Background: Psoriasis is an autoimmune inflammatory skin disease that affects 0.5–3% of the world’s population and current treatment options are posed with limitations. The reduced risk of failure in clinical trials for repositioned drug candidates and the time and cost-effectiveness has popularized drug reposition and computational methods in the drug research community. Results: The current study attempts to reposition approved drugs for the treatment of psoriasis by docking about 2000 approved drug molecules against fifteen selected and validated anti-psoriatic targets. The docking results showed that a good number of the dataset interacted favorably with the targets as most of them had − 11.00 to − 10.00 kcal/mol binding free energies across the targets. The percentage of the dataset with binding affinity higher than the co-crystallized ligands ranged from 34.76% (JAK-3) to 0.73% (Rac-1). It was observed that 12 out of the 0.73% outperformed all the co-crystallized ligands across the 15 studied proteins. All the 12 drugs identified are currently indicated as either antiviral or anticancer drugs and are of purine and pyrimidine nuclei. This is not surprising given that there is similarity in the mechanism of the mentioned diseases. Conclusion: This study, therefore, suggests that; antiviral and anticancer drugs could have anti-psoriatic effects, and molecules with purine and pyrimidine structural architecture are likely templates to consider in developing anti-psoriatic agents.

Background: In most parts of the world, especially in underdeveloped countries, acquired immunodeficiency syndrome (AIDS) still remains a major cause of death, disability, and unfavorable economic outcomes. This has necessitated intensive research to develop effective therapeutic agents for the treatment of human immunodeficiency virus (HIV) infection, which is responsible for AIDS. Peptide cleavage by HIV-1 protease is an essential step in the replication of HIV-1. Thus, correct and timely prediction of the cleavage site of HIV-1 protease can significantly speed up and optimize the drug discovery process of novel HIV-1 protease inhibitors. In this work, we built and compared the performance of selected machine learning models for the prediction of HIV-1 protease cleavage site utilizing a hybrid of octapeptide sequence information comprising bond composition, amino acid binary profile (AABP), and physicochemical properties as numerical descriptors serving as input variables for some selected machine learning algorithms. Our work differs from antecedent studies exploring the same subject in the combination of octapeptide descriptors and method used. Instead of using various subsets of the dataset for training and testing the models, we combined the dataset, applied a 3-way data split, and then used a "stratified" 10-fold cross-validation technique alongside the testing set to evaluate the models. Results: Among the 8 models evaluated in the “stratified” 10-fold CV experiment, logistic regression, multi-layer perceptron classifier, linear discriminant analysis, gradient boosting classifier, Naive Bayes classifier, and decision tree classifier with AUC, F-score, and B. Acc. scores in the ranges of 0.91–0.96, 0.81–0.88, and 80.1–86.4%, respectively, have the closest predictive performance to the state-of-the-art model (AUC 0.96, F-score 0.80 and B. Acc. ~ 80.0%). Whereas, the perceptron classifier and the K-nearest neighbors had statistically lower performance (AUC 0.77–0.82, F-score 0.53–0.69, and B. Acc. 60.0–68.5%) at p < 0.05. On the other hand, logistic regression, and multi-layer perceptron classifier (AUC of 0.97, F-score > 0.89, and B. Acc. > 90.0%) had the best performance on further evaluation on the testing set, though linear discriminant analysis, gradient boosting classifier, and Naive Bayes classifier equally performed well (AUC > 0.94, F-score > 0.87, and B. Acc. > 86.0%). Conclusions: Logistic regression and multi-layer perceptron classifiers have comparable predictive performances to the state-of-the-art model when octapeptide sequence descriptors consisting of AABP, bond composition and standard physicochemical properties are used as input variables. In our future work, we hope to develop a standalone software for HIV-1 protease cleavage site prediction utilizing the linear regression algorithm and the aforementioned octapeptide sequence descriptors.

Differentiated thyroid cancer (DTC) is a common endocrine malignancy with rising incidence and frequent recurrence, despite a generally favorable prognosis. Accurate recurrence prediction is critical for guiding post-treatment strategies. This study aimed to enhance predictive performance by refining feature engineering and evaluating a diverse ensemble of machine learning models using the UCI DTC dataset. Unsupervised data engineering—specifically dimensionality reduction and clustering—was used to improve feature quality. Principal Component Analysis (PCA) and Truncated Singular Value Decomposition (t-SVD) were selected based on superior clustering metrics: adjusted Rand Index (ARI > 0.55) and V-measure (> 0.45). These were integrated into classification pipelines using Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbors (KNN), Feedforward Neural Network (FNN), and Gradient Boosting (GB). Model performance was evaluated through bootstrapping on an independent test set, stratified 10-fold cross-validation (CV), and subgroup analyses. Metrics included balanced accuracy, F1 score, AUC, sensitivity, specificity, and precision, each reported with 95% confidence intervals (CIs). SHAP analysis supported model interpretability. The PCA-based LR pipeline achieved the best test set performance: balanced accuracy of 0.95 (95% CI: 0.90–0.99), AUC of 0.99 (95% CI: 0.97–1.00), and sensitivity of 0.94 (95% CI: 0.84–1.00). In stratified CV, it maintained strong results (balanced accuracy: 0.86; AUC: 0.97; sensitivity: 0.80), with consistent performance across clinically relevant subgroups. The t-SVD-based LR pipeline showed comparable performance on both test and CV sets. SVM and FNN pipelines also performed robustly (test AUCs > 0.99; CV AUCs > 0.96). RF and KNN had high specificity but slightly lower sensitivity (test: ~0.87; CV: 0.77–0.80). GB pipelines showed the lowest overall performance (test balanced accuracy: 0.86–0.88; CV: 0.85–0.88). Dimensionality reduction via PCA and t-SVD significantly improved model performance, particularly for LR, SVM, FNN, RF and KNN classifiers. The PCA-based LR pipeline showed the best generalizability, supporting its potential integration into clinical decision-support tools for personalized DTC management. Not applicable.

Background/Objectives: Thyroid cancer, particularly well-differentiated thyroid cancer, is one of the most prevalent endocrine malignancies, with a rising incidence. Although it generally has a favorable prognosis, recurrence is common. Accurate prediction of recurrence is crucial for optimizing treatment plans and improving patient outcomes. This study aimed to advance the state-of-the-art in thyroid cancer recurrence prediction by refining feature engineering techniques and exploring a diverse ensemble of machine learning algorithms and an artificial neural network, using the differentiated thyroid cancer dataset from the UCI Machine Learning Repository; Methods: Various unsupervised data engineering methods, such as dimensionality reduction and clustering, were employed to enhance feature quality and mitigate noise, using stratified 10-fold cross-validation. The best-performing dimensionality reduction techniques were used to build classification model pipelines employing each of several machine learning models and an artificial neural network. The performance of these classification pipelines were assessed using metrics sensitive to class imbalance; Results: Principal Component Analysis and Truncated Singular Value Decomposition achieved superior clustering performance and moderate variances in their first principal components. Logistic Regression, Random Forest, Support Vector Machine, K-Nearest Neighbors, and Feedforward Neural Network models all achieved high performance, with Logistic Regression pipelines demonstrating balanced accuracy, F1 score, AUC, sensitivity, specificity, and precision—all greater than 0.93 on the test set and slightly lower in 10-fold cross-validation. Gradient Boosting classification pipelines performed the lowest, though still with respectable metrics; Conclusions: This study shows that employing feature engineering techniques like Principal Component Analysis or Truncated Singular Value Decomposition in Logistic Regression, Random Forest, Feedforward Neural Networks, Support Vector Machine, and K-Nearest Neighbors classification pipelines can improve thyroid cancer recurrence prediction accuracy and reliability, supporting more personalized treatment strategies in post-treatment patients.

Hexokinases (Hks) and mitochondrial complex I (MCI) are involved in the energy metabolism of cells; glycolysis/fermentation and oxidative phosphorylation. Both Hks and MCI are known to play critical roles in either division of metabolic plasticity which enables tumor progression and proliferation in the presence of chemotherapies. Therefore, targeting these enzymes are important in cancer drug resistance. Here, computational models for the prediction of inhibition of Hks were developed based on experimental data and an optimal feature subset that was selected by the Boruta algorithm (a wrapper feature selection algorithm coupled with random forest). Out of the seven models that were explored, a random forest classifier gave the best prediction (GA = 0.84, FNR = 0.12 and AUC = 0.96 for the external dataset). Fragmentation analysis led to the identification of the unique structural scaffolds that characterize hexokinase inhibitors and non-inhibitors. The best Hks inhibition model predicted that 23 molecules out of the 191 dataset of MCI actives (IC₅₀ ≤ 10 µM) that were screened, have more than 60 % probability of exhibiting Hk inhibitory activity. Hence, they are possible dual inhibitors of both targets. Furthermore, the 23 molecules’ core structures are members of the scaffolds that are unique to Hk inhibitors earlier predicted by fragment analysis. The need for dual targeting agents in cancer therapy, particularly in combating cancer drug resistance, highlights the relevance of these findings.