ARISE: An adaptive residual-informed stability ensemble for feature selection in small-sample biomedical omics

Small-to-medium scientific datasets place machine learning pipelines under two compounding pressures. Single-run feature selection produces feature sets that change substantially under small perturbations of the training data, and any procedure that uses the same data for selection, tuning, and evaluation produces optimistically biased performance estimates. The two failure modes are routinely treated as separable, but in the regimes where scientific data live, they interact: an unstable selection inflates the variance of an already-optimistic score, and standard remedies for one rarely address the other. RobustModelMaker is a Python framework that couples bootstrap stability selection with strict nested cross-validation, performs all preprocessing and selection inside each fold, and produces a stability-tested feature subset together with a leakage-safe performance estimate. The framework supports nine algorithms across binary classification, multiclass classification, and regression. Behaviour is verified by a deterministic test suite spanning unit, performance, and reproducibility checks on three real scientific datasets comparing to three alternative selectors (ANOVA F-test, recursive feature elimination with cross-validation, and Boruta) on both predictive score and a Jaccard measure of selection stability. RobustModelMaker is competitive in score with the best alternative selector on each dataset, and occupies a position on the joint score-stability frontier that none of the alternatives match across all three task types. Two example applications, ovarian cancer biomarker discovery from the PLCO Trial and critical-temperature regression on the UCI Superconductivity Data, illustrate how the framework is used in practice and what trade-offs become visible when stability is treated as a first-class deliverable rather than an emergent property.

The high cost of functional molecular assays, and prevalence of missing modalities and unmatched samples in computational biology, create significant barriers to comprehensive multi-omic profiling, essential for capturing and reasoning over molecules, cells, tissues, and organisms. This work proposes a model that learns meaningful representations from multi-omics cancer data supporting the reconstruction of missing and unpaired modalities. Contrary to increasingly complex, larger models, e.g. Foundation Models (FMs), ARO prioritizes practical applicability in limited or incomplete data settings. ARO optimally reconstructs missing modalities (MSE of $0.15$ on the validation and test data in the Unmasked settings), with its learned latent embeddings enabling a downstream cancer classification task. Our findings indicate that analyzing diverse molecular layers as a single integrated system offers a reliable and cost-efficient approach, reducing dependence on large-scale experimental testing, while still supporting multi-omic exploration in limited data settings.

Selecting a subset of features (columns) from a tabular dataset is a ubiquitous challenge in real-world applications. Industry experts seek to minimize model training costs, climate scientists require an interpretable subset of factors to understand extreme weather events, and clinicians need to choose among diagnostic tests due to financial and time constraints. When looking at the scientific literature to determine which feature selection method to use, practitioners across domains face an unrepresentative landscape of benchmarking. Despite extensive research, existing feature selection benchmarks provide limited guidance because they rely on outdated models, ad hoc evaluation protocols, or artificially generated data that do not reflect real-world problems. To close the gap between scientific benchmarking and real-world applications, we introduce SelectArena, a modern benchmark for feature selection. We compare 15 widely used feature selection methods on 71 manually curated real-world tabular datasets, covering classification and regression problems, using standardized evaluation protocols and state-of-the-art tabular (foundation) models. Our results reveal clear trade-offs across predictive performance, runtime, stability, and validity. Tree-based methods, CART and RFImportance, along with F-Test are Pareto-optimal when taking into account predictive performance and runtime. F-Test, information-theory-, and distance-based methods lead on stability and validity, with F-Test emerging as a balanced choice across our metrics. Search-based methods are slow, unstable and achieve low performance. SelectArena turns these findings into practical guidance and, as an extensible platform, supports future feature selection research.