Probe Selection for Pathway-Specific Microarray Probe Design Minimizing Melting Temperature Variance
In molecular biology, microarray technology is widely and successfully utilized to efficiently measure gene activity. If working with less studied organisms, methods to design custom-made microarray probes are available. One design criterion is to select probes with minimal melting temperature variances thus ensuring similar hybridization properties. If the microarray application focuses on the investigation of metabolic pathways, it is not necessary to cover the whole genome. It is more efficient to cover each metabolic pathway with a limited number of genes. Firstly, an approach is presented which minimizes the overall melting temperature variance of selected probes for all genes of interest. Secondly, the approach is extended to include the additional constraints of covering all pathways with a limited number of genes while minimizing the overall variance. The new optimization problem is solved by a bottom-up programming approach which reduces the complexity to make it computationally feasible. The new method is exemplary applied for the selection of microarray probes in order to cover all fungal secondary metabolite gene clusters for Aspergillus terreus.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1332236Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF
 P. A. Jensen and J. A. Papin, "Functional integration of a metabolic network model and expression data without arbitrary thresholding." Bioinformatics, vol. 27, no. 4, pp. 541-547, Feb 2011. (Online). Available: http://dx.doi.org/10.1093/bioinformatics/btq702
 J.-M. Schwartz, C. Gaugain, J. C. Nacher, A. de Daruvar, and M. Kanehisa, "Observing metabolic functions at the genome scale." Genome Biol, vol. 8, no. 6, p. R123, 2007. (Online). Available: http://dx.doi.org/10.1186/gb-2007-8-6-r123
 S. Lemoine, F. Combes, and S. L. Crom, "An evaluation of custom microarray applications: the oligonucleotide design challenge." Nucleic Acids Res, vol. 37, no. 6, pp. 1726-1739, Apr 2009. (Online). Available: http://dx.doi.org/10.1093/nar/gkp053
 J. SantaLucia and D. H. Turner, "Measuring the thermodynamics of RNA secondary structure formation." Biopolymers, vol. 44, no. 3, pp. 309-319, 1997. (Online). Available: http://dx.doi.org/3.0.CO;2-Z
 N. L. Nov`ere, "MELTING, computing the melting temperature of nucleic acid duplex." Bioinformatics, vol. 17, no. 12, pp. 1226-1227, Dec 2001.
 S. Graf, F. G. G. Nielsen, S. Kurtz, M. A. Huynen, E. Birney, H. Stunnenberg, and P. Flicek, "Optimized design and assessment of whole genome tiling arrays." Bioinformatics, vol. 23, no. 13, pp. i195-i204, Jul 2007. (Online). Available: http://dx.doi.org/10.1093/ bioinformatics/btm200
 L. Jourdren, A. Duclos, C. Brion, T. Portnoy, H. Mathis, A. Margeot, and S. L. Crom, "Teolenn: an efficient and customizable workflow to design high-quality probes for microarray experiments." Nucleic Acids Res, vol. 38, no. 10, p. e117, Jun 2010. (Online). Available: http://dx.doi.org/10.1093/nar/gkq110
 F. Horn, H.-W. Nutzmann, V. Schroeckh, R. Guthke, and C. Hummert, "Optimization of a microarray probe design focusing on the minimization of cross-hybridization," in Proceedings of the International Conference on Bioinformatics and Computational Biology (BIOCOMP-11), H. R. Arabnia and Quoc-Nam, Eds., 2011, ISBN: 1-60132-172-4.
 H.-W. Nutzmann, Y. Reyes-Dominguez, K. Scherlach, V. Schroeckh, F. Horn, A. Gacek, J. Schumann, C. Hertweck, J. Strauss, and A. A. Brakhage, "Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation." Proc Natl Acad Sci U S A, vol. 108, no. 34, pp. 14 282-14 287, Aug 2011. (Online). Available: http://dx.doi.org/10.1073/pnas.1103523108
 F. Bidard, S. Imbeaud, N. Reymond, O. Lespinet, P. Silar, C. Clav'e, H. Delacroix, V. Berteaux-Lecellier, and R. Debuchy, "A general framework for optimization of probes for gene expression microarray and its application to the fungus Podospora anserina." BMC Res Notes, vol. 3, p. 171, 2010. (Online). Available: http://dx.doi.org/10.1186/1756-0500-3-171
 R. Wernersson and H. B. Nielsen, "OligoWiz 2.0-integrating sequence feature annotation into the design of microarray probes." Nucleic Acids Res, vol. 33, no. Web Server issue, pp. W611-W615, Jul 2005. (Online). Available: http://dx.doi.org/10.1093/nar/gki399
 A. A. Brakhage and V. Schroeckh, "Fungal secondary metabolites - strategies to activate silent gene clusters." Fungal Genet Biol, vol. 48, no. 1, pp. 15-22, Jan 2011. (Online). Available: http: //dx.doi.org/10.1016/j.fgb.2010.04.004
 N. Khaldi, F. T. Seifuddin, G. Turner, D. Haft, W. C. Nierman, K. H. Wolfe, and N. D. Fedorova, "SMURF: Genomic mapping of fungal secondary metabolite clusters." Fungal Genet Biol, vol. 47, no. 9, pp. 736-741, Sep 2010. (Online). Available: http://dx.doi.org/10.1016/j.fgb.2010.06.003
 G. Bhanot, Y. Louzoun, J. Zhu, and C. DeLisi, "The importance of thermodynamic equilibrium for high throughput gene expression arrays." Biophys J, vol. 84, no. 1, pp. 124-135, Jan 2003. (Online). Available: http://dx.doi.org/10.1016/S0006-3495(03)74837-1