Abstract
Moving towards the realization of genomic data in clinical practice, and following an individualized healthcare approach, the function and regulation of genes has to be deciphered and manifested. Two of the most significant forms of molecular data come form microarray gene expression sources, and gene interactions sources – as encoded in Gene Regulatory Networks (GRNs). The usual computational task is the gene selection procedure with the GRNs to be mainly utilized for annotation and enrichment purposes. In this study we present a novel perception of these resources. Initially we locate all functional path-modules encoded in GRNs and we try to assess which of them are compatible and match the gene-expression profiles of samples that belong to different phenotypes. The differential power of the selected path-modules is computed and their biological relevance is assessed. The whole approach was applied on a set of microarray studies with the target of revealing putative regulatory mechanisms that govern and putatively guide the treatment responses of BRCA patients. The results were quite satisfactory according to their biological and clinical relevance.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ideker, T., Galitski, T., Hood, L.: A new approach to decoding life: systems biology. Annual Review of Genomics and Human Genetics 2, 343–372 (2001)
Collins, F.S., Eric, D., Green, E.D., Guttmacher, A.E., Mark, S., Guyer, M.S.: A vision for the future of genomics research. Nature 422, 835–847 (2003)
Simon, R., Radmacher, M.D., Dobbin, K., McShane, L.M.: Pitfalls in the Use of DNA Microarray Data for Diagnostic Classification. Journal of the National Cancer Institute 95(1), 14–18 (2003)
Ambroise, C., McLachlan, G.J.: Selection bias in gene extraction on the basis of microarray gene-expression data. PNAS 99(10), 6562–6566 (2002)
Arkin, A., Ross, J.: Computational functions in biochemical reaction networks. Biophys. J. 67(2), 560–578 (1994)
Kauffman, S.A.: The Origins of Order: Self-Organization and Selection in Evolution. Oxford Univ. Press, New York (1993)
Potamias, G., Koumakis, L., Moustakis, V.: Gene Selection via Discretized Gene-Expression Profiles and Greedy Feature-Elimination. In: Vouros, G.A., Panayiotopoulos, T. (eds.) SETN 2004. LNCS (LNAI), vol. 3025, pp. 256–266. Springer, Heidelberg (2004)
Wang, Y., et al.: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 365(9460), 671–679 (2005)
Sotiriou, C., et al.: Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J. Natl. Cancer Inst. 98(4), 262–272 (2006)
Miller, L.D., et al.: An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. PNAS 102(38), 13550–13555 (2005)
Desmedt, C., et al.: Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin. Cancer Res. 13(11), 3207–3214 (2007)
Sutherland, R.L.: Endocrine resistance in breast cancer: new roles for ErbB3 and ErbB4. Breast Cancer Research 13(3), 106 (2011)
Hutcheson, I.R., et al.: Heregulin beta1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells. Breast Cancer Research 9(4), R50 (2007)
Zhu, Y., Sullivan, L.L., Nair, S.S., Williams, C.C., Pandey, A.K., Marrero, L., Vadlamudi, R.K., Jones, F.E., et al.: Coregulation of estrogen receptor by ERBB4/HER4 establishes a growth-promoting autocrine signal in breast tumor cells. Cancer Research 66(16), 7991–7998 (2006)
Sonne-Hansen, K., et al.: Breast cancer cells can switch between estrogen receptor alpha and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance. Breast Cancer Research and Treatment 121(3), 601–613 (2010)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Koumakis, L., Moustakis, V., Zervakis, M., Kafetzopoulos, D., Potamias, G. (2012). Coupling Regulatory Networks and Microarays: Revealing Molecular Regulations of Breast Cancer Treatment Responses. In: Maglogiannis, I., Plagianakos, V., Vlahavas, I. (eds) Artificial Intelligence: Theories and Applications. SETN 2012. Lecture Notes in Computer Science(), vol 7297. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30448-4_30
Download citation
DOI: https://doi.org/10.1007/978-3-642-30448-4_30
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-30447-7
Online ISBN: 978-3-642-30448-4
eBook Packages: Computer ScienceComputer Science (R0)