Drug repurposing aims to find new therapeutic applications for existing drugs in the pharmaceutical market, leading to significant savings in time and cost. The use of artificial intelligence and knowledge graphs to propose repurposing candidates facilitates the process, as large amounts of data can be processed. However, it is important to pay attention to the explainability needed to validate the predictions. We propose a general architecture to understand several explainable methods for graph completion based on knowledge graphs and design our own architecture for drug repurposing. We present XG4Repo (eXplainable Graphs for Repurposing), a framework that takes advantage of the connectivity of any biomedical knowledge graph to link compounds to the diseases they can treat. Our method allows methapaths of different types and lengths, which are automatically generated and optimised based on data. XG4Repo focuses on providing meaningful explanations to the predictions, which are based on paths from compounds to diseases. These paths include nodes such as genes, pathways, side effects, or anatomies, so they provide information about the targets and other characteristics of the biomedical mechanism that link compounds and diseases. Paths make predictions interpretable for experts who can validate them and use them in further research on drug repurposing. We also describe three use cases where we analyse new uses for Epirubicin, Paclitaxel, and Predinisone and present the paths that support the predictions.

The ever-increasing use of generative models in various fields where tabular data is used highlights the need for robust and standardized validation metrics to assess the similarity between real and synthetic data. Current methods lack a unified framework and rely on diverse and often inconclusive statistical measures. Divergences, which quantify discrepancies between data distributions, offer a promising avenue for validation. However, traditional approaches calculate divergences independently for each feature due to the complexity of joint distribution modeling. This paper addresses this challenge by proposing a novel approach that uses divergence estimation to overcome the limitations of marginal comparisons. Our core contribution lies in applying a divergence estimator to build a validation metric considering the joint distribution of real and synthetic data. We leverage a probabilistic classifier to approximate the density ratio between datasets, allowing the capture of complex relationships. We specifically calculate two divergences: the well-known Kullback-Leibler (KL) divergence and the Jensen-Shannon (JS) divergence. KL divergence offers an established use in the field, while JS divergence is symmetric and bounded, providing a reliable metric. The efficacy of this approach is demonstrated through a series of experiments with varying distribution complexities. The initial phase involves comparing estimated divergences with analytical solutions for simple distributions, setting a benchmark for accuracy. Finally, we validate our method on a real-world dataset and its corresponding synthetic counterpart, showcasing its effectiveness in practical applications. This research offers a significant contribution with applicability beyond tabular data and the potential to improve synthetic data validation in various fields.

PURPOSE: Rare cancers constitute over 20% of human neoplasms, often affecting patients with unmet medical needs. The development of effective classification and prognostication systems is crucial to improve the decision-making process and drive innovative treatment strategies. We have created and implemented MOSAIC, an artificial intelligence (AI)–based framework designed for multimodal analysis, classification, and personalized prognostic assessment in rare cancers. Clinical validation was performed on myelodysplastic syndrome (MDS), a rare hematologic cancer with clinical and genomic heterogeneities. METHODS: We analyzed 4,427 patients with MDS divided into training and validation cohorts. Deep learning methods were applied to integrate and impute clinical/genomic features. Clustering was performed by combining Uniform Manifold Approximation and Projection for Dimension Reduction + Hierarchical Density-Based Spatial Clustering of Applications with Noise (UMAP + HDBSCAN) methods, compared with the conventional Hierarchical Dirichlet Process (HDP). Linear and AI-based nonlinear approaches were compared for survival prediction. Explainable AI (Shapley Additive Explanations approach [SHAP]) and federated learning were used to improve the interpretation and the performance of the clinical models, integrating them into distributed infrastructure. RESULTS: UMAP + HDBSCAN clustering obtained a more granular patient stratification, achieving a higher average silhouette coefficient (0.16) with respect to HDP (0.01) and higher balanced accuracy in cluster classification by Random Forest (92.7% ± 1.3% and 85.8% ± 0.8%). AI methods for survival prediction outperform conventional statistical techniques and the reference prognostic tool for MDS. Nonlinear Gradient Boosting Survival stands in the internal (Concordance-Index [C-Index], 0.77; SD, 0.01) and external validation (C-Index, 0.74; SD, 0.02). SHAP analysis revealed that similar features drove patients' subgroups and outcomes in both training and validation cohorts. Federated implementation improved the accuracy of developed models. CONCLUSION: MOSAIC provides an explainable and robust framework to optimize classification and prognostic assessment of rare cancers. AI-based approaches demonstrated superior accuracy in capturing genomic similarities and providing individual prognostic information compared with conventional statistical methods. Its federated implementation ensures broad clinical application, guaranteeing high performance and data protection.

We study a wireless sensor network using CSMA/CA in the MAC layer under a backoff attack: some of the sensors of the network are malicious and deviate from the defined contention mechanism. We use Bianchi’s network model to study the impact of the malicious sensors on the total network throughput, showing that it causes the throughput to be unfairly distributed among sensors. We model this conflict using game theory tools, where each sensor is a player. We obtain analytical solutions and propose an algorithm, based on Regret Matching, to learn the equilibrium of the game with an arbitrary number of players. Our approach is validated via simulations, showing that our theoretical predictions adjust to reality.

The recent advances in Deep Learning have a significant impact on the security of wireless networks, such as intelligent attackers which are able to successfully exploit a possibly unknown defense mechanism simply by interacting with it. Their capacity of adapting to standard defense mechanisms, such as statistical tests, make them a significant threat. In this paper, we develop two intelligent defense mechanisms using inverse reinforcement learning tools, that can be used to enhance the capabilities of current defense mechanisms. We test our proposal on a backoff attack setup against an intelligent attacker, obtaining very significant gains in the defense performance.