. Thomas R et al (2004) A model-based optimization framework for the inference of gene regulatory networks from DNA array data. Bioinformatics 20(17):3221–3235

    Article  PubMed  CAS  Google Scholar 

  39. Thomas R et al (2007) A model-based optimization framework for the inference of regulatory interactions using time-course DNA microarray expression data. BMC Bioinform 8(1):228

    Article  Google Scholar 

  40. Dasika M et al (2003) A mixed integer linear programming (MILP) framework for inferring time delay in gene regulatory networks. World Scientific Pub Co Inc.

    Google Scholar 

  41. Sales G, Romualdi C (2011) Parmigene—a parallel R package for mutual information estimation and gene network reconstruction. Bioinformatics 27:1876–1877

    Article  PubMed  CAS  Google Scholar 

  42. McHale C et al (2010) Global gene expression profiling of a population exposed to a range of benzene levels. Environ Health Perspect 10

    Google Scholar 

  43. Auerbach SS et al (2010) Comparative phenotypic assessment of cardiac pathology, physiology, and gene expression in C3H/HeJ, C57BL/6J, and B6C3F1/J mice. Toxicol Pathol 38(6):923

    Article  PubMed  CAS  Google Scholar 

  44. Jupiter D, Chen H, VanBuren V (2009) STARNET 2: a web-based tool for accelerating discovery of gene regulatory networks using microarray co-expression data. BMC Bioinform 10(1):332

    Article  Google Scholar 

  45. Toyoshiba H et al (2006) Gene interaction network analysis suggests differences between high and low doses of acetaminophen. Toxicol Appl Pharmacol 215(3):306–316

    Article  PubMed  CAS  Google Scholar 

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The findings and conclusions in this report are those of the authors and do not necessarily represent the views and positions of the Centers for Disease Control and Prevention or the Agency for Toxic Substances and Disease Registry.

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Correspondence to Christopher J. Portier .

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Thomas, R., Portier, C.J. (2013). Gene Expression Networks. In: Reisfeld, B., Mayeno, A. (eds) Computational Toxicology. Methods in Molecular Biology, vol 930. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-059-5_7

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  • DOI: https://doi.org/10.1007/978-1-62703-059-5_7

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-058-8

  • Online ISBN: 978-1-62703-059-5

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