Literature-based condition-specific miRNA-mRNA target prediction

PLoS One. 2017 Mar 31;12(3):e0174999. doi: 10.1371/journal.pone.0174999. eCollection 2017.

Abstract

miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3'-UTR of genes. Many recent studies have reported that miRNAs play important biological roles by regulating specific mRNAs or genes. Many sequence-based target prediction algorithms have been developed to predict miRNA targets. However, these methods are not designed for condition-specific target predictions and produce many false positives; thus, expression-based target prediction algorithms have been developed for condition-specific target predictions. A typical strategy to utilize expression data is to leverage the negative control roles of miRNAs on genes. To control false positives, a stringent cutoff value is typically set, but in this case, these methods tend to reject many true target relationships, i.e., false negatives. To overcome these limitations, additional information should be utilized. The literature is probably the best resource that we can utilize. Recent literature mining systems compile millions of articles with experiments designed for specific biological questions, and the systems provide a function to search for specific information. To utilize the literature information, we used a literature mining system, BEST, that automatically extracts information from the literature in PubMed and that allows the user to perform searches of the literature with any English words. By integrating omics data analysis methods and BEST, we developed Context-MMIA, a miRNA-mRNA target prediction method that combines expression data analysis results and the literature information extracted based on the user-specified context. In the pathway enrichment analysis using genes included in the top 200 miRNA-targets, Context-MMIA outperformed the four existing target prediction methods that we tested. In another test on whether prediction methods can re-produce experimentally validated target relationships, Context-MMIA outperformed the four existing target prediction methods. In summary, Context-MMIA allows the user to specify a context of the experimental data to predict miRNA targets, and we believe that Context-MMIA is very useful for predicting condition-specific miRNA targets.

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / physiology
  • Algorithms
  • Computational Biology
  • Humans
  • Literature*
  • MicroRNAs / metabolism*
  • PubMed
  • RNA, Messenger / metabolism*
  • Software

Substances

  • 3' Untranslated Regions
  • MicroRNAs
  • RNA, Messenger

Grants and funding

This work was supported by grant numbers 2012M3A9D1054622, 2014M3C9A3063541, and 2012M3C4A7033341, National Research Foundation of Korea (URL: http://www.nrf.re.kr/nrf_tot_cms/index.jsp?pmi-sso-return2=none). The authors who received the funding are: Minsik, Sungmin, Ji Hwan, Heejoon, Sunwon, Jaewoo, Sun. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.