MMG4: Recognition of G4-Forming Sequences Based on Markov Model

G-quadruplexes (G4s) are special nucleic acid structures with various important biological functions. Existing tools and technologies for G4-forming sequences recognition are limited to time-consuming and costly methods such as circular dichroism and nuclear magnetic resonance. Developing a fast and accurate model for G4-forming sequences recognition has far-reaching significance. In this study, MMG4, a novel model to recognize G4-forming sequences based on Markov model (MM), was developed and the phenomenon of high recognition accuracy in the central region of the sequence and low accuracy in the two end regions was discovered. It was further found that the differences in base transfer probabilities, ratio distribution, and G4-motif structural content in different regions may be the causes of this phenomenon. The study also explored the impact of sequence length on recognition accuracy and found the optimal recognition interval to be [910-1049], with the highest recognition accuracy reaching 85.95%. By extracting sequence features, the study constructed three types of machine learning models: random forest (RF), support vector machine, and back-propagation neural network. It was found that recognition performance of MM was significantly better than that of the other three machine learning models, proving that the recognition method based on MM can effectively capture the correlation information between adjacent nucleotides of G4. By combining MM with the three machine learning models, the predictive performance of MMG4 improved. Among them, the RF model combined with MM has the best performance, achieving an area under the receiver operating characteristic curve value of 0.93 and an area under the precision-recall curve value of 0.9. Finally, the study validated the model robustness and generalization ability through independent testing dataset.