Building trustworthy machine learning algorithms for biological applications requires adapting to data heterogeneity from different sources, batches, distributions, or studies. We propose the 'Cross-Cluster Weighted Forest' (CCWF), an ensembling approach that explicitly leverages heterogeneity in the feature distribution to produce more accurate and more generalizable predictors than the standard Random Forest in cases when data can be naturally clustered. CCWF generalizes the RF architecture to an outer unsupervised layer, supervised subtasks, and ensembling. Specifically it involves unsupervised clustering of the training data, fitting a Random Forest on each cluster, and combining the forests via stacked regression weights that reward cross-cluster generalizability. We provide a theoretical analysis of an analytically tractable forest model showing that cluster-based ensembling is asymptotically more accurate than training a single forest on the full data, with the gain driven by bias reduction. In simulations, we find that CCWF is robust across data-generating regimes and outcome models; furthermore, we explore the influence of data partitioning and ensemble weighting strategies on the benefits of our method. Finally, we apply our approach to cancer molecular profiling and gene expression datasets that are naturally divisible into clusters; in both simulations and real data examples, we illustrate that our approach outperforms classic Random Forest by margins of 30-40%, aligning with our theoretical results. Overall, we show that CCWF provides a statistically grounded prediction algorithm for data spanning multiple domains or sub-populations, a structure common in biological applications.
Multi-center survival prediction can improve robustness and generalizability, yet privacy regulations and institutional governance often prevent pooling patient-level clinical and genomic data across institutions. In practice, deployment is further complicated by feature-space heterogeneity, in which sites collect different covariates or use different sequencing panels, resulting in only partially overlapping feature sets. We present FederatedRSF, a Python package that implements federated random survival forests, aggregating locally trained survival trees and redistributing only feature-compatible trees to each site, enabling inference with partial overlap without sharing raw data. We evaluate FederatedRSF on the GBSG2 breast cancer cohort distributed with the scikit-survival package, simulating feature heterogeneity across clients by withholding subsets of features, and assessing discrimination using Harrell's concordance index (C-Index) under repeated cross-validation and site-splits. The results demonstrated that the federated model can achieve performance comparable to that of the centralized training setting.
Maryam Moradpour, Jonas Harriehausen, Amirreza Aleyasin +3
Swarm Learning is a decentralized collaborative learning mechanism that allows multiple organizations to train a shared model without central coordination or direct data sharing. In typical horizontal Swarm Learning, datasets across sites are usually assumed to share the same feature set. However, in real-world applications, sites often have partially overlapping features because measurements, protocols, and available covariates differ across sites. This feature heterogeneity creates a practical issue for machine learning algorithms such as Random Forests. Specifically, when decision trees are pooled into a global Random Forest, inference at a given site can become ill-defined if a traversal encounters a split on a feature that is not available locally, often forcing organizations to discard site-specific variables upfront. In this paper, we address feature heterogeneity in Swarm Learning with Random Forests under partially overlapping feature spaces. We propose several deterministic and probabilistic inference-time strategies that resolve such missing splits without restricting training to the intersection of features. We evaluate the methods on nine datasets and demonstrate that they outperform both the intersection baseline and locally trained models across a broad range of scenarios.
Counterfactual explanations provide local, interpretable insight by identifying changes to an input that would alter its assigned outcome. Although well established in supervised learning, their extension to clustering is less direct, since cluster assignments are unlabeled and governed by the geometry of the partition. This paper introduces VoICE, a Voronoi-Induced Counterfactual Explainability framework for feature-weighted k-means clustering. Rather than treating cluster change as a crossing of a single pairwise centroid boundary, VoICE formulates counterfactual generation as projection onto the full weighted Voronoi region of a target cluster, incorporating feature weights directly into both the clustering geometry and the counterfactual objective to yield least-cost and parsimonious explanations under actionability constraints. Target regions are further intersected with data-derived bounds and homothetically contracted towards their centroids, limiting extrapolation and boundary sensitivity. VoICE consistently produces valid target-cluster membership, across several benchmark datasets, where the leading pairwise baseline does not.