Discovering Misannotated lncRNAs using Deep Learning Training Dynamics

Motivation

Recent experimental evidence has shown that some long noncoding RNAs (lncRNAs) contain small open reading frames (sORFs) that are translated into functional micropeptides, suggesting that these lncRNAs are misannotated as noncoding. Current methods to detect misannotated lncRNAs rely on ribosome-profiling (Ribo-Seq) and mass-spectrometry experiments, which are cell-type dependent and expensive.

Results

Here, we propose a computational method to identify possible misannotated lncRNAs from sequence information alone. Our approach first builds deep learning models to discriminate coding and non-coding transcripts and leverages these models’ training dynamics to identify misannotated lncRNAs—i.e. lncRNAs with coding potential. The set of misannotated lncRNAs we identified significantly overlap with experimentally validated ones and closely resemble coding protein sequences as evidenced by significant BLAST hits. Our analysis on a subset of misannotated lncRNA candidates also shows that some ORFs they contain yield high confidence folded structures as predicted by AlphaFold2. This methodology offers promising potential for assisting experimental efforts in characterizing the hidden proteome encoded by misannotated lncRNAs and for curating better datasets for building coding potential predictors.

Availability

Source code is available at this link.