Interpretable machine learning has emerged as central in leveraging artificial intelligence within high-stakes domains such as healthcare, where understanding the rationale behind model predictions is as critical as achieving high predictive accuracy. In this context, feature selection assumes a pivotal role in enhancing model interpretability by identifying the most important input features in black-box models. While random forests are frequently used in biomedicine for their remarkable performance on tabular datasets, the accuracy gained from aggregating decision trees comes at the expense of interpretability. Consequently, feature selection for enhancing interpretability in random forests has been extensively explored in supervised settings. However, its investigation in the unsupervised regime remains notably limited. To address this gap, the study introduces novel methods to construct feature graphs from unsupervised random forests and feature selection strategies to derive effective feature combinations from these graphs. Feature graphs are constructed for the entire dataset as well as individual clusters leveraging the parent-child node splits within the trees, such that feature centrality captures their relevance to the clustering task, while edge weights reflect the discriminating power of feature pairs. Graph-based feature selection methods are extensively evaluated on synthetic and benchmark datasets both in terms of their ability to reduce dimensionality while improving clustering performance, as well as to enhance model interpretability. An application on omics data for disease subtyping identifies the top features for each cluster, showcasing the potential of the proposed approach to enhance interpretability in clustering analyses and its utility in a real-world biomedical application.

In the realm of precision medicine, effective patient stratification and disease subtyping demand innovative methodologies tailored for multi-omics data. Clustering techniques applied to multi-omics data have become instrumental in identifying distinct subgroups of patients, enabling a finer-grained understanding of disease variability. This work establishes a powerful framework for advancing precision medicine through unsupervised random-forest-based clustering and federated computing. We introduce a novel multi-omics clustering approach utilizing unsupervised random-forests. The unsupervised nature of the random forest enables the determination of cluster-specific feature importance, unraveling key molecular contributors to distinct patient groups. Moreover, our methodology is designed for federated execution, a crucial aspect in the medical domain where privacy concerns are paramount. We have validated our approach on machine learning benchmark data sets as well as on cancer data from The Cancer Genome Atlas (TCGA). Our method is competitive with the state-of-the-art in terms of disease subtyping, but at the same time substantially improves the cluster interpretability. Experiments indicate that local clustering performance can be improved through federated computing.

Evaluating explanations of image classifiers regarding ground truth, e.g. segmentation masks defined by human perception, primarily evaluates the quality of the models under consideration rather than the explanation methods themselves. Driven by this observation, we propose a framework for $\textit{jointly}$ evaluating the robustness of safety-critical systems that $\textit{combine}$ a deep neural network with an explanation method. These are increasingly used in real-world applications like medical image analysis or robotics. We introduce a fine-tuning procedure to (mis)align model$\unicode{x2013}$explanation pipelines with ground truth and use it to quantify the potential discrepancy between worst and best-case scenarios of human alignment. Experiments across various model architectures and post-hoc local interpretation methods provide insights into the robustness of vision transformers and the overall vulnerability of such AI systems to potential adversarial attacks.

Explainable AI (XAI) is an increasingly important area of machine learning research, which aims to make black-box models transparent and interpretable. In this paper, we propose a novel approach to XAI that uses the so-called counterfactual paths generated by conditional permutations of features. The algorithm measures feature importance by identifying sequential permutations of features that most influence changes in model predictions. It is particularly suitable for generating explanations based on counterfactual paths in knowledge graphs incorporating domain knowledge. Counterfactual paths introduce an additional graph dimension to current XAI methods in both explaining and visualizing black-box models. Experiments with synthetic and medical data demonstrate the practical applicability of our approach.

Random Forests are powerful ensemble learning algorithms widely used in various machine learning tasks. However, they have a tendency to overfit noisy or irrelevant features, which can result in decreased generalization performance. Post-hoc regularization techniques aim to mitigate this issue by modifying the structure of the learned ensemble after its training. Here, we propose Bayesian post-hoc regularization to leverage the reliable patterns captured by leaf nodes closer to the root, while potentially reducing the impact of more specific and potentially noisy leaf nodes deeper in the tree. This approach allows for a form of pruning that does not alter the general structure of the trees but rather adjusts the influence of leaf nodes based on their proximity to the root node. We have evaluated the performance of our method on various machine learning data sets. Our approach demonstrates competitive performance with the state-of-the-art methods and, in certain cases, surpasses them in terms of predictive accuracy and generalization.

Clinical information systems have become large repositories for semi-structured and partly annotated electronic health record data, which have reached a critical mass that makes them interesting for supervised data-driven neural network approaches. We explored automated coding of 50 character long clinical problem list entries using the International Classification of Diseases (ICD-10) and evaluated three different types of network architectures on the top 100 ICD-10 three-digit codes. A fastText baseline reached a macro-averaged F1-score of 0.83, followed by a character-level LSTM with a macro-averaged F1-score of 0.84. The top performing approach used a downstreamed RoBERTa model with a custom language model, yielding a macro-averaged F1-score of 0.88. A neural network activation analysis together with an investigation of the false positives and false negatives unveiled inconsistent manual coding as a main limiting factor.

Network-based algorithms are used in most domains of research and industry in a wide variety of applications and are of great practical use. In this work, we demonstrate subnetwork detection based on multi-modal node features using a new Greedy Decision Forest for better interpretability. The latter will be a crucial factor in retaining experts and gaining their trust in such algorithms in the future. To demonstrate a concrete application example, we focus in this paper on bioinformatics and systems biology with a special focus on biomedicine. However, our methodological approach is applicable in many other domains as well. Systems biology serves as a very good example of a field in which statistical data-driven machine learning enables the analysis of large amounts of multi-modal biomedical data. This is important to reach the future goal of precision medicine, where the complexity of patients is modeled on a system level to best tailor medical decisions, health practices and therapies to the individual patient. Our glass-box approach could help to uncover disease-causing network modules from multi-omics data to better understand diseases such as cancer.