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Constructing Probabilistic Genetic Networks of Plasmodium falciparum from Dynamical Expression Signals of the Intraerythrocytic Development Cycle

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Methods of Microarray Data Analysis V

Abstract

The completion of the genome sequence of Plasmodium falciparum revealed that close to 60% of the annotated genome corresponds to hypothetical proteins and that many genes, whose metabolic pathways or biological products are known, have not been predicted from sequence similarity searches. Recently, using global gene expression of the asexual blood stages of P. falciparum at 1 h resolution scale and Discrete Fourier Transform based techniques, it has been demonstrated that many genes are regulated in a single periodic manner during the asexual blood stages. Moreover, by ordering the genes according to the phase of expression, a new list of targets for vaccine and drug development was generated. In the present paper, genes are annotated under a different perspective: a list of functional properties is attributed to networks of genes representing subsystems of the P. falciparum regulatory expression system. The model developed to represent genetic networks, called Probabilistic Genetic Network (PGN), is a Markov chain with some additional properties. This model mimics the properties of a gene as a non-linear stochastic gate and the systems are built by coupling of these gates. Moreover, a tool that integrates mining of dynamical expression signals by PGN design techniques, different databases and biological knowledge, was developed. The applicability of this tool for discovering gene networks of the malaria expression regulation system has been validated using the glycolytic pathway as a “gold-standard”, as well as by creating an apicoplast PGN network. Presently, we are tentatively improving the network design technique before trying to validate results from the apicoplast PGN network through reverse genetics approaches.

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References

  1. Bozdech, Z., Llinas, M., Pulliam, B.L., Wong, E.D., Zhu, J., and DeRisi, J.L., The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum, PLoS Biol., 1 (2003), 5.

    Article  Google Scholar 

  2. Calderwood, M.S., Gannoun-Zaki, L., Wellems, T.E., and Deitsch, K.W., Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron, J. Biol. Chem., 278(36) (2003), 34125–34132.

    Article  PubMed  CAS  Google Scholar 

  3. Coulson, R.M., Hall, N., and Ouzounis, C.A., Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum, Genome Res., 14 (2004), 1548–1554.

    Article  PubMed  CAS  Google Scholar 

  4. Daily, J.P., Le Roch, K.G., Sarr, O., Fang, X., Zhou, Y., Ndir, O., Mboup, S., Sultan, A., Winzeler, E.A., and Wirth, D.F., In vivo transcriptional profiling of Plasmodium falciparum, Malar J., 3 (2004), 30.

    Article  PubMed  Google Scholar 

  5. DeGroot, M.H., Uncertainty, information and sequential experiments, Ann. Math. Statist., 3 (1962), 404–419.

    Google Scholar 

  6. Dougherty, E.R., Bittner, M.L., Chen, Y., Kim, S., Sivakumar, K., Barrera, J., Meltzer, P., and Trent, J.M., In: Proceedings of Nonlinear Filters in Genomic Control IEEE-EURASI Workshop on Nonlinear Signal and Image Processing (Antalia, Turkey, 1999), pp. 10–15.

    Google Scholar 

  7. Florens, L., Washburn, M.P., Raine, J.D., Anthony, R.M., Grainger, M., Haynes, J.D., Moch, J.K., Muster, N., Sacci, J.B., Tabb, D.L., Witney, A.A., Wolters, D., Wu, Y., Gardner, M.J., Holder, A.A., Sinden, R.E., Yates, J.R., and Carucci, D.J., A proteomic view of the Plasmodium falciparum life cycle, Nature, 419 (2002), 520–526.

    Article  PubMed  CAS  Google Scholar 

  8. Foth, B.J., Ralph, S.A., Tonkin, C.J., Struck, N.S., Fraunholz, M., Roos, D.S., Cowman, A.F., and McFadden, G.I., Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum, Science, 299 (2003), 705–708.

    Article  PubMed  CAS  Google Scholar 

  9. Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R.W., Carlton, J.M., Pain, A., Nelson, K.E., Bowman, S., Paulsen, I.T., James, K., Eisen, J.A., Rutherford, K., Salzberg, S.L., Craig, A., Kyes, S., Chan, M.S., Nene, V., Shallom, S.J., Suh, B., Peterson, J., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., Haft, D., Mather, M.W., Vaidya, A.B., Martin, D.M., Fairlamb, A.H., Fraunholz, M.J., Roos, D.S., Ralph, S.A., McFadden, G.I., Cummings, L.M., Subramanian, G.M., Mungall, C., Venter, J.C., Carucci, D.J., Hoffman, S.L., Newbold, C., Davis, R.W., Fraser, C.M., and Barrell, B., Genome sequence of the human malaria parasite Plasmodium falciparum, Nature, 419 (2002), 498–511.

    Article  PubMed  CAS  Google Scholar 

  10. Hall, N., Karras, M., Raine, J.D., Carlton, J.M., Kooij, T.W., Berriman, M., Florens, L., Janssen, C.S., Pain, A., Christophides, G.K., James, K., Rutherford, K., Harris, B., Harris, D., Churcher, C., Quail, M.A., Ormond, D., Doggett, J., Trueman, H.E., Mendoza, J., Bidwell, S.L., Rajandream, M.A., Carucci, D.J., Yates III, J.R., Kafatos, F.C., Janse, C.J., Barrell, B., Turner, C.M., Waters, A.P., and Sinden, R.E., A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic and proteomic analyses, Science, 307 (2005), 82–86.

    Article  PubMed  CAS  Google Scholar 

  11. Hashimoto, R.F., Kim, S., Shmulevich, I., Zhang, W., Bittner, M.L., and Dougherty, E.R., Growing genetic regulatory networks from seed genes, Bioinformatics, 20 (2004), 1241–1247.

    Article  PubMed  CAS  Google Scholar 

  12. Hayward, R.E., Derisi, J.L., Alfadhli, S., Kaslow, D.C., Brown, P.O., and Rathod, P.K., Shotgun DNA microarrays and stage-specific gene expression in Plasmodium falciparum malaria, Mol. Microbiol., 35 (2000), 6–14.

    Article  PubMed  CAS  Google Scholar 

  13. Horrocks, P., Dechering, K., and Lanzer, M., Control of gene expression in Plasmodium falciparum, Mol. Biochem. Parasitol., 95 (1998), 171–181.

    Article  PubMed  CAS  Google Scholar 

  14. Lasonder, E., Ishihama, Y., Andersen, J.S., Vermunt, A.M., Pain, A., Sauerwein, R.W., Eling, W.M., Hall, N., Waters, A.P., Stunnenberg, H.G., and Mann, M., Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry, Nature, 419 (2002), 537–542.

    Article  PubMed  CAS  Google Scholar 

  15. Le Roch, K.G., Johnson, J.R., Florens, L., Zhou, Y., Santrosyan, A., Grainger, M., Yan, S.F., Williamson, K.C., Holder, A.A., Carucci, D.J., Yates, J.R., III, and Winzeler, E.A., Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle, Genome Res., 14 (2004), 2308–2318.

    Article  PubMed  Google Scholar 

  16. Le Roch, K.G., Zhou, Y., Blair, P.L., Grainger, M., Moch, J.K., Haynes, J.D., De La Vega, P., Holder, A.A., Batalov, S., Carucci, D.J., and Winzeler, E.A., Discovery of gene function by expression profiling of the malaria parasite life cycle, Science, 301 (2003), 1503–1508.

    Article  PubMed  Google Scholar 

  17. Patankar, S., Munasinghe, A., Shoaibi, A., Cummings, L.M., and Wirth, D.F., Serial analysis of gene expression in Plasmodium falciparum reveals the global expression profile of erythrocytic stages and the presence of anti-sense transcripts in the malarial parasite, Mol. Biol. Cell., 12 (2001), 3114–3125.

    PubMed  CAS  Google Scholar 

  18. Quackenbush, J., Microarray data normalization and transformation, Nat. Genetics, 32 (2002), 496–501.

    Article  CAS  Google Scholar 

  19. Ralph, S.A., Van Dooren, G.G., Waller, R.F., Crawford, M.J., Fraunholz, M.J., Foth, B.J., Tonkin, C.J., Roos, D.S., and McFadden, G.I., Metabolic maps and functions of the Plasmodium falciparum apicoplast, Nat. Rev. Microbiol., 2 (2004), 203–216.

    Article  PubMed  CAS  Google Scholar 

  20. Shimulevich, I., Dougherty, E.R., Kim, S., and Zhang, W., Probabilistic Boolean networks: A rule-based uncertainty model for gene regulatory networks, Bioinformatics, 18(2) (2002), 261–274.

    Article  Google Scholar 

  21. Sherman, I.W., Metabolism and surface transport of parasitized erythrocytes in malaria, Ciba Found Symp., 94 (1983), 206–221.

    PubMed  CAS  Google Scholar 

  22. Wilson, R.J.M. (Iain), Progress with parasite plastids, J. Mol. Biol., 319 (2002), 257–274.

    Google Scholar 

  23. Yeh, I., Hanekamp, T., Tsoka, S., Karp, P.D., and Altman, R.B., Computational analysis of Plasmodium falciparum metabolism: Organizing genomic information to facilitate drug discovery, Genome Res., 14 (2004), 917–924.

    Article  PubMed  CAS  Google Scholar 

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Barrera, J. et al. (2007). Constructing Probabilistic Genetic Networks of Plasmodium falciparum from Dynamical Expression Signals of the Intraerythrocytic Development Cycle. In: McConnell, P., Lin, S.M., Hurban, P. (eds) Methods of Microarray Data Analysis V. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-34569-7_2

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