smORFunction: A Tool for Predicting Functions of Small Open Reading Frames and Microproteins

Abstract

Background Small open reading frame (smORF) is open reading frame with a length of less than 100 codons. Microproteins, translated from smORFs, have been found to participate in a variety of biological processes such as muscle formation and contraction, cell proliferation, and immune activation. Although previous studies have collected and annotated a large abundance of smORFs, functions of the vast majority of smORFs are still unknown. It is thus increasingly important to develop computational methods to annotate the functions of these smORFs. Results In this study, we collected 617,462 unique smORFs from three studies. The expression of smORF RNAs was estimated by reannotated microarray probes. Using a speed-optimized correlation algorism, the functions of smORFs were predicted by their correlated genes with known functional annotations. After applying our method to 5 known microproteins from literatures, our method successfully predicted their functions. Further validation from the UniProt database showed that at least one function of 202 out of 270 microproteins was predicted. Conclusions We developed a method, smORFunction, to provide function predictions of smORFs/microproteins in at most 265 models generated from 173 datasets, including 48 tissues/cells, 82 diseases (and normal). The tool can be available at http://www.cuilab.cn/smorfunction.

No one tool to rule them all: prokaryotic gene prediction tool annotations are highly dependent on the organism of study

“…The unallocated space (24 074–24 170) resulted in Prodigal reporting the next downstream CDS starting at 24 091 instead of 24 133 (as in the Ensembl annotation), erroneously including 5' UTR in the predicted CDS. There are now tools to identify putative short ORFs in both prokaryotes and eukaryotes using additional evidence, such as RNA expression data ( Bartholomäus et al , 2021 ; Ji et al , 2020 ; Miravet-Verde et al , 2019 ). Our results suggest that the identification of short and overlapping CDSs cannot be done independently without the potential for unforeseen consequences for annotation accuracy.…”