MultiMiTar: A Novel Multi Objective Optimization based miRNA-Target Prediction Method

Background Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. Methodology/Principal Finding In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. Conclusions/Significance MultiMiTar is found to achieve much higher Matthew’s correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from −0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

[1]  Tongbin Li,et al.  miRecords: an integrated resource for microRNA–target interactions , 2008, Nucleic Acids Res..

[2]  Sanghamitra Bandyopadhyay,et al.  TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples , 2009, Bioinform..

[3]  Doron Betel,et al.  The microRNA.org resource: targets and expression , 2007, Nucleic Acids Res..

[4]  Ujjwal Maulik,et al.  A Simulated Annealing-Based Multiobjective Optimization Algorithm: AMOSA , 2008, IEEE Transactions on Evolutionary Computation.

[5]  R. K. Ursem Multi-objective Optimization using Evolutionary Algorithms , 2009 .

[6]  Chi-Ying F. Huang,et al.  miRTarBase: a database curates experimentally validated microRNA–target interactions , 2010, Nucleic Acids Res..

[7]  Vladimir Vapnik,et al.  Statistical learning theory , 1998 .

[8]  Vladimir N. Vapnik,et al.  The Nature of Statistical Learning Theory , 2000, Statistics for Engineering and Information Science.

[9]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[10]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.

[11]  Martin Reczko,et al.  The database of experimentally supported targets: a functional update of TarBase , 2008, Nucleic Acids Res..

[12]  Kengo Kinoshita,et al.  Prediction of disordered regions in proteins based on the meta approach , 2008, Bioinform..

[13]  Vladimir Naumovich Vapni The Nature of Statistical Learning Theory , 1995 .

[14]  Dmitrij Frishman,et al.  TargetSpy: a supervised machine learning approach for microRNA target prediction , 2010, BMC Bioinformatics.

[15]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[16]  Martin Reczko,et al.  Lost in translation: an assessment and perspective for computational microRNA target identification , 2009, Bioinform..

[17]  C. Burge,et al.  Most mammalian mRNAs are conserved targets of microRNAs. , 2008, Genome research.

[18]  Xiaowei Wang,et al.  Systematic identification of microRNA functions by combining target prediction and expression profiling , 2006, Nucleic acids research.

[19]  Nectarios Koziris,et al.  DIANA-microT web server: elucidating microRNA functions through target prediction , 2009, Nucleic Acids Res..

[20]  Xianghuo He,et al.  Multiple microRNAs modulate p21Cip1/Waf1 expression by directly targeting its 3′ untranslated region , 2010, Oncogene.

[21]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[22]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[23]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[24]  Louise C. Showe,et al.  Naïve Bayes for microRNA target predictions - machine learning for microRNA targets , 2007, Bioinform..

[25]  Vesselin Baev,et al.  MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence , 2005, Nucleic Acids Res..

[26]  M. Peter,et al.  Targeting of mRNAs by multiple miRNAs: the next step , 2010, Oncogene.