Abstract
Plant microRNAs (miRNAs) are short RNA sequences that bind to target mRNAs and change their expression levels by influencing their stabilities and marking them for cleavage. We present a high throughput approach for associating between microRNAs and conditions in which they act, using novel statistical and algorithmic measures. Our new prototype tool, miRNAXpress, computes a (binary) matrix T denoting the potential targets of microRNAs. Then, using T and an additional predefined matrix X indicating expression of genes under various conditions, it produces a new matrix that predicts associations between microRNAs and the conditions in which they act.
The computational intensive part of miRNAXpress is the calculation of T. We provide a hybridization search algorithm which given a query microRNA, a text mRNA, and a predefined energy cutoff threshold, finds and reports all targets (putative binding sites) of the query in the text with binding energy below the predefined threshold. In order to speed it up, we utilize the sparsity of the search space without sacrificing the optimality of the results. Consequently, the time complexity of the search algorithm is almost linear in the size of a sparse set of locations where base-pairs are stacked at a height of three or more.
We employed our tool to conduct a study, using the plant Arabidopsis thaliana as our model organism. By applying miRNAXpress to 98 microRNAs and 380 conditions, some biologically interesting and statistically strong relations were discovered.
Further details, including figures and pseudo-code, can be found at: http://www.cs.technion.ac.il/~michalz/LinearRNA.ps
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Aggarawal, A., Park, J.: Notes on searching in multidimensional monotone arrays. In: Proc. 29th IEEE Symp. on Foundations of Computer Science, pp. 497–512 (1988)
Chatfield, C.: Statistics for technology, a course in applied statistics, Sci. Papreback (1970)
Dugas, D.V., Bartel, B.: MicroRNA regulation of gene expression in plants. Curr. Opin. Plant Biol. 7, 512–520 (2004)
Enright, A.J., et al.: MicroRNA targets in drosophila. Genome Biol. 5(1), 12 (2003)
Eppstein, D., Galil, Z., Giancarlo, R.: Speeding up dynamic programming. In: Proc. 29th IEEE Symp. on Foundations of Computer Science, pp. 488–496 (1988)
Eppstein, D., Galil, Z., Giancarlo, R., Italiano, G.F.: Sparse dynamic programming I: Linear cost functions. JACM 39, 519–545 (1992)
Eppstein, D., Galil, Z., Giancarlo, R., Italiano, G.F.: Sparse dynamic programming II: Concave and convex cost functions. JACM 39, 519–545 (1992)
Galil, Z., Giancarlo, R.: Speeding up dynamic programming with applications to molecular biology. Theoretical Computer Science 64, 107–118 (1989)
Hirshberg, D.S., Larmore, L.L.: The least weight subsequence problem. SIAM J. Compt. 16(4), 628–638 (1987)
Kasschau, K.D., et al.: P1/HC-Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA function. Dev. Cell 4, 205–217 (2003)
Larmore, L., Schieber, B.: On-line dynamic programming with applications to the prediction of RNA secondary structure. J. Algorithms 12(3), 490–515 (1991)
Llave, C., et al.: Cleavage of scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science 23, 2053–2056 (2002)
Mathews, D.H., Sabina, J., Zuker, M., Turner, D.H.: Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288, 911–940 (1999)
Miller, W., Myers, E.: Sequence comparison with concave weighting functions. Bull. of Mathematical Biology 50(2), 97–120 (1988)
Myers, E., Miller, W.: Chaining multiple-alignment fragments in sub-quadratic time. In: ACM-SIAM Symposium on Discrete Algorithms, pp. 1–10 (1995)
Palatnik, J.F., et al.: Control of leaf morphogenesis by microRNAs. Nature 425, 257–263 (2003)
Rajewsky, N., Socci, N.C.: Computational identification of microRNA targets. Genome Biology 5 (2004)
Rehmsmeier, M., Steffen, P., Hochsmann, M., Giegerich, R.: Fast and effective prediction of microRNA/target duplexes. RNA 10, 1507–1517 (2004)
Rhoades, M.W., et al.: Prediction of plant microRNA targets. Cell 23, 513–520 (2002)
Setubal, J., Meidanis, J.: Introduction to computational molecular biology (1997)
Shevchenko, A., et al.: Plant virus infection development as affected by heavy metal stress. Archives of Phytopathology and Plant Protection 23, 139–146 (2004)
Stark, A., et al.: Identification of Drosophila microRNA targets. PLoS. Biol. 1(3) (2003)
Tang, G., et al.: Framework for RNA silencing in plants. Genes Dev. 17, 49–63 (2003)
van Emde Boas, P., Kaas, R., Zijlstra, E.: Design and implementation of an effcient priority queue. Mathematical Systems Theory 10, 99–127 (1977)
Waterman, M.S., Smith, T.F.: Rapid dynamic programming algorithms for RNA secondary structure. Adv. Appl. Math. 7, 455–464 (1986)
Xie, Z., et al.: Negative feedback regulation of dicer-like1 in Arabidopsis by microRNA-guided mRNA degradation. Curr. Biol. 13, 784–789 (2003)
Yekta, S.: MicroRNA-directed cleavage of HOXB8 mRNA. Science 304, 594–596 (2004)
Zuker, M.: Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31(13), 3406–3415 (2003)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Zilberstein, C.BZ., Ziv-Ukelson, M., Pinter, R.Y., Yakhini, Z. (2005). A High-Throughput Approach for Associating microRNAs with Their Activity Conditions. In: Miyano, S., Mesirov, J., Kasif, S., Istrail, S., Pevzner, P.A., Waterman, M. (eds) Research in Computational Molecular Biology. RECOMB 2005. Lecture Notes in Computer Science(), vol 3500. Springer, Berlin, Heidelberg. https://doi.org/10.1007/11415770_11
Download citation
DOI: https://doi.org/10.1007/11415770_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-25866-7
Online ISBN: 978-3-540-31950-4
eBook Packages: Computer ScienceComputer Science (R0)