Porpoise: a new approach for accurate prediction of RNA pseudouridine sites.
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ABSTRACT:
SUBMITTER: Li F
PROVIDER: S-EPMC8575008 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As the most abundant RNA modification, pseudouridine plays important roles in many biological processes. Occurring at the uridine site and catalyzed by pseudouridine synthase, the modification has been observed in nearly all kinds of RNA, including transfer RNA, messenger RNA, small nuclear or nucleolar RNA, and ribosomal RNA. Accordingly, its importance to basic research and drug development is self-evident. Despite some experimental technologies have been developed to detect the pseudouridine sites, they are both time-consuming and expensive. Facing the explosive growth of RNA sequences in the postgenomic age, we are challenged to address the problem by computational approaches: For an uncharacterized RNA sequence, can we predict which of its uridine sites can be modified as pseudouridine and which ones cannot? Here a predictor called "iRNA-PseU" was proposed by incorporating the chemical properties of nucleotides and their occurrence frequency density distributions into the general form of pseudo nucleotide composition (PseKNC). It has been demonstrated via the rigorous jackknife test, independent dataset test, and practical genome-wide analysis that the proposed predictor remarkably outperforms its counterpart. For the convenience of most experimental scientists, the web-server for iRNA-PseU was established at http://lin.uestc.edu.cn/server/iRNA-PseU, by which users can easily get their desired results without the need to go through the mathematical details.
| S-EPMC5330936 | biostudies-literature
Project description:Background: Pseudouridine (Ψ) is one of the most abundant RNA modifications found in a variety of RNA types, and it plays a significant role in many biological processes. The key to studying the various biochemical functions and mechanisms of Ψ is to identify the Ψ sites. However, identifying Ψ sites using experimental methods is time-consuming and expensive. Therefore, it is necessary to develop computational methods that can accurately predict Ψ sites based on RNA sequence information. Methods: In this study, we proposed a new model called PseU-ST to identify Ψ sites in Homo sapiens (H. sapiens), Saccharomyces cerevisiae (S. cerevisiae), and Mus musculus (M. musculus). We selected the best six encoding schemes and four machine learning algorithms based on a comprehensive test of almost all of the RNA sequence encoding schemes available in the iLearnPlus software package, and selected the optimal features for each encoding scheme using chi-square and incremental feature selection algorithms. Then, we selected the optimal feature combination and the best base-classifier combination for each species through an extensive performance comparison and employed a stacking strategy to build the predictive model. Results: The results demonstrated that PseU-ST achieved better prediction performance compared with other existing models. The PseU-ST accuracy scores were 93.64%, 87.74%, and 89.64% on H_990, S_628, and M_944, respectively, representing increments of 13.94%, 6.05%, and 0.26%, respectively, higher than the best existing methods on the same benchmark training datasets. Conclusion: The data indicate that PseU-ST is a very competitive prediction model for identifying RNA Ψ sites in H. sapiens, M. musculus, and S. cerevisiae. In addition, we found that the Position-specific trinucleotide propensity based on single strand (PSTNPss) and Position-specific of three nucleotides (PS3) features play an important role in Ψ site identification. The source code for PseU-ST and the data are obtainable in our GitHub repository (https://github.com/jluzhangxinrubio/PseU-ST).
| S-EPMC9892456 | biostudies-literature
Project description:Pseudouridine(Ψ) is widely popular among various RNA modifications which have been confirmed to occur in rRNA, mRNA, tRNA, and nuclear/nucleolar RNA. Hence, identifying them has vital significance in academic research, drug development and gene therapies. Several laboratory techniques for Ψ identification have been introduced over the years. Although these techniques produce satisfactory results, they are costly, time-consuming and requires skilled experience. As the lengths of RNA sequences are getting longer day by day, an efficient method for identifying pseudouridine sites using computational approaches is very important. In this paper, we proposed a multi-channel convolution neural network using binary encoding. We employed k-fold cross-validation and grid search to tune the hyperparameters. We evaluated its performance in the independent datasets and found promising results. The results proved that our method can be used to identify pseudouridine sites for associated purposes. We have also implemented an easily accessible web server at http://103.99.176.239/ipseumulticnn/.
| S-EPMC7901771 | biostudies-literature
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 (Ψ) 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 Ψ 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 Ψ 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 Ψ 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 Ψ sites.
| S-EPMC6114832 | biostudies-literature
Project description:One of the ubiquitous chemical modifications in RNA, pseudouridine modification is crucial for various cellular biological and physiological processes. To gain more insight into the functional mechanisms involved, it is of fundamental importance to precisely identify pseudouridine sites in RNA. Several useful machine learning approaches have become available recently, with the increasing progress of next-generation sequencing technology; however, existing methods cannot predict sites with high accuracy. Thus, a more accurate predictor is required. In this study, a random forest-based predictor named RF-PseU is proposed for prediction of pseudouridylation sites. To optimize feature representation and obtain a better model, the light gradient boosting machine algorithm and incremental feature selection strategy were used to select the optimum feature space vector for training the random forest model RF-PseU. Compared with previous state-of-the-art predictors, the results on the same benchmark data sets of three species demonstrate that RF-PseU performs better overall. The integrated average leave-one-out cross-validation and independent testing accuracy scores were 71.4% and 74.7%, respectively, representing increments of 3.63% and 4.77% versus the best existing predictor. Moreover, the final RF-PseU model for prediction was built on leave-one-out cross-validation and provides a reliable and robust tool for identifying pseudouridine sites. A web server with a user-friendly interface is accessible at http://148.70.81.170:10228/rfpseu.
| S-EPMC7054385 | biostudies-literature
Project description:Pseudouridine is the most prevalent RNA modification and has been found in both eukaryotes and prokaryotes. Currently, pseudouridine has been demonstrated in several kinds of RNAs, such as small nuclear RNA, rRNA, tRNA, mRNA, and small nucleolar RNA. Therefore, its significance to academic research and drug development is understandable. Through biochemical experiments, the pseudouridine site identification has produced good outcomes, but these lab exploratory methods and biochemical processes are expensive and time consuming. Therefore, it is important to introduce efficient methods for identification of pseudouridine sites. In this study, an intelligent method for pseudouridine sites using the deep-learning approach was developed. The proposed prediction model is called iPseU-CNN (identifying pseudouridine by convolutional neural networks). The existing methods used handcrafted features and machine-learning approaches to identify pseudouridine sites. However, the proposed predictor extracts the features of the pseudouridine sites automatically using a convolution neural network model. The iPseU-CNN model yields better outcomes than the current state-of-the-art models in all evaluation parameters. It is thus highly projected that the iPseU-CNN predictor will become a helpful tool for academic research on pseudouridine site prediction of RNA, as well as in drug discovery.
| S-EPMC6488737 | biostudies-literature
Project description:Pseudouridine synthase binds to uridine sites and catalyzes the conversion of uridine to pseudouridine (Ψ). This binding takes place in a specific context and in the conformation of nucleotides. Most machine-learning methods for Ψ site classification use nucleotide frequency as a feature, which may not fully depict the relevant conformation around a Ψ site. Using the power of deep learning and raw sequence, as well as secondary structure features, our tool MU-PseUDeep is designed to capture both the sequence and secondary structure context, which inputs the raw RNA sequence and the predicted secondary structure to two sets of convolutional neural networks. It has shown considerable improvement in Ψ site prediction over existing tools, XG-PseU, PseUI, and iRNA-PseU for both balanced and imbalanced datasets. To the best of our knowledge, this is the most accurate tool for Ψ site prediction. We also used MU-PseUDeep to scan the human transcriptome, which shows that the genes with predicted Ψ sites are enriched in nucleotide and protein binding, as well as in neurodegeneration pathways. The tool is open source, available at https://github.com/smk5g5/MU-PseUDeep.
| S-EPMC7387732 | biostudies-literature
Project description:Two articles recently published in Nature and Cell report the first transcriptome-wide maps of pseudouridine (Ψ) at single-base resolution through selective chemical labeling, suggesting new mechanisms and functions of Ψ in mRNA and non-coding RNA molecules.
| S-EPMC4650566 | biostudies-other
Project description:Pseudouridine is one of the most abundant RNA modifications, occurring when uridines are catalyzed by Pseudouridine synthase proteins. It plays an important role in many biological processes and has been reported to have application in drug development. Recently, the single-molecule sequencing techniques such as the direct RNA sequencing platform offered by Oxford Nanopore technologies have enabled direct detection of RNA modifications on the molecule being sequenced. In this study, we introduce a tool called Penguin that integrates several machine learning (ML) models to identify RNA Pseudouridine sites on Nanopore direct RNA sequencing reads. Pseudouridine sites were identified on single molecule sequencing data collected from direct RNA sequencing resulting in 723 K reads in Hek293 and 500 K reads in Hela cell lines. Penguin extracts a set of features from the raw signal measured by the Oxford Nanopore and the corresponding basecalled k-mer. Those features are used to train the predictors included in Penguin, which in turn, can predict whether the signal is modified by the presence of Pseudouridine sites in the testing phase. We have included various predictors in Penguin, including Support vector machines (SVM), Random Forest (RF), and Neural network (NN). The results on the two benchmark data sets for Hek293 and Hela cell lines show outstanding performance of Penguin either in random split testing or in independent validation testing. In random split testing, Penguin has been able to identify Pseudouridine sites with a high accuracy of 93.38% by applying SVM to Hek293 benchmark dataset. In independent validation testing, Penguin achieves an accuracy of 92.61% by training SVM with Hek293 benchmark dataset and testing it for identifying Pseudouridine sites on Hela benchmark dataset. Thus, Penguin outperforms the existing Pseudouridine predictors in the literature by 16 % higher accuracy than those predictors using independent validation testing. Employing penguin to predict Pseudouridine sites revealed a significant enrichment of "regulation of mRNA 3'-end processing" in Hek293 cell line and 'positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus' in Hela cell line. Penguin software and models are available on GitHub at https://github.com/Janga-Lab/Penguin and can be readily employed for predicting Ψ sites from Nanopore direct RNA-sequencing datasets.
| S-EPMC9232934 | biostudies-literature
Project description:Allostery refers to the biological process by which an effector modulator binds to a protein at a site distant from the active site, known as allosteric site. Identifying allosteric sites is essential for discovering allosteric process and is considered a critical factor in allosteric drug development. To facilitate related research, we developed PASSer (Protein Allosteric Sites Server) at https://passer.smu.edu, a web application for fast and accurate allosteric site prediction and visualization. The website hosts three trained and published machine learning models: (i) an ensemble learning model with extreme gradient boosting and graph convolutional neural network, (ii) an automated machine learning model with AutoGluon and (iii) a learning-to-rank model with LambdaMART. PASSer accepts protein entries directly from the Protein Data Bank (PDB) or user-uploaded PDB files, and can conduct predictions within seconds. The results are presented in an interactive window that displays protein and pockets' structures, as well as a table that summarizes predictions of the top three pockets with the highest probabilities/scores. To date, PASSer has been visited over 49 000 times in over 70 countries and has executed over 6 200 jobs.
| S-EPMC10320119 | biostudies-literature