PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3′ UTRs and coding sequences

The purpose of the proposed web server, publicly available at http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies primarily mRNA transcripts targeted in their 3′ untranslated regions (3′ UTRs), and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding sequences (CDSs). While PACCMIT belongs among the accurate algorithms for predicting conserved microRNA targets in the 3′ UTRs, the main contribution of the web server is 2-fold: PACCMIT provides an accurate tool for predicting targets also of weakly conserved or non-conserved microRNAs, whereas PACCMIT-CDS addresses the lack of similar portals adapted specifically for targets in CDS. The web server asks the user for microRNAs and mRNAs to be analyzed, accesses the precomputed P-values for all microRNA–mRNA pairs from a database for all mRNAs and microRNAs in a given species, ranks the predicted microRNA–mRNA pairs, evaluates their significance according to the false discovery rate and finally displays the predictions in a tabular form. The results are also available for download in several standard formats.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[3]  Scott B. Dewell,et al.  Transcriptome-wide Identification of RNA-Binding Protein and MicroRNA Target Sites by PAR-CLIP , 2010, Cell.

[4]  Terrence S. Furey,et al.  The UCSC Table Browser data retrieval tool , 2004, Nucleic Acids Res..

[5]  Jirí Vanícek,et al.  Efficient use of accessibility in microRNA target prediction , 2010, Nucleic Acids Res..

[6]  Arnold J. Levine,et al.  A Relative-Entropy Algorithm for Genomic Fingerprinting Captures Host-Phage Similarities , 2005, Journal of bacteriology.

[7]  Jirí Vanícek,et al.  Searching the coding region for microRNA targets. , 2013, RNA.

[8]  D. Bartel MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[9]  J. Kitzman,et al.  Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. , 2007, RNA.

[10]  J. Vaníček,et al.  Host MicroRNA Regulation of Human Cytomegalovirus Immediate Early Protein Translation Promotes Viral Latency , 2014, Journal of Virology.

[11]  James M. Reecy,et al.  Prediction of Altered 3′- UTR miRNA-Binding Sites from RNA-Seq Data: The Swine Leukocyte Antigen Complex (SLA) as a Model Region , 2012, PloS one.

[12]  Jirí Vanícek,et al.  Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: Implications for latency , 2008, Proceedings of the National Academy of Sciences.

[13]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[14]  Ray M. Marín,et al.  Optimal Use of Conservation and Accessibility Filters in MicroRNA Target Prediction , 2012, PloS one.

[15]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[16]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[17]  Ray M. Marín,et al.  Analysis of the accessibility of CLIP bound sites reveals that nucleation of the miRNA:mRNA pairing occurs preferentially at the 3'-end of the seed match. , 2012, RNA.

[18]  Ana Kozomara,et al.  miRBase: integrating microRNA annotation and deep-sequencing data , 2010, Nucleic Acids Res..

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

[20]  M. Kiebler,et al.  Faculty Opinions recommendation of Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. , 2009 .

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

[22]  William H Press,et al.  Human microRNAs target a functionally distinct population of genes with AT-rich 3′ UTRs , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[24]  A. Fuglsang,et al.  The relationship between palindrome avoidance and intragenic codon usage variations: a Monte Carlo study. , 2004, Biochemical and biophysical research communications.

[25]  Y. Li,et al.  Incorporating structure to predict microRNA targets. , 2005, Proceedings of the National Academy of Sciences of the United States of America.