Evaluating Machine Learning Models against Clinical Protocols for Enhanced Interpretability and Continuity of Care

In clinical practice, decision-making relies heavily on established protocols, often formalised as rules. Concurrently, Machine Learning (ML) models, trained on clinical data, aspire to integrate into medical decision-making processes. However, despite the growing number of ML applications, their adoption into clinical practice remains limited. Two critical concerns arise, relevant to the notions of consistency and continuity of care: (a) accuracy - the ML model, albeit more accurate, might introduce errors that would not have occurred by applying the protocol; (b) interpretability - ML models operating as black boxes might make predictions based on relationships that contradict established clinical knowledge. In this context, the literature suggests using ML models integrating domain knowledge for improved accuracy and interpretability. However, there is a lack of appropriate metrics for comparing ML models with clinical rules in addressing these challenges. Accordingly, in this article, we first propose metrics to assess the accuracy of ML models with respect to the established protocol. Secondly, we propose an approach to measure the distance of explanations provided by two rule sets, with the goal of comparing the explanation similarity between clinical rule-based systems and rules extracted from ML models. The approach is validated on the Pima Indians Diabetes dataset by training two neural networks - one exclusively on data, and the other integrating a clinical protocol. Our findings demonstrate that the integrated ML model achieves comparable performance to that of a fully data-driven model while exhibiting superior accuracy relative to the clinical protocol, ensuring enhanced continuity of care. Furthermore, we show that our integrated model provides explanations for predictions that align more closely with the clinical protocol compared to the data-driven model.

Feature graphs for interpretable unsupervised tree ensembles: centrality, interaction, and application in disease subtyping

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.

Federated unsupervised random forest for privacy-preserving patient stratification

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.