SQUARNA - an RNA secondary structure prediction method based on a greedy stem formation model

ABSTRACT Non-coding RNAs play a diverse range of roles in various cellular processes, with their spatial structure being pivotal to their function. The RNA’s secondary structure is a key determinant of its overall fold. Given the scarcity of experimentally determined RNA 3D structures, understanding the secondary structure is vital for discerning the molecule’s function. Currently, there is no universally effective solution for de novo RNA secondary structure prediction. Existing methods are becoming increasingly complex without marked improvements in accuracy, and they often overlook critical elements such as pseudoknots. In this work, we introduce SQUARNA, a novel approach to de novo RNA secondary structure prediction. This method utilizes a simple, greedy stem formation model, addressing many of the limitations inherent in previous tools. Our benchmarks demonstrate that SQUARNA matches the performance of leading methods for single sequence inputs and significantly surpasses existing tools when applied to sequence alignment inputs.