Christos Koroulis

The observation and analysis of RNA molecules have proved crucial for the understanding of various processes in nature. Scientists have mined knowledge and drawn conclusions using experimental methods for decades. Leveraging advanced computational methods in recent years has led to fast and more accurate results in all areas of interest. One highly challenging task, in terms of RNA analysis, is the prediction of its structure, which provides valuable information about how it transforms and operates numerous significant tasks in organisms. In this paper, we focus on the prediction of the 2-D or secondary structure of RNA, specifically, on a rare but yet complex type of pseudoknot, the L-type pseudoknot, extending our previous framework specialized for H-type pseudoknots. We propose a grammar-based framework that predicts all possible L-type pseudoknots of a sequence in a reasonable response time, leveraging also the advantages of core biological principles, such as maximum base pairs and minimum free energy. In order to evaluate the effectiveness of our methodology, we assessed four performance metrics: precision; recall; Matthews correlation coefficient (MCC); and F1-score, which is the harmonic mean of precision and recall. Our methodology outperformed the other three well known methods in terms of Precision, with a score of 0.844, while other methodologies scored 0.500, 0.333, and 0.308. Regarding the F1-score, our platform scored 0.671, while other methodologies scored 0.661, 0.449, and 0.449. The proposed methodology surpassed all methods in terms of the MCC metric, achieving a score of 0.521. The proposed method was added to our RNA toolset, which aims to enhance the capabilities of biologists in the prediction of RNA motifs, including pseudoknots, and holds the potential to be applied in a multitude of biological domains, including gene therapy, drug design, and comprehending RNA functionality. Furthermore, the suggested approach can be employed in conjunction with other methodologies to enhance the precision of RNA structure prediction.