Detection of long non–coding RNA homology, a comparative study on alignment and alignment–free metrics

Abstract

BackgroundLong non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment–based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task.ResultsIn this study we compare alignment–based and alignment–free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment–free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish.ConclusionsThe obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs.Electronic supplementary materialThe online version of this article (10.1186/s12859-018-2441-6) contains supplementary material, which is available to authorized users.

The molecular structure of long non-coding RNAs: emerging patterns and functional implications

“…The general paradigm that similar sequences determine similar structures, and similar structures are in turn responsible for similar biological functions is barely applicable to lncRNAs, because evolutionary pressure does not only act on lncRNA sequence, but also on their structure, function, and genomic synteny (Diederichs 2014). As a result, the molecular properties of homologous lncRNAs often differ significantly (Chillon and Pyle 2016;Kirk et al 2018;Noviello et al 2018). But these considerations should not surprise, because the sequence-structure-function paradigm has numerous exceptions in proteins, too (Martin et al 1998).…”

RNAsamba: neural network-based assessment of the protein-coding potential of RNA sequences

“…As only a fraction of the genetic diversity existing in nature is known and available in databases, many new protein-coding genes are not identified because their protein product is not found among existing data ( 6 ). On the other side, as lncRNAs are not under the same evolutionary constraints as mRNAs, they display lower sequence conservation than protein-coding transcripts ( 7 , 8 ), resulting in failure to find homologous sequences in database searches ( 9 , 10 ).…”

Association of HIVEP3 Gene and Lnc RNA with Femoral Neck Bone Mineral Content and Hip Geometry by Genome-Wide Association Analysis in Chinese People

“…Because LncRNA lacked reading frames, they almost never participated in protein-coding. More evidence showed that LncRNA transcribed by DNA was not useless; they participated in a variety of biological processes and regulated gene expression at the RNA level [ 26 , 27 ]. About 15779 LncRNAs had been recorded in the human genome ( https://www.gencodegenes.org/ ) [ 28 ].…”