In biological systems, Glutamic acid is a crucial amino acid which is used in protein biosynthesis. Carboxylation of glutamic acid is a significant post-translational modification which plays important role in blood coagulation by activating prothrombin to thrombin. Contrariwise, 4-carboxy-glutamate is also found to be involved in diseases including plaque atherosclerosis, osteoporosis, mineralized heart valves, bone resorption and serves as biomarker for onset of these diseases. Owing to the pathophysiological significance of 4-carboxyglutamate, its identification is important to better understand pathophysiological systems. The wet lab identification of prospective 4-carboxyglutamate sites is costly, laborious and time consuming due to inherent difficulties of in-vivo, ex-vivo and in vitro experiments. To supplement these experiments, we proposed, implemented, and evaluated a different approach to develop 4-carboxyglutamate site predictors using pseudo amino acid compositions (PseAAC) and deep neural networks (DNNs). Our approach does not require any feature extraction and employs deep neural networks to learn feature representation of peptide sequences and performing classification thereof. Proposed approach is validated using standard performance evaluation metrics. Among different deep neural networks, convolutional neural network-based predictor achieved best scores on independent dataset with accuracy of 94.7%, AuC score of 0.91 and F1-score of 0.874 which shows the promise of proposed approach. The iCarboxE-Deep server is deployed at https://share.streamlit.io/sheraz-n/carboxyglutamate/app.py .
Messenger RNA (mRNA) has emerged as a critical global technology that requires global joint efforts from different entities to develop a COVID-19 vaccine. However, the chemical properties of RNA pose a challenge in utilizing mRNA as a vaccine candidate. For instance, the molecules are prone to degradation, which has a negative impact on the distribution of mRNA among patients. In addition, little is known of the degradation properties of individual RNA bases in a molecule. Therefore, this study aims to investigate whether a hybrid deep learning can predict RNA degradation from RNA sequences. Two deep hybrid neural network models were proposed, namely GCN_GRU and GCN_CNN. The first model is based on graph convolutional neural networks (GCNs) and gated recurrent unit (GRU). The second model is based on GCN and convolutional neural networks (CNNs). Both models were computed over the structural graph of the mRNA molecule. The experimental results showed that GCN_GRU hybrid model outperform GCN_CNN model by a large margin during the test time. Validation of proposed hybrid models is performed by well-known evaluation measures. Among different deep neural networks, GCN_GRU based model achieved best scores on both public and private MCRMSE test scores with 0.22614 and 0.34152, respectively. Finally, GCN_GRU pre-trained model has achieved the highest AuC score of 0.938. Such proven outperformance of GCNs indicates that modeling RNA molecules using graphs is critical in understanding molecule degradation mechanisms, which helps in minimizing the aforementioned issues. To show the importance of the proposed GCN_GRU hybrid model, in silico experiments has been contacted. The in-silico results showed that our model pays local attention when predicting a given position's reactivity and exhibits interesting behavior on neighboring bases in the sequence.