A graph neural network-based model with Out-of-Distribution Robustness for enhancing Antiretroviral Therapy Outcome Prediction for HIV-1

Predicting the outcome of antiretroviral therapies for HIV-1 is a pressing clinical challenge, especially when the treatment regimen includes drugs for which limited effectiveness data is available. This scarcity of data can arise either due to the introduction of a new drug to the market or due to limited use in clinical settings. To tackle this issue, we introduce a novel joint fusion model, which combines features from a Fully Connected (FC) Neural Network and a Graph Neural Network (GNN). The FC network employs tabular data with a feature vector made up of viral mutations identified in the most recent genotypic resistance test, along with the drugs used in therapy. Conversely, the GNN leverages knowledge derived from Stanford drug-resistance mutation tables, which serve as benchmark references for deducing in-vivo treatment efficacy based on the viral genetic sequence, to build informative graphs. We evaluated these models' robustness against Out-of-Distribution drugs in the test set, with a specific focus on the GNN's role in handling such scenarios. Our comprehensive analysis demonstrates that the proposed model consistently outperforms the FC model, especially when considering Out-of-Distribution drugs. These results underscore the advantage of integrating Stanford scores in the model, thereby enhancing its generalizability and robustness, but also extending its utility in real-world applications with limited data availability. This research highlights the potential of our approach to inform antiretroviral therapy outcome prediction and contribute to more informed clinical decisions.

Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1

Motivation: In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables. We compare a model encompassing history (H) with one not using it (NH). Results: The H-model demonstrates superior discriminative ability, with a higher ROC-AUC score (76.34%) than the NH-model (74.98%). Significant Wilcoxon test results confirm that incorporating historical information improves consistently predictive accuracy for treatment outcomes. The better performance of the H-model might be attributed to its consideration of latent HIV reservoirs, probably obtained when leveraging historical information. The findings emphasize the importance of temporal dynamics in mutations, offering insights into HIV infection complexities. However, our result also shows that prediction accuracy remains relatively high even when no historical information is available. Supplementary information: Supplementary material is available.

Unboxing Tree Ensembles for interpretability: a hierarchical visualization tool and a multivariate optimal re-built tree

The interpretability of models has become a crucial issue in Machine Learning because of algorithmic decisions' growing impact on real-world applications. Tree ensemble methods, such as Random Forests or XgBoost, are powerful learning tools for classification tasks. However, while combining multiple trees may provide higher prediction quality than a single one, it sacrifices the interpretability property resulting in "black-box" models. In light of this, we aim to develop an interpretable representation of a tree-ensemble model that can provide valuable insights into its behavior. First, given a target tree-ensemble model, we develop a hierarchical visualization tool based on a heatmap representation of the forest's feature use, considering the frequency of a feature and the level at which it is selected as an indicator of importance. Next, we propose a mixed-integer linear programming (MILP) formulation for constructing a single optimal multivariate tree that accurately mimics the target model predictions. The goal is to provide an interpretable surrogate model based on oblique hyperplane splits, which uses only the most relevant features according to the defined forest's importance indicators. The MILP model includes a penalty on feature selection based on their frequency in the forest to further induce sparsity of the splits. The natural formulation has been strengthened to improve the computational performance of mixed-integer software. Computational experience is carried out on benchmark datasets from the UCI repository using a state-of-the-art off-the-shelf solver. Results show that the proposed model is effective in yielding a shallow interpretable tree approximating the tree-ensemble decision function.

AI-based Data Preparation and Data Analytics in Healthcare: The Case of Diabetes

The Associazione Medici Diabetologi (AMD) collects and manages one of the largest worldwide-available collections of diabetic patient records, also known as the AMD database. This paper presents the initial results of an ongoing project whose focus is the application of Artificial Intelligence and Machine Learning techniques for conceptualizing, cleaning, and analyzing such an important and valuable dataset, with the goal of providing predictive insights to better support diabetologists in their diagnostic and therapeutic choices.