Abstract
Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunosuppressed patients. During the infection process, A. fumigatus has to cope with a dramatic change of environmental conditions, such as temperature shifts. Recently, gene expression data monitoring the stress response to a temperature shift from 30 °C to 48 °C was published. In the present work, these data were analyzed by reverse engineering to discover gene regulatory mechanisms of temperature resistance of A. fumigatus. Time series data, i.e. expression profiles of 1926 differentially expressed genes, were clustered by fuzzy c-means. The number of clusters was optimized using a set of optimization criteria. From each cluster a representative gene was selected by text mining in the gene descriptions and evaluating gene ontology terms. The expression profiles of these genes were simulated by a differential equation system, whose structure and parameters were optimized minimizing both the number of non-vanishing parameters and the mean square error of model fit to the microarray data.
This is a preview of subscription content, log in via an institution to check access.
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
Brakhage, A.A., Langfelder, K.: The molecular biology of Aspergillus fumigatus. Annual Review of Microbiol 56, 433–455 (2002)
Nierman, W.C., et al.: Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438, 1151–1156 (2005)
Ouyang, M., Welsh, W.J., Georgopoulos, P.: Gaussian mixture clustering and imputation of microarray data. Bioinformatics 20, 917–923 (2004)
Troyanskaya, O., et al.: Missing values methods for DNA microarrays. Bioinformatics 17, 520–525 (2001)
Hathaway, R.J., Hu, Y., Bezdek, J.C.: Local Convergence of Tri-Level Alternating Optimization. Neural Parallel Sci. Comput. 9, 19–28 (2001)
Timm, H.: Fuzzy-Clusteranalyse: Methoden zur Exploration von Daten mit fehlenden Werten sowie klassifizierten Daten, Dissertation, University of Magdeburg, Germany (2002), http://fuzzy.cs.uni-magdeburg.de/~htimm/data/dissertation.pdf
Bezdek, J.C., Pal, S.K.: Fuzzy models for pattern recognition: methods that search for structures in data. IEEE Press, New York (1992)
Bezdek, J.C., Pal, N.R.: Some new indexes of cluster validity. IEEE Trans. Syst. Man Cybern. B28, 301–315 (1998)
Bolshakova, N., Azuaje, F.: Cluster validation techniques for genome expression data. Signal Process. 83, 825–833 (2003)
Möller, U., Radke, D.: A cluster validity approach based on nearest neighbor resampling. In: International Conference on Pattern Recognition, Hong Kong, August (2006)
Yeung, M.K., Tegner, J., Collins, J.J.: Reverse engineering gene networks using singular value decomposition and robust regression. Proc. Natl. Acad. Sci. USA 99, 6163–6168 (2002)
Guthke, R., et al.: Dynamic network reconstruction from gene expression data applied to immune response during bacterial infection. Bioinformatics 21, 1626–1634 (2005)
Paris, S., et al.: Catalases of Aspergillus fumigatus. Infect Immun. 71, 3551–3562 (2003)
Mellado, E., et al.: Targeted gene disruption of the 14-alpha sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility. Antimicrob Agents Chemother. 49, 2536–2538 (2005)
Imazu, H., Sakurai, H.: Saccharomyces cerevisiae heat shock transcription factor regulates cell wall remodeling in response to heat shock. Eukaryot. Cell 4, 1050–1056 (2005)
Brakhage, A.A.: Systemic fungal infections caused by Aspergillus species: epidemiology, infection process and virulence determinants. Curr. Drug Targets 6, 875–886 (2005)
Beney, L., Gervais, P.: Influence of the fluidity of the membrane on the response of microorganisms to environmental stress. Appl. Microbiol. Biotechnol. 57, 34–42 (2001)
Ferreira, M.E., et al.: The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus. Med. Mycol. 43(Suppl. 1), S313–S319 (2005)
Swan, T.M., Watson, K.: Stress tolerance in a yeast sterol auxotroph: role of ergosterol, heat shock proteins and trehalose. FEMS Microbiol. Lett. 169, 191–197 (1998)
Dahl, C., Biemann, H.-P., Dahl, J.: A protein kinase antigenically related to pp60v-src possibly involved in yeast cell cycle control: Positive in vivo regulation by sterol. Proc. Natl. Acad. Sci. USA 84, 4012–4016 (1987)
Bhabra, R., Askew, D.S.: Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med. Mycol. 43, S87–S93 (2005)
Burnie, J.P., et al.: Fungal heat-shock proteins in human disease. FEMS Microbiol. Rev. 30, 53–88 (2006)
Author information
Authors and Affiliations
Editor information
Rights and permissions
Copyright information
© 2007 Springer Berlin Heidelberg
About this paper
Cite this paper
Guthke, R., Kniemeyer, O., Albrecht, D., Brakhage, A.A., Möller, U. (2007). Discovery of Gene Regulatory Networks in Aspergillus fumigatus . In: Tuyls, K., Westra, R., Saeys, Y., Nowé, A. (eds) Knowledge Discovery and Emergent Complexity in Bioinformatics. KDECB 2006. Lecture Notes in Computer Science(), vol 4366. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71037-0_3
Download citation
DOI: https://doi.org/10.1007/978-3-540-71037-0_3
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-71036-3
Online ISBN: 978-3-540-71037-0
eBook Packages: Computer ScienceComputer Science (R0)