Accurately predicting the secondary structure of RNA, particularly for long non-coding RNA, has direct implications in healthcare, where it can be used for diagnostic, therapeutic, and drug discovery purposes. However, the majority of previous approaches are too costly in terms of computation budget to cope with the increasing complexity of long RNAs, and the ones that can scale to long RNAs lack accuracy to reliably predict their structures. We propose a new approach combining recursive cutting and machine learning techniques for predicting the secondary structures of long non-coding RNAs. In comparison, our method proves to be computationally efficient by recursively partitioning a sequence into smaller fragments until they can be easily managed by an existing model. We perform a benchmark of different state-of-the-art models and show that our approach indeed demonstrates better performance for long RNAs and a potential to bring significant improvements in the future, as well as interesting enhancing properties, which we discuss.

RNAs can interact with other molecules in their environment, such as ions, proteins or other RNAs, to form complexes with important biological roles. The prediction of the structure of these complexes is therefore an important issue and a difficult task. We are interested in RNA complexes composed of several (more than two) interacting RNAs. We show how available knowledge on the considered RNAs can help predict their secondary structure. We propose an interactive tool for the prediction of RNA complexes, called C-RCPRed, that considers user knowledge and probing data (which can be generated experimentally or artificially). C-RCPred is based on a multi-objective optimization algorithm. Through an extensive benchmarking procedure, which includes state-of-the-art methods, we show the efficiency of the multi-objective approach and the positive impact of considering user knowledge and probing data on the prediction results. C-RCPred is freely available as an open-source program and web server on the EvryRNA website (https://evryrna.ibisc.univ-evry.fr).

MOTIVATION: Applied research in machine learning progresses faster when a clean dataset is available and ready to use. Several datasets have been proposed and released over the years for specific tasks such as image classification, speech-recognition and more recently for protein structure prediction. However, for the fundamental problem of RNA structure prediction, information is spread between several databases depending on the level we are interested in: sequence, secondary structure, 3D structure or interactions with other macromolecules. In order to speed-up advances in machine-learning based approaches for RNA secondary and/or 3D structure prediction, a dataset integrating all this information is required, to avoid spending time on data gathering and cleaning. RESULTS: Here, we propose the first attempt of a standardized and automatically generated dataset dedicated to RNA combining together: RNA sequences, homology information (under the form of position-specific scoring matrices) and information derived by annotation of available 3D structures (including secondary structure, canonical and non-canonical interactions and backbone torsion angles). The data are retrieved from public databases PDB, Rfam and SILVA. The paper describes the procedure to build such dataset and the RNA structure descriptors we provide. Some statistical descriptions of the resulting dataset are also provided. AVAILABILITY AND IMPLEMENTATION: The dataset is updated every month and available online (in flat-text file format) on the EvryRNA software platform (https://evryrna.ibisc.univ-evry.fr/evryrna/rnanet). An efficient parallel pipeline to build the dataset is also provided for easy reproduction or modification. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: RNA loops have been modelled and clustered from solved 3D structures into ordered collections of recurrent non-canonical interactions called 'RNA modules', available in databases. This work explores what information from such modules can be used to improve secondary structure prediction. We propose a bi-objective method for predicting RNA secondary structures by minimizing both an energy-based and a knowledge-based potential. The tool, called BiORSEO, outputs secondary structures corresponding to the optimal solutions from the Pareto set. RESULTS: We compare several approaches to predict secondary structures using inserted RNA modules information: two module data sources, Rna3Dmotif and the RNA 3D Motif Atlas, and different ways to score the module insertions: module size, module complexity or module probability according to models like JAR3D and BayesPairing. We benchmark them against a large set of known secondary structures, including some state-of-the-art tools, and comment on the usefulness of the half physics-based, half data-based approach. AVAILABILITY AND IMPLEMENTATION: The software is available for download on the EvryRNA website, as well as the datasets. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: RNAs can interact and form complexes, which have various biological roles. The secondary structure prediction of those complexes is a first step towards the identification of their 3D structure. We propose an original approach that takes advantage of the high number of RNA secondary structure and RNA-RNA interaction prediction tools. We formulate the problem of RNA complex prediction as the determination of the best combination (according to the free energy) of predicted RNA secondary structures and RNA-RNA interactions. RESULTS: We model those predicted structures and interactions as a graph in order to have a combinatorial optimization problem that is a constrained maximum weight clique problem. We propose an heuristic based on Breakout Local Search to solve this problem and a tool, called RCPred, that returns several solutions, including motifs like internal and external pseudoknots. On a large number of complexes, RCPred gives competitive results compared to the methods of the state of the art. CONCLUSIONS: We propose in this paper a method called RCPred for the prediction of several secondary structures of RNA complexes, including internal and external pseudoknots. As further works we will propose an improved computation of the global energy and the insertion of 3D motifs in the RNA complexes.

RNA structure prediction is an important field in bioinformatics, and numerous methods and tools have been proposed. Pseudoknots are specific motifs of RNA secondary structures that are difficult to predict. Almost all existing methods are based on a single model and return one solution, often missing the real structure. An alternative approach would be to combine different models and return a (small) set of solutions, maximizing its quality and diversity in order to increase the probability that it contains the real structure. We propose here an original method for predicting RNA secondary structures with pseudoknots, based on integer programming. We developed a generic bi-objective integer programming algorithm allowing to return optimal and sub-optimal solutions optimizing simultaneously two models. This algorithm was then applied to the combination of two known models of RNA secondary structure prediction, namely MEA and MFE. The resulting tool, called BiokoP, is compared with the other methods in the literature. The results show that the best solution (structure with the highest F1-score) is, in most cases, given by BiokoP. Moreover, the results of BiokoP are homogeneous, regardless of the pseudoknot type or the presence or not of pseudoknots. Indeed, the F1-scores are always higher than 70% for any number of solutions returned. The results obtained by BiokoP show that combining the MEA and the MFE models, as well as returning several optimal and several sub-optimal solutions, allow to improve the prediction of secondary structures. One perspective of our work is to combine better mono-criterion models, in particular to combine a model based on the comparative approach with the MEA and the MFE models. This leads to develop in the future a new multi-objective algorithm to combine more than two models. BiokoP is available on the EvryRNA platform: https://EvryRNA.ibisc.univ-evry.fr .

We are given a set of n jobs and a single processor that can vary its speed dynamically. Each job J_j is characterized by its processing requirement (work) p_j, its release date r_j and its deadline d_j. We are also given a budget of energy E and we study the scheduling problem of maximizing the throughput (i.e. the number of jobs that are completed on time). While the preemptive energy minimization problem has been solved in polynomial time [Yao et al., FOCS'95], the complexity of the problem of maximizing the throughput remained open until now. We answer partially this question by providing a dynamic programming algorithm that solves the problem in pseudo-polynomial time. While our result shows that the problem is not strongly NP-hard, the question of whether the problem can be solved in polynomial time remains a challenging open question. Our algorithm can also be adapted for solving the weighted version of the problem where every job is associated with a weight w_j and the objective is the maximization of the sum of the weights of the jobs that are completed on time.

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