DEBFold: Computational Identification of RNA Secondary Structures for Sequences across Structural Families Using Deep Learning.

It is now known that RNAs play more active roles in cellular pathways beyond simply serving as transcription templates. These biological mechanisms might be mediated by higher RNA stereo conformations, triggering the need to understand RNA secondary structures first. However, experimental protocols for solving RNA structures are unavailable for large-scale investigation due to their high costs and time-consuming nature. Various computational tools were thus developed to predict the RNA secondary structures from sequences. Recently, deep networks have been investigated to help predict RNA structures directly from their sequences. However, existing deep-learning-based tools are more or less suffering from model overfitting due to their complicated problem formulation and defective model training processes, limiting their applications across sequences from different structural families. In this research, we designed a two-stage RNA structure prediction strategy called DEBFold (deep ensemble boosting and folding) based on convolution encoding/decoding and self-attention mechanisms to enhance the existing thermodynamic structure models. Moreover, the model training process followed rigorous steps to achieve an acceptable prediction generalization. On the family-wise reserved test sets and the PDB-derived test set, DEBFold achieves better structure prediction performance over traditional tools and existing deep-learning methods. In summary, we obtained a cutting-edge deep-learning-based structure prediction tool with supreme across-family generalization performance. The DEBFold tool can be accessed at https://cobis.bme.ncku.edu.tw/DEBFold/.