Prediction of conserved precursors of miRNAs and their mature forms by integrating position-specific structural features

PLoS One. 2012;7(9):e44314. doi: 10.1371/journal.pone.0044314. Epub 2012 Sep 5.

Abstract

MicroRNA (miRNA) precursor hairpins have a unique secondary structure, nucleotide length, and nucleotide content that are in most cases evolutionarily conserved. The aim of this study was to utilize position-specific features of miRNA hairpins to improve their identification. To this end, we defined the evolutionary and structurally conserved features in each position of miRNA hairpins with heuristically derived values, which were successfully integrated using a probabilistic framework. Our method, miRRim2, can not only accurately detect miRNA hairpins, but infer the location of a mature miRNA sequence. To evaluate the accuracy of miRRim2, we designed a cross validation test in which the whole human genome was used for evaluation. miRRim2 could more accurately detect miRNA hairpins than the other computational predictions that had been performed on the human genome, and detect the position of the 5'-end of mature miRNAs with sensitivity and positive predictive value (PPV) above 0.4. To further evaluate miRRim2 on independent data, we applied it to the Ciona intestinalis genome. Our method detected 47 known miRNA hairpins among top 115 candidates, and pinpointed the 5'-end of mature miRNAs with sensitivity and PPV about 0.4. When our results were compared with deep-sequencing reads of small RNA libraries from Ciona intestinalis cells, we found several candidates in which the predicted mature miRNAs were in good accordance with deep-sequencing results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Ciona intestinalis / genetics*
  • Computational Biology / methods*
  • Conserved Sequence
  • Evolution, Molecular
  • Genetic Vectors
  • Genome
  • Genome, Human
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Nucleic Acid Conformation
  • Predictive Value of Tests
  • RNA Precursors / metabolism
  • Reproducibility of Results
  • Sequence Analysis, DNA

Substances

  • MicroRNAs
  • RNA Precursors

Grants and funding

This work was supported partly by a Grant-in-Aid for Scientific Research (A) and the Functional RNA Project of the New Energy and Industrial Technology Development Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.