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Abstract In this paper, NeuralProphet (NP), an explainable hybrid modular framework, enhances the forecasting performance of pandemics by adding two neural network modules; auto-regressor (AR) and lagged-regressor (LR). An advanced deep auto-regressor neural network (Deep-AR-Net) model is employed to implement these two modules. The enhanced NP is optimized via AdamW and Huber loss function to perform multivariate multi-step forecasting contrast to Prophet. The models are validated with COVID-19 time-series datasets. The NP’s efficiency is studied component-wise for a long-term forecast for India and an overall reduction of 60.36% and individually 34.7% by AR-module, 53.4% by LR-module in MASE compared to Prophet. The Deep-AR-Net model reduces the forecasting error of NP for all five countries, on average, by 49.21% and 46.07% for short-and-long-term, respectively. The visualizations confirm that forecasting curves are closer to the actual cases but significantly different from Prophet. Hence, it can develop a real-time decision-making system for highly infectious diseases. 

The global rise in heart disease necessitates precise prediction tools to assess individual risk levels. This paper introduces a novel Multi-Objective Artificial Bee Colony Optimized Hybrid Deep Belief Network and XGBoost (HDBN-XG) algorithm, enhancing coronary heart disease prediction accuracy. Key physiological data, including Electrocardiogram (ECG) readings and blood volume measurements, are analyzed. The HDBN-XG algorithm assesses data quality, normalizes using z-score values, extracts features via the Computational Rough Set method, and constructs feature subsets using the Multi-Objective Artificial Bee Colony approach. Our findings indicate that the HDBN-XG algorithm achieves an accuracy of 99%, precision of 95%, specificity of 98%, sensitivity of 97%, and F1-measure of 96%, outperforming existing classifiers. This paper contributes to predictive analytics by offering a data-driven approach to healthcare, providing insights to mitigate the global impact of coronary heart disease. 

The ongoing COVID-19 pandemic continues to infect people worldwide, and the virus continues to evolve in significant ways which can pose challenges to the efficiency of available vaccines and therapeutic drugs and cause future pandemic. Therefore, it is important to investigate the binding and interaction of ACE2 with different RBD variants. A comparative study using all-atom MD simulations was conducted on ACE2 binding with 8 different RBD variants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N and N501YE484K- K417N on RBD. Based on the RMSD, RMSF, and DSSP results, overall the binding of RBD variants with ACE2 is stable, and the secondary structure of RBD and ACE2 are consistent after the point mutation. Besides that, a similar buried surface area, a consistent binding interface and a similar amount of hydrogen bonds formed between RBD and ACE2 although the exact residue pairs on the binding interface were modified. The change of binding free energy from point mutation was predicted using the free energy perturbation (FEP) method. It is found that N501Y, N439K, and K417N can strengthen the binding of RBD with ACE2, while E484K and P479S weaken the binding, and S477N and T478I have negligible effect on the binding. Point mutations modified the dynamic correlation of residues in RBD based on the dihedral angle covariance matrix calculation. Doing dynamic network analysis, a common intrinsic network community extending from the tail of RBD to central, then to the binding interface region was found, which could communicate the dynamics in the binding interface region to the tail thus to the other sections of S protein. The result can supply unique methodology and molecular insight on studying the molecular structure and dynamics of possible future pandemics and design novel drugs. 

The SARS-CoV-2 main protease (M^pro) is a major therapeutic target. The M^proinhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As M^proinhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as an approximation for M^proactivity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays identified substitutions which conferred strong nirmatrelvir resistance and others that compromised activity. On the other hand, N142A and the P132H mutation, carried by the Omicron variant, caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of M^proE166R, and M^proE166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of M^prothat may arise as M^proantivirals become more widely used.