MicroRNAs (miRNAs) are short (~21 nt) nucleotide sequences that are either co-transcribed during the production of mRNA or are organized in intergenic regions transcribed by RNA polymerase II. In animals, Drosha, and in plants DCL1 recognize pre-miRNAs which set themselves apart by their characteristic stem loop (hairpin) structure. This structure appears important for their recognition during the process of maturation leading to functioning mature miRNAs. A large body of research is available for computational pre-miRNA detection in animals, but less within the plant kingdom. For the prediction of pre-miRNAs, usually machine learning approaches are employed. Therefore, it is necessary to convert the pre-miRNAs into a set of features that can be calculated and many such features have been described. We here select a subset of the previously described features and add sequence motifs as new features. The resulting model which we called MotifmiRNAPred was tested on known pre-miRNAs listed in miRBase and its accuracy was compared to existing approaches in the field. With an accuracy of 99.95% for the generalized plant model, it distinguishes itself from previously published results which reach an average accuracy between 74% and 98%. We believe that our approach is useful for prediction of pre-miRNAs in plants without per species adjustment.
Erson-Bensan, A.E. (2014) Introduction to microRNAs in Biological Systems. Methods in Molecular Biology, 1107, 1-14. http://www.ncbi.nlm.nih.gov/pubmed/24272428
Allmer, J. and Yousef, M. (2012) Computational Methods for ab Initio Detection of microRNAs. Frontiers in Genetics. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3467617&tool=pmcentrez&rendertype= abstract
Lee, R.C., Feinbaum, R.L. and Ambros, V. (1993) The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14. Cell, 75, 843-854. http://www.ncbi.nlm.nih.gov/pubmed/8252621
Tüfekci, K.U., Oner, M.G., Meuwissen, R.L.J. and Genc, S. (2014) The Role of microRNAs in Human Diseases. Methods in Molecular Biology, 1107, 33-50. http://www.ncbi.nlm.nih.gov/pubmed/24272430
Kim, V.N., Han, J. and Siomi, M.C. (2009) Biogenesis of Small RNAs in Animals. Nature Reviews Molecular Cell Biology, 10, 126-139. http://www.ncbi.nlm.nih.gov/pubmed/19165215
Chapman, E.J. and Carrington, J.C. (2007) Specialization and Evolution of Endogenous Small RNA Pathways. Nature Reviews Genetics, Nature Publishing Group, 8, 884-896.
Allmer, J. (2014) Computational and Bioinformatics Methods for microRNA Gene Prediction. Methods in Molecular Biology, 1107, 157-175. http://www.ncbi.nlm.nih.gov/pubmed/24272436
Hamzeiy, H., Allmer, J. and Yousef, M. (2014) Computational Methods for microRNA Target Prediction. Methods in Molecular Biology, 1107, 207-221. http://www.ncbi.nlm.nih.gov/pubmed/24272439
Sa?ar, M.D. and Allmer, J. (2013) Comparison of Four ab Initio microRNA Prediction Tools. Proceedings of the International Conference on Bioinformatics Models, Methods and Algorithms, SciTePress—Science and and Technology Publications, Barcelona, 190-195. http://www.scitepress.org/DigitalLibrary/Link.aspx?doi=10.5220/0004248201900195
de ON Lopes, I., Schliep, A. and de Carvalho, A.C.P. de L.F. (2014) The Discriminant Power of RNA Features for Pre-miRNA Recognition. BMC Bioinformatics, 15, 124. http://dx.doi.org/10.1186/1471-2105-15-124 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4046174&tool=pmcentrez&rendertype= abstract
Kozomara, A. and Griffiths-Jones, S. (2011) miRBase: Integrating microRNA Annotation and Deep-Sequencing Data. Nucleic Acids Research, 39, D152-D157. http://dx.doi.org/10.1093/nar/gkq1027 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3013655&tool=pmcentrez&rendertype= abstract
Weber, M.J. (2005) New Human and Mouse microRNA Genes Found by Homology Search. FEBS Journal, 272, 59-73. http://www.ncbi.nlm.nih.gov/pubmed/15634332 http://dx.doi.org/10.1111/j.1432-1033.2004.04389.x
Lim, L.P., Lau, N.C., Weinstein, E.G., Abdelhakim, A., Yekta, S., Rhoades, M.W., et al. (2003) The microRNAs of Caenorhabditis elegans. Genes & Development, 17, 991-1008. http://www.ncbi.nlm.nih.gov/pubmed/12672692 http://dx.doi.org/10.1101/gad.1074403
Grad, Y., Aach, J., Hayes, G.D., Reinhart, B.J., Church, G.M., Ruvkun, G., et al. (2003) Computational and Experimental Identification of C. elegans microRNAs. Molecular Cell, 11, 1253-1263. http://www.ncbi.nlm.nih.gov/pubmed/12769849 http://dx.doi.org/10.1016/S1097-2765(03)00153-9
Teune, J.-H. and Steger, G. (2010) NOVOMIR: De Novo Prediction of MicroRNA-Coding Regions in a Single Plant-Genome. Journal of Nucleic Acids, 2010, Article ID: 495904. http://www.ncbi.nlm.nih.gov/pubmed/20871826 http://dx.doi.org/10.4061/2010/495904
Ding, J., Zhou, S. and Guan, J. (2010) MiRenSVM: Towards Better Prediction of microRNA Precursors Using an Ensemble SVM Classifier with Multi-Loop Features. BMC Bioinformatics, 11, S11. http://www.ncbi.nlm.nih.gov/pubmed/21172046 http://dx.doi.org/10.1186/1471-2105-11-s11-s11
Xue, C., Li, F., He, T., Liu, G.-P., Li, Y. and Zhang, X. (2005) Classification of Real and Pseudo microRNA Precursors Using Local Structure-Sequence Features and Support Vector Machine. BMC Bioinformatics, 6, 310. http://www.ncbi.nlm.nih.gov/pubmed/16381612 http://dx.doi.org/10.1186/1471-2105-6-310
Jiang, P., Wu, H., Wang, W., Ma, W., Sun, X. and Lu, Z. (2007) MiPred: Classification of Real and Pseudo microRNA Precursors Using Random Forest Prediction Model with Combined Features. Nucleic Acids Research, 35, W339-W344. http://www.ncbi.nlm.nih.gov/pubmed/17553836 http://dx.doi.org/10.1093/nar/gkm368
Keshavan, R., Virata, M., Keshavan, A. and Zeller, R.W. (2010) Computational Identification of Ciona intestinalis microRNAs. Zoological Science, 27, 162-170. http://www.ncbi.nlm.nih.gov/pubmed/20141421 http://dx.doi.org/10.2108/zsj.27.162
Lagos-Quintana, M., Rauhut, R., Lendeckel, W. and Tuschl, T. (2001) Identification of Novel Genes Coding for Small Expressed RNAs. Science, 294, 853-858. http://www.ncbi.nlm.nih.gov/pubmed/11679670 http://dx.doi.org/10.1126/science.1064921
Lau, N.C., Lim, L.P., Weinstein, E.G. and Bartel, D.P. (2001) An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans. Science, 294, 858-862. http://www.ncbi.nlm.nih.gov/pubmed/11679671 http://dx.doi.org/10.1126/science.1065062
Lee, R.C. and Ambros, V. (2001) An Extensive Class of Small RNAs in Caenorhabditis elegans. Science, 294, 862-864. http://dx.doi.org/10.1126/science.1065329
Pasquinelli, A.E., Reinhart, B.J., Slack, F., Martindale, M.Q., Kuroda, M.I., Maller, B., et al. (2000) Conservation of the Sequence and Temporal Expression of Let-7 Heterochronic Regulatory RNA. Nature, 408, 86-89. http://www.ncbi.nlm.nih.gov/pubmed/11081512 http://dx.doi.org/10.1038/35040556
Wang, X., Zhang, J., Li, F., Gu, J., He, T., Zhang, X., et al. (2005) MicroRNA Identification Based on Sequence and Structure Alignment. Bioinformatics, 21, 3610-3614. http://www.ncbi.nlm.nih.gov/pubmed/15994192 http://dx.doi.org/10.1093/bioinformatics/bti562
Hertel, J. and Stadler, P.F. (2006) Hairpins in a Haystack: Recognizing microRNA Precursors in Comparative Genomics Data. Bioinformatics, 22, 197-202. http://www.ncbi.nlm.nih.gov/pubmed/16873472 http://dx.doi.org/10.1093/bioinformatics/btl257
Ritchie, W., Gao, D. and Rasko, J.E.J. (2012) Defining and Providing Robust Controls for microRNA Prediction. Bioinformatics, 28, 1058-1061. http://www.ncbi.nlm.nih.gov/pubmed/22408193 http://dx.doi.org/10.1093/bioinformatics/bts114
Wu, Y., Wei, B., Liu, H., Li, T. and Rayner, S. (2011) MiRPara: A SVM-Based Software Tool for Prediction of Most Probable microRNA Coding Regions in Genome Scale Sequences. BMC Bioinformatics, 12, 107. http://www.ncbi.nlm.nih.gov/pubmed/21504621 http://dx.doi.org/10.1186/1471-2105-12-107
Yousef, M., Jung, S., Showe, L.C. and Showe, M.K. (2008) Learning from Positive Examples When the Negative Class Is Undetermined—microRNA Gene Identification. Algorithms for Molecular Biology, 3, 2. http://www.ncbi.nlm.nih.gov/pubmed/18226233 http://dx.doi.org/10.1186/1748-7188-3-2
Sewer, A., Paul, N., Landgraf, P., Aravin, A., Pfeffer, S., Brownstein, M.J., et al. (2005) Identification of Clustered microRNAs Using an ab Initio Prediction Method. BMC Bioinformatics, 6, 267. http://www.ncbi.nlm.nih.gov/pubmed/16274478 http://dx.doi.org/10.1186/1471-2105-6-267
Gomes, C.P.C., Cho, J.-H., Hood, L., Franco, O.L., Pereira, R.W. and Wang, K. (2013) A Review of Computational Tools in microRNA Discovery. Frontiers in Genetics, 4, 81. http://dx.doi.org/10.3389/fgene.2013.00081 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3654206&tool=pmcentrez&rendertype= abstract
Billoud, B., Nehr, Z., Le Bail, A. and Charrier, B. (2014) Computational Prediction and Experimental Validation of microRNAs in the Brown Alga Ectocarpus siliculosus. Nucleic Acids Research, 42, 417-429. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3874173&tool=pmcentrez&rendertype= abstract http://dx.doi.org/10.1093/nar/gkt856
Oliveira, J.S., Mendes, N.D., Carocha, V., Graca, C., Paiva, J.A. and Freitas, A.T. (2013) A Computational Approach for MicroRNA Identification in Plants: Combining Genome-Based Predictions with RNA-Seq Data. Journal of Data Mining in Genomics & Proteomics, 4, 130. http://www.omicsonline.org/2153-0602/2153-0602-4-130.php?aid=14889 http://dx.doi.org/10.4172/2153-0602.1000130
Xuan, P., Guo, M., Liu, X., Huang, Y., Li, W. and Huang, Y. (2011) PlantMiRNAPred: Efficient Classification of Real and Pseudo Plant Pre-miRNAs. Bioinformatics, 27, 1368-1376. http://www.ncbi.nlm.nih.gov/pubmed/21441575 http://dx.doi.org/10.1093/bioinformatics/btr153
Williams, P.H., Eyles, R. and Weiller, G. (2012) Plant MicroRNA Prediction by Supervised Machine Learning Using C5.0 Decision Trees. Journal of Nucleic Acids, 2012, Article ID: 652979. http://dx.doi.org/10.1155/2012/652979 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3503367&tool=pmcentrez&rendertype= abstract
Cakir, M.V. and Allmer, J. (2010) Systematic Computational Analysis of Potential RNAi Regulation in Toxoplasma gondii. Proceedings of the 5th International Symposium on Health Informatics and Bioinformatics, Ankara, 20-22 April 2010, 31-38. http://dx.doi.org/10.1109/hibit.2010.5478909
Adai, A., Johnson, C., Mlotshwa, S., Archer-Evans, S., Manocha, V., Vance, V., et al. (2005) Computational Prediction of miRNAs in Arabidopsis thaliana. Genome Research, 15, 78-91. http://dx.doi.org/10.1101/gr.2908205
Rajagopalan, R., Vaucheret, H., Trejo, J. and Bartel, D.P. (2006) A Diverse and Evolutionarily Fluid Set of microRNAs in Arabidopsis thaliana. Genes & Development, 20, 3407-3425. http://dx.doi.org/10.1101/gad.1476406 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1698448&tool=pmcentrez&rendertype= abstract
Jain, M., Chevala, V.V.S.N. and Garg, R. (2014) Genome-Wide Discovery and Differential Regulation of Conserved and Novel microRNAs in Chickpea via Deep Sequencing. Journal of Experimental Botany, 65, 5945-5958. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4203128&tool=pmcentrez&rendertype= abstract http://dx.doi.org/10.1093/jxb/eru333
Berezikov, E., Cuppen, E. and Plasterk, R.H.A. (2006) Approaches to microRNA Discovery. Nature Genetics, 38, 2-7. http://www.ncbi.nlm.nih.gov/pubmed/16736019 http://dx.doi.org/10.1038/ng1794
Dai, X., Zhuang, Z. and Zhao, P.X. (2011) Computational Analysis of miRNA Targets in Plants: Current Status and Challenges. Briefings in Bioinformatics, 12, 115-121. http://www.ncbi.nlm.nih.gov/pubmed/20858738 http://dx.doi.org/10.1093/bib/bbq065
Kurtoglu, K.Y., Kantar, M., Lucas, S.J. and Budak, H. (2013) Unique and Conserved microRNAs in Wheat Chromosome 5D Revealed by Next-Generation Sequencing. PLoS ONE, 8, e69801. http://dx.doi.org/10.1371/journal.pone.0069801 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3720673&tool=pmcentrez&rendertype= abstract
Bailey, T.L., Boden, M., Buske, F.A., Frith, M., Grant, C.E., Clementi, L., et al. (2009) MEME SUITE: Tools for Motif Discovery and Searching. Nucleic Acids Research, 37, W202-W208. http://dx.doi.org/10.1093/nar/gkp335 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2703892&tool=pmcentrez&rendertype= abstract
Bailey, T.L. and Elkan, C. (1994) Fitting a Mixture Model by Expectation Maximization to Discover Motifs in Biopolymers. Proceedings of the International Conference on Intelligent Systems for Molecular Biology, 2, 28-36. http://www.ncbi.nlm.nih.gov/pubmed/7584402
Yan, T., Yoo, D., Berardini, T.Z., Mueller, L.A., Weems, D.C., Weng, S., et al. (2005) PatMatch: A Program for Finding Patterns in Peptide and Nucleotide Sequences. Nucleic Acids Research, 33, W262-W266. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1160129&tool=pmcentrez&rendertype= abstract http://dx.doi.org/10.1093/nar/gki368
van der Burgt, A., Fiers, M.W.J.E., Nap, J.-P. and van Ham, R.C.H.J. (2009) In Silico miRNA Prediction in Metazoan Genomes: Balancing between Sensitivity and Specificity. BMC Genomics, 10, 204. http://www.biomedcentral.com/1471-2164/10/204/ http://dx.doi.org/10.1186/1471-2164-10-204
Bentwich, I. (2008) Identifying Human microRNAs. Current Topics in Microbiology and Immunology, 320, 257-269. http://dx.doi.org/10.1007/978-3-540-75157-1_12
Nam, J.-W., Shin, K.-R., Han, J., Lee, Y., Kim, V.N. and Zhang, B.-T. (2005) Human microRNA Prediction through a Probabilistic Co-Learning Model of Sequence and Structure. Nucleic Acids Research, 33, 3570-3581. http://www.ncbi.nlm.nih.gov/pubmed/15987789 http://dx.doi.org/10.1093/nar/gki668
Nam, J.-W., Kim, J., Kim, S.-K., Zhang, B.-T. (2006) ProMiR II: A Web Server for the Probabilistic Prediction of Clustered, Nonclustered, Conserved and Nonconserved microRNAs. Nucleic Acids Research, 34, W455-W458. http://www.ncbi.nlm.nih.gov/pubmed/16845048 http://dx.doi.org/10.1093/nar/gkl321
Ng, K.L.S. and Mishra, S.K. (2007) De Novo SVM Classification of Precursor microRNAs from Genomic Pseudo Hairpins Using Global and Intrinsic Folding Measures. Bioinformatics, 23, 1321-1330. http://www.ncbi.nlm.nih.gov/pubmed/17267435 http://dx.doi.org/10.1093/bioinformatics/btm026
Thain, D., Tannenbaum, T. and Livny, M. (2005) Distributed Computing in Practice: The Condor Experience. Concurrency and Computation: Practice and Experience, 17, 2-4. http://dx.doi.org/10.1002/cpe.938 http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.6.3035
Guyon, I., Weston, J., Barnhill, S. and Vapnik, V. (2002) Gene Selection for Cancer Classification Using Support Vector Machines. Machine Learning, 46, 389-422. http://link.springer.com/article/10.1023%2FA%3A1012487302797 http://dx.doi.org/10.1023/A:1012487302797
Vapnik, V.N. (1995) The Nature of Statistical Learning Theory. Springer-Verlag, New York. http://dl.acm.org/citation.cfm?id=211359 http://dx.doi.org/10.1007/978-1-4757-2440-0
Gewehr, J.E., Szugat, M. and Zimmer, R. (2007) BioWeka—Extending the Weka Framework for Bioinformatics. Bioinformatics, 23, 651-653. http://www.ncbi.nlm.nih.gov/pubmed/17237069 http://dx.doi.org/10.1093/bioinformatics/btl671
Chang, C.-C. and Lin, C.-J. (2011) LIBSVM. ACM Transactions on Intelligent Systems and Technology, 2, 1-27. http://dl.acm.org/citation.cfm?doid=1961189.1961199 http://dx.doi.org/10.1145/1961189.1961199
Batuwita, R. and Palade, V. (2009) microPred: Effective Classification of Pre-miRNAs for Human miRNA Gene Prediction. Bioinformatics, 25, 989-995. http://www.ncbi.nlm.nih.gov/pubmed/19233894 http://dx.doi.org/10.1093/bioinformatics/btp107
Zhang, B.H., Pan, X.P., Cox, S.B., Cobb, G.P. and Anderson, T.A. (2006) Evidence That miRNAs Are Different from Other RNAs. Cellular and Molecular Life Sciences, 63, 246-254. http://dx.doi.org/10.1007/s00018-005-5467-7
Sacar, M.D. and Allmer, J. (2014) Machine Learning Methods for microRNA Gene Prediction. Methods in Molecular Biology, 1107, 177-187. http://www.ncbi.nlm.nih.gov/pubmed/24272437 http://dx.doi.org/10.1007/978-1-62703-748-8_10
Accurate Plant MicroRNA Prediction Can Be Achieved Using Sequence Motif Features — Oak Academic Publishing