Abstract Protein S-sulfenylation is one kind of crucial post-translational modifications (PTMs) in which the hydroxyl group covalently binds to the thiol of cysteine. Some recent studies have shown that this modification plays an important role in signaling transduction, transcriptional regulation and apoptosis. To date, the dynamic of sulfenic acids in proteins remains unclear because of its fleeting nature. Identifying S-sulfenylation sites, therefore, could be the key to decipher its mysterious structures and functions, which are important in cell biology and diseases. However, due to the lack of effective methods, scientists in this field tend to be limited in merely a handful of some wet lab techniques that are time-consuming and not cost-effective. Thus, this motivated us to develop an in silico model for detecting S-sulfenylation sites only from protein sequence information. In this study, protein sequences served as natural language sentences comprising biological subwords. The deep neural network was consequentially employed to perform classification. The performance statistics within the independent dataset including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the curve rates achieved 85.71%, 69.47%, 77.09%, 0.5554 and 0.833, respectively. Our results suggested that the proposed method (fastSulf-DNN) achieved excellent performance in predicting S-sulfenylation sites compared to other well-known tools on a benchmark dataset.

Antioxidant proteins are involved importantly in many aspects of cellular life activities. They protect the cell and DNA from oxidative substances (such as peroxide, nitric oxide, oxygen-free radicals, etc.) which are known as reactive oxygen species (ROS). Free radical generation and antioxidant defenses are opposing factors in the human body and the balance between them is necessary to maintain a healthy body. An unhealthy routine or the degeneration of age can break the balance, leading to more ROS than antioxidants, causing damage to health. In general, the antioxidant mechanism is the combination of antioxidant molecules and ROS in a one-electron reaction. Creating computational models to promptly identify antioxidant candidates is essential in supporting antioxidant detection experiments in the laboratory. In this study, we proposed a machine learning-based model for this prediction purpose from a benchmark set of sequencing data. The experiments were conducted by using 10-fold cross-validation on the training process and validated by three different independent datasets. Different machine learning and deep learning algorithms have been evaluated on an optimal set of sequence features. Among them, Random Forest has been identified as the best model to identify antioxidant proteins with the highest performance. Our optimal model achieved high accuracy of 84.6%, as well as a balance in sensitivity (81.5%) and specificity (85.1%) for antioxidant protein identification on the training dataset. The performance results from different independent datasets also showed the significance in our model compared to previously published works on antioxidant protein identification.

The skeleton is one of the most important organs in the human body in assisting our motion and activities; however, bone density attenuates gradually as we age. Among common bone diseases are osteoporosis and Paget's, two of the most frequently found diseases in the elderly. Nowadays, a combination of multiple drugs is the optimal therapy to decelerate osteoporosis and Paget's pathologic process, which comes with various underlying adverse effects due to drug‐drug interactions (DDIs). Artificial intelligence (AI) has the potential to evaluate the interaction, pharmacodynamics, and possible side effects between drugs. In this research, we created an AI‐based machine‐learning model to predict the outcomes of interactions between drugs used for osteoporosis and Paget's treatment, which helps mitigate the cost and time to implement the best combination of medications in clinical practice. In this study, a DDI dataset was collected from the DrugBank database within the osteoporosis and Paget diseases. We then extracted a variety of chemical features from the simplified molecular‐input line‐entry system (SMILES) of defined drug pairs that interact with each other. Finally, machine‐learning algorithms were implemented to learn the extracted features. Our stack ensemble model from Random Forest and XGBoost reached an average accuracy of 74 % in predicting DDIs. It was superior to individual models as well as previous methods in terms of most measurement metrics. This study showed the potential of AI models in predicting DDIs of Osteoporosis‐Paget's disease in particular, and other diseases in general.

This study aimed to create a risk score generated from CT-based radiomics signatures that could be used to predict overall survival in patients with non-small cell lung cancer (NSCLC). We retrospectively enrolled three sets of NSCLC patients (including 336, 84, and 157 patients for training, testing, and validation set, respectively). A total of 851 radiomics features for each patient from CT images were extracted for further analyses. The most important features (strongly linked with overall survival) were chosen by pairwise correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and univariate Cox proportional hazard regression. Multivariate Cox proportional hazard model survival analysis was used to create risk scores for each patient, and Kaplan–Meier was used to separate patients into two groups: high-risk and low-risk, respectively. ROC curve assessed the prediction ability of the risk score model for overall survival compared to clinical parameters. The risk score, which developed from ten radiomics signatures model, was found to be independent of age, gender, and stage for predicting overall survival in NSCLC patients (HR, 2.99; 95% CI, 2.27–3.93; p < 0.001) and overall survival prediction ability was 0.696 (95% CI, 0.635–0.758), 0.705 (95% CI, 0.649–0.762), 0.657 (95% CI, 0.589–0.726) (AUC) for 1, 3, and 5 years, respectively, in the training set. The risk score is more likely to have a better accuracy in predicting survival at 1, 3, and 5 years than clinical parameters, such as age 0.57 (95% CI, 0.499–0.64), 0.552 (95% CI, 0.489–0.616), 0.621 (95% CI, 0.544–0.689) (AUC); gender 0.554, 0.546, 0.566 (AUC); stage 0.527, 0.501, 0.459 (AUC), respectively, in 1, 3 and 5 years in the training set. In the training set, the Kaplan–Meier curve revealed that NSCLC patients in the high-risk group had a lower overall survival time than the low-risk group (p < 0.001). We also had similar results that were statistically significant in the testing and validation set. In conclusion, risk scores developed from ten radiomics signatures models have great potential to predict overall survival in NSCLC patients compared to the clinical parameters. This model was able to stratify NSCLC patients into high-risk and low-risk groups regarding the overall survival prediction.