ASSA: Fast identification of statistically significant interactions between long RNAs.

Ivan Antonov,Yulia Medvedeva,Maria Zamkova,Andrey Marakhonov

doi:10.1142/s0219720018400012

Abstract

The discovery of thousands of long noncoding RNAs (lncRNAs) in mammals raises a question about their functionality. It has been shown that some of them are involved in post-transcriptional regulation of other RNAs and form inter-molecular duplexes with their targets. Sequence alignment tools have been used for transcriptome-wide prediction of RNA-RNA interactions. However, such approaches have poor prediction accuracy since they ignore RNA's secondary structure. Application of the thermodynamics-based algorithms to long transcripts is not computationally feasible on a large scale. Here, we describe a new computational pipeline ASSA that combines sequence alignment and thermodynamics-based tools for efficient prediction of RNA-RNA interactions between long transcripts. To measure the hybridization strength, the sum energy of all the putative duplexes is computed. The main novelty implemented in ASSA is the ability to quickly estimate the statistical significance of the observed interaction energies. Most of the functional hybridizations between long RNAs were classified as statistically significant. ASSA outperformed 11 other tools in terms of the Area Under the Curve on two out of four test sets. Additionally, our results emphasized a unique property of the [Formula: see text] repeats with respect to the RNA-RNA interactions in the human transcriptome. ASSA is available at https://sourceforge.net/projects/assa/.

Highlights

Due to the single strand nature of an RNA molecule its nucleotides are capable of base pairing with the complementary nucleotides
We evaluate the ASSA performance on a set of experimentally validated functional natural antisense transcripts (NATs)
Our analysis indicates that ASSA can potentially be used to search for the Long noncoding RNAs (lncRNAs) functioning via short-trans antisense duplexes

Summary

Introduction

Due to the single strand nature of an RNA molecule its nucleotides are capable of base pairing with the complementary nucleotides. A part of one RNA molecule can bind to a complementary part of another RNA molecule forming inter-molecular duplex. Such RNA-RNA pairing is called antisense interaction and the corresponding RNAs are known as natural antisense transcripts or NATs [1]. Due to the functional diversity [5] the role and/or the molecular mechanism of only a few hundred lncRNAs have been determined to date. It has been shown that some of them function post-transcriptionally via formation of inter-molecular RNA-RNA duplexes [6, 7, 8]

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