Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine

Abstract

Background: MicroRNAs (miRNAs) are a group of short (approximately 22 nt) non-coding RNAs that play important regulatory roles. MiRNA precursors (pre-miRNAs) are characterized by their hairpin structures. However, a large amount of similar hairpins can be folded in many genomes. Almost all current methods for computational prediction of miRNAs use comparative genomic approaches to identify putative pre-miRNAs from candidate hairpins. Ab initio method for distinguishing pre-miRNAs from sequence segments with pre-miRNA-like hairpin structures is lacking. Being able to classify real vs. pseudo pre-miRNAs is important both for understanding of the nature of miRNAs and for developing ab initio prediction methods that can discovery new miRNAs without known homology.

Results: A set of novel features of local contiguous structure-sequence information is proposed for distinguishing the hairpins of real pre-miRNAs and pseudo pre-miRNAs. Support vector machine (SVM) is applied on these features to classify real vs. pseudo pre-miRNAs, achieving about 90% accuracy on human data. Remarkably, the SVM classifier built on human data can correctly identify up to 90% of the pre-miRNAs from other species, including plants and virus, without utilizing any comparative genomics information.

Conclusion: The local structure-sequence features reflect discriminative and conserved characteristics of miRNAs, and the successful ab initio classification of real and pseudo pre-miRNAs opens a new approach for discovering new miRNAs.

Figure 1

Using the triplet elements to represent the local structure-sequence features of the hairpin. The triplet element is composed of the 3 continuous sub-structures and the nucleotide type at the middle. The appearances of all 32 possible triplet elements are counted along a hairpin segment, forming a 32-dimensional vector, which is then normalized to be the input vector for SVM.

Figure 2

The average appearance frequencies of the triplet elements in the two classes (real pre-miRNA vs. pseudo-miRNA hairpins).