Journal Article

Functional classification of long non-coding RNAs by k-mer content

Wang, Shuo, Weeks, Kevin M., Baker, Allison R., Sprague, Daniel, Collins, David W., Kim, Susan O., Kirk, Jessime M., Lee, David M., Schertzer, Megan D., Inoue, Kaoru, Mucha, Peter J., Wooten, Joshua S., Chen, Qidi, Smola, Matthew J., Calabrese, J. Mauro, Horning, Christopher R.

2018

Overview

The functions of most long non-coding RNAs (lncRNAs) are unknown. In contrast to proteins, lncRNAs with similar functions often lack linear sequence homology; thus, the identification of function in one lncRNA rarely informs the identification of function in others. We developed a sequence comparison method to deconstruct linear sequence relationships in lncRNAs and evaluate similarity based on the abundance of short motifs called k-mers. We found that lncRNAs of related function often had similar k-mer profiles despite lacking linear homology, and that k-mer profiles correlated with protein binding to lncRNAs and with their subcellular localization. Using a novel assay to quantify Xist-like regulatory potential, we directly demonstrated that evolutionarily unrelated lncRNAs can encode similar function through different spatial arrangements of related sequence motifs. K-mer-based classification is a powerful approach to detect recurrent relationships between sequence and function in lncRNAs. SEEKR is a method that deconstructs linear sequence relationships between lncRNAs and evaluates similarity on the basis of abundance of short motifs called k-mers. LncRNAs of related function often have similar k-mer profiles despite lacking linear homology.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 13/109 / 45/44 / 45/70 / 631/114/2184 / 631/208/200 / 631/208/212/2019 / 631/337/176 / 64/60 / Agriculture / Algorithms / Animal Genetics and Genomics / Animals / Base Sequence / Binding sites / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosomes / Classification / Cluster Analysis / Coding / Conserved Sequence / Databases, Genetic / Functional analysis (Mathematics) / Gene expression / Gene Function / Genomes / Hep G2 Cells / Homology / Human Genetics / Humans / Hypotheses / K562 Cells / Localization / Mice / Molecular Sequence Annotation / Nucleic Acid Conformation / Nucleotide Motifs - genetics / Potassium Channels, Voltage-Gated - genetics / Protein binding / Proteins / RNA / RNA, Long Noncoding - chemistry / RNA, Long Noncoding - classification / RNA, Long Noncoding - genetics / Sequence Alignment / Sequence Analysis, RNA - methods