miRNA target recognition using features of suboptimal alignments

MicroRNAs (miRNAs) are a class of short RNA molecules that regulate gene expression by binding directly to messenger RNAs. Conventional approaches to miRNA target prediction estimate the accessibility of target sites and the strength of the binding miRNA by finding optimums of some energy models, which involves O(n3) computations. Alternatively, we narrow down potential binding sites of miRNAs to suboptimal hits of a pairwise alignment algorithm called Fitting Alignment in O(n2). We invoke a same algorithm, once for all candidate sites to measure the site accessibilities. These features are applied to a binary classifier being learned to predict true associations between miRNAs and target genes. Training the classifier requires the negative samples indicating non-affected genes. The experiments verifying such negative associations have been rarely performed, so we exploit tissue-specific gene expression data to impute the negative associations. The recall rate of our method is above 70% (at precision 85%).

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

[2]  Stijn van Dongen,et al.  miRBase: tools for microRNA genomics , 2007, Nucleic Acids Res..

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

[4]  B. Li,et al.  Expression profiling reveals off-target gene regulation by RNAi , 2003, Nature Biotechnology.

[5]  Yadong Wang,et al.  Predicting human microRNA-disease associations based on support vector machine , 2013, Int. J. Data Min. Bioinform..

[6]  Takaya Saito,et al.  MicroRNAs--targeting and target prediction. , 2010, New biotechnology.

[7]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..

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

[9]  Louise C. Showe,et al.  Learning from positive examples when the negative class is undetermined- microRNA gene identification , 2008, Algorithms for Molecular Biology.

[10]  Nectarios Koziris,et al.  Accurate microRNA target prediction correlates with protein repression levels , 2009, BMC Bioinformatics.

[11]  Jiang Qian,et al.  TiGER: A database for tissue-specific gene expression and regulation , 2008, BMC Bioinformatics.

[12]  Ivo Grosse,et al.  Functional microRNA targets in protein coding sequences , 2012, Bioinform..

[13]  Dianwei Han,et al.  MicroRNAfold: pre-microRNA secondary structure prediction based on modified NCM model with thermodynamics-based scoring strategy , 2012, Int. J. Data Min. Bioinform..

[14]  Yu-Ping Wang,et al.  MiRTif: a support vector machine-based microRNA target interaction filter , 2008, BMC Bioinformatics.

[15]  L. Lim,et al.  Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. , 2006, RNA.

[16]  Anastasia Khvorova,et al.  3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets , 2006, Nature Methods.

[17]  Ola Snøve,et al.  Weighted sequence motifs as an improved seeding step in microRNA target prediction algorithms. , 2005, RNA.

[18]  Jorma Tarhio,et al.  Identifying human miRNA targets with a genetic algorithm , 2010 .

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

[20]  Dang D. Long,et al.  Potent effect of target structure on microRNA function , 2007, Nature Structural &Molecular Biology.

[21]  Paul Ahlquist,et al.  Statistical Use of Argonaute Expression and RISC Assembly in microRNA Target Identification , 2009, PLoS Comput. Biol..

[22]  Xing Chen,et al.  RWRMDA: predicting novel human microRNA-disease associations. , 2012, Molecular bioSystems.