Abstract
Genome-wide differential expression studies of human diseases using microarray technology usually produce long lists of genes with altered expression, therefore, the genes causally involved in a disease cannot be effectively separated from innocent bystanders. Existing methods for differential analysis of gene expression profiles seem unable to solve this problem successfully. In this paper, we present a systematic strategy that combines gene-wise and function-wise differential analysis of gene expression profiles to interrelate genes and functions with human diseases. The gene-wise analysis adopts a modified T-test to analyze the expression alteration of each single gene, and the alteration is represented by quantitative significant p-value. The function-wise analysis uses a new combined S-test to identify coordinate alterations of genes within each functional category. A computational tool, MageKey, is developed based on this strategy, and its utility is demonstrated by the analysis results of gene expression dataset of human Amyotrophic Lateral Sclerosis disease. MageKey is freely available upon request to authors.
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References
Schena, M., Shalon, D., Davis, R.W., Brown, P.O.: Quantitative Monitoring of Gene Expression Patterns With a Complementary DNA Microarray. Science 270(5235), 467–470 (1995)
Lockhart, D.J., Dong, H., Byrne, M.C., Follettie, M.T., Gallo, M.V., Chee, M.S., Mittmann, M., Wang, C., Kobayashi, M., Horton, H., Brown, E.L.: Expression Monitoring by Hybridization to High-Density Oligonucleotide Arrays. Nat. Biotechnol. 14(13), 1675–1680 (1996)
Schulze, A., Downward, J.: Navigating Gene Expression Using Microarrays–a Technology Review. Nat. Cell Biol. 3(8), E190–E195 (2001)
Young, R.A.: Biomedical Discovery With DNA Arrays. Cell 102(1), 9–15 (2000)
Meltzer, P.S.: Spotting the Target: Microarrays for Disease Gene Discovery. Curr. Opin. Genet. Dev. 11(3), 258–263 (2001)
Lyons, P.A.: Gene-Expression Profiling and the Genetic Dissection of Complex Disease. Curr. Opin. Immunol. 14(5), 627–630 (2002)
Brazma, A., Vilo, J.: Gene Expression Data Analysis. FEBS Lett. 480(1), 17–24 (2000)
Nadon, R., Shoemaker, J.: Statistical Issues With Microarrays: Processing and Analysis. Trends Genet. 18(5), 265–271 (2002)
Leung, Y.F., Cavalieri, D.: Fundamentals of CDNA Microarray Data Analysis. Trends Genet. 19(11), 649–659 (2003)
Miklos, G.L., Maleszka, R.: Microarray Reality Checks in the Context of a Complex Disease. Nat. Biotechnol. 22(5), 615–621 (2004)
Baldi, P., Long, A.D.: A Bayesian Framework for the Analysis of Microarray Expression Eata: Regularized t-Test and Statistical Inferences of Gene Changes. Bioinformatics 17(6), 509–519 (2001)
Tusher, V.G., Tibshirani, R., Chu, G.: Significance Analysis of Microarrays Applied to the Ionizing Radiation Response. Proc. Natl. Acad. Sci. USA 98(9), 5116–5121 (2001)
Wu, T.D.: Analysing Gene Expression Data From DNA Microarrays to Identify Candidate Genes. J. Pathol. 195(1), 53–65 (2001)
Cui, X., Churchill, G.A.: Statistical Tests for Differential Expression in CDNA Microarray Experiments. Genome Biol. 4(4), 210 (2003)
McCarthy, M.I., Smedley, D., Hide, W.: New Methods for Finding Disease-Susceptibility Genes: Impact and Potential. Genome Biol. 4(10), 119 (2003)
Khatri, P., Draghici, S., Ostermeier, G.C., Krawetz, S.A.: Profiling Gene Expression Using Onto-Express. Genomics 79(2), 266–270 (2002)
Draghici, S., Khatri, P., Martins, R.P., Ostermeier, G.C., Krawetz, S.A.: Global Functional Profiling of Gene Expression. Genomics 81(2), 98–104 (2003)
Volinia, S., Evangelisti, R., Francioso, F., Arcelli, D., Carella, M., Gasparini, P.: GOAL: Automated Gene Ontology Analysis of Expression Profiles. Nucleic Acids Res. 32(Web Server issue), W492–W499 (2004)
Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., Hattori, M.: The KEGG Resource for Deciphering the Genome. Nucleic Acids Res. 32(Database issue), D277–D280 (2004)
Harris, M.A., Clark, J., Ireland, A., Lomax, J., Ashburner, M., Foulger, R., Eilbeck, K., Lewis, S., Marshall, B., Mungall, C., Richter, J., Rubin, G.M., Blake, J.A., Bult, C., Dolan, M., Drabkin, H., Eppig, J.T., Hill, D.P., Ni, L., Ringwald, M., Balakrishnan, R., Cherry, J.M., Christie, K.R., Costanzo, M.C., Dwight, S.S., Engel, S., Fisk, D.G., Hirschman, J.E., Hong, E.L., Nash, R.S., Sethuraman, A., Theesfeld, C.L., Botstein, D., Dolinski, K., Feierbach, B., Berardini, T., Mundodi, S., Rhee, S.Y., Apweiler, R., Barrell, D., Camon, E., Dimmer, E., Lee, V., Chisholm, R., Gaudet, P., Kibbe, W., Kishore, R., Schwarz, E.M., Sternberg, P., Gwinn, M., Hannick, L., Wortman, J., Berriman, M., Wood, V., de la, C.N., Tonellato, P., Jaiswal, P., Seigfried, T., White, R.: The Gene Ontology (GO) Database and Informatics Resource. Nucleic Acids Res. 32(Database issue), D258–D261 (2004)
Pruitt, K.D., Maglott, D.R.: RefSeq and LocusLink: NCBI Gene-Centered Resources. Nucleic Acids Res. 29(1), 137–140 (2001)
Edgar, R., Domrachev, M., Lash, A.E.: Gene Expression Omnibus: NCBI Gene Expression and Hybridization Array Data Repository. Nucleic Acids Res. 30(1), 207–210 (2002)
Liu, G., Loraine, A.E., Shigeta, R., Cline, M., Cheng, J., Valmeekam, V., Sun, S., Kulp, D., Siani-Rose, M.A.: NetAffx: Affymetrix Probesets and Annotations. Nucleic Acids Res. 31(1), 82–86 (2003)
Malaspina, A., de Belleroche, J.: Spinal Cord Molecular Profiling Provides a Better Understanding of Amyotrophic Lateral Sclerosis Pathogenesis. Brain Res. Rev. 45(3), 213–229 (2004)
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Wang, W., Zhou, Y., Bi, R. (2005). Correlating Genes and Functions to Human Disease by Systematic Differential Analysis of Expression Profiles. In: Huang, DS., Zhang, XP., Huang, GB. (eds) Advances in Intelligent Computing. ICIC 2005. Lecture Notes in Computer Science, vol 3645. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11538356_2
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DOI: https://doi.org/10.1007/11538356_2
Publisher Name: Springer, Berlin, Heidelberg
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