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Porpoise: a new approach for accurate prediction of RNA pseudouridine sites.

ABSTRACT: Pseudouridine is a ubiquitous RNA modification type present in eukaryotes and prokaryotes, which plays a vital role in various biological processes. Almost all kinds of RNAs are subject to this modification. However, it remains a great challenge to identify pseudouridine sites via experimental approaches, requiring expensive and time-consuming experimental research. Therefore, computational approaches that can be used to perform accurate in silico identification of pseudouridine sites from the large amount of RNA sequence data are highly desirable and can aid in the functional elucidation of this critical modification. Here, we propose a new computational approach, termed Porpoise, to accurately identify pseudouridine sites from RNA sequence data. Porpoise builds upon a comprehensive evaluation of 18 frequently used feature encoding schemes based on the selection of four types of features, including binary features, pseudo k-tuple composition, nucleotide chemical property and position-specific trinucleotide propensity based on single-strand (PSTNPss). The selected features are fed into the stacked ensemble learning framework to enable the construction of an effective stacked model. Both cross-validation tests on the benchmark dataset and independent tests show that Porpoise achieves superior predictive performance than several state-of-the-art approaches. The application of model interpretation tools demonstrates the importance of PSTNPs for the performance of the trained models. This new method is anticipated to facilitate community-wide efforts to identify putative pseudouridine sites and formulate novel testable biological hypothesis.

SUBMITTER: Li F

PROVIDER: S-EPMC8575008 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPseudouridylation is the most prevalent type of posttranscriptional modification in various stable RNAs of all organisms, which significantly affects many cellular processes that are regulated by RNA. Thus, accurate identification of pseudouridine (?) sites in RNA will be of great benefit for understanding these cellular processes. Due to the low efficiency and high cost of current available experimental methods, it is highly desirable to develop computational methods for accurately and efficiently detecting ? sites in RNA sequences. However, the predictive accuracy of existing computational methods is not satisfactory and still needs improvement.ResultsIn this study, we developed a new model, PseUI, for ? sites identification in three species, which are H. sapiens, S. cerevisiae, and M. musculus. Firstly, five different kinds of features including nucleotide composition (NC), dinucleotide composition (DC), pseudo dinucleotide composition (pseDNC), position-specific nucleotide propensity (PSNP), and position-specific dinucleotide propensity (PSDP) were generated based on RNA segments. Then, a sequential forward feature selection strategy was used to gain an effective feature subset with a compact representation but discriminative prediction power. Based on the selected feature subsets, we built our model by using a support vector machine (SVM). Finally, the generalization of our model was validated by both the jackknife test and independent validation tests on the benchmark datasets. The experimental results showed that our model is more accurate and stable than the previously published models. We have also provided a user-friendly web server for our model at http://zhulab.ahu.edu.cn/PseUI , and a brief instruction for the web server is provided in this paper. By using this instruction, the academic users can conveniently get their desired results without complicated calculations.ConclusionIn this study, we proposed a new predictor, PseUI, to detect ? sites in RNA sequences. It is shown that our model outperformed the existing state-of-art models. It is expected that our model, PseUI, will become a useful tool for accurate identification of RNA ? sites.

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Porpoise: a new approach for accurate prediction of RNA pseudouridine sites.

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