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Aptamers can be regarded as efficient substitutes for monoclonal antibodies in many diagnostic and therapeutic applications. Due to the tedious and prohibitive nature of SELEX (systematic evolution of ligands by exponential enrichment), the in silico methods have been developed to improve the enrichment processes rate. However, the majority of these methods did not show any effort in designing novel aptamers. Moreover, some target proteins may have not any binding RNA candidates in nature and a reductive mechanism is needed to generate novel aptamer pools among enormous possible combinations of nucleotide acids to be examined in vitro. We have applied a genetic algorithm (GA) with an embedded binding predictor fitness function to in silico design of RNA aptamers. As a case study of this research, all steps were accomplished to generate an aptamer pool against aminopeptidase N (CD13) biomarker. First, the model was developed based on sequential and structural features of known RNA-protein complexes. Then, utilizing RNA sequences involved in complexes with positive prediction results, as the first-generation, novel aptamers were designed and top-ranked sequences were selected. A 76-mer aptamer was identified with the highest fitness value with a 3 to 6 time higher score than parent oligonucleotides. The reliability of obtained sequences was confirmed utilizing docking and molecular dynamic simulation. The proposed method provides an important simplified contribution to the oligonucleotide-aptamer design process. Also, it can be an underlying ground to design novel aptamers against a wide range of biomarkers., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

The performance of a model in machine learning problems highly depends on the dataset and training algorithms. Choosing the right training algorithm can change the tale of a model. While some algorithms have a great performance in some datasets, they may fall into trouble in other datasets. Moreover, by adjusting hyperparameters of an algorithm, which controls the training processes, the performance can be improved. This study contributes a method to tune hyperparameters of machine learning algorithms using Grey Wolf Optimization (GWO) and Genetic algorithm (GA) metaheuristics. Also, 11 different algorithms including Averaged Perceptron, FastTree, FastForest, Light Gradient Boost Machine (LGBM), Limited memory Broyden Fletcher Goldfarb Shanno algorithm Maximum Entropy (LbfgsMxEnt), Linear Support Vector Machine (LinearSVM), and a Deep Neural Network (DNN) including four architectures are employed on 11 datasets in different biological, biomedical, and nature categories such as molecular interactions, cancer, clinical diagnosis, behavior related predictions, RGB images of human skin, and X-rays images of Covid19 and cardiomegaly patients. Our results show that in all trials, the performance of the training phases is improved. Also, GWO demonstrates a better performance with a p-value of 2.6E-5. Moreover, in most experiment cases of this study, the metaheuristic methods demonstrate better performance and faster convergence than Exhaustive Grid Search (EGS). The proposed method just receives a dataset as an input and suggests the best-explored algorithm with related arguments. So, it is appropriate for datasets with unknown distribution, machine learning algorithms with complex behavior, or users who are not experts in analytical statistics and data science algorithms. [Display omitted] • The proposed method can improve the performance of the machine learning model independent from the composition of datasets. • It assists to gain a better performance faster than tuning by blindly and randomly chosen hyperparameters. • The idea of this method is general and it is not specific to a limited number of training algorithms and optimizers. • This method is convenient to use for users who are not experts in algorithm designing, also for real-world problems. • Generally, metaheuristic methods give better result and converge faster than blind approaches like Exhaustive Grid Search. [ABSTRACT FROM AUTHOR]

Feature extraction is one of the most important preprocessing steps in predicting the interactions between RNAs and proteins by applying machine learning approaches. Despite many efforts in this area, still, no suitable structural feature extraction tool has been designed. Therefore, an online toolbox, named RPINBASE which can be applied to different scopes of biological applications, is introduced in this paper. This toolbox employs efficient nested queries that enhance the speed of the requests and produces desired features in the form of positive and negative samples. To show the capabilities of the proposed toolbox, the developed toolbox was investigated in the aptamer design problem, and the obtained results are discussed. RPINBASE is an online toolbox and is accessible at http://rpinbase.com. • Generating queryable positive samples from PDB complexes • Generating queryable artificial proposed negative samples (based on family and clan) • Providing a wide range of extracted features for primary and secondary structures of RNA and protein macromolecules. • Selecting efficient and high performance dataset powered by preprocessed and stored data to download feature vectors quickly. • Possibility of sample filtering by PDB information and structural features of macromolecules. [ABSTRACT FROM AUTHOR]