A multiverse-consensus pipeline for reproducible feature selection in untargeted LC-MS metabolomics

Background: Untargeted LC-MS metabolomics requires a long chain of preprocessing decisions, each with several equally defensible options. Analysts typically commit to one pipeline and report the resulting feature shortlist. How strongly that shortlist depends on choices that were never varied stays invisible. Results: We adapt multiverse analysis to untargeted metabolomics feature selection. We present an auditable, configuration-driven pipeline that (i) applies a ten-stage quality-control filter cascade in which every feature's fate is logged, and (ii) runs the downstream analysis as a multiverse over four contrasting preprocessing philosophies, each combined with four feature-ranking methods under bootstrap stability selection and label-permutation testing. Only features recurring across paths enter a tiered consensus. On a demonstration dataset of five breast-cancer cell lines (30,370 detected features), the four single pipelines individually returned shortlists of 4-20 features whose pairwise agreement was as low as Jaccard = 0.05. The multiverse consensus retained 15 features (>=2/4 paths), of which one recurred across all four, although two paths (sharing normalization and drift-correction methods) dominate the consensus. A pipeline-wide label-permutation test found no false discoveries in 50 null permutations. Conclusions: Reporting only preprocessing-robust features, with a complete kept/dropped audit trail, converts hidden analytical degrees of freedom into an explicit, inspectable output. We discuss scope and limitations, including single-batch design and the need for independent validation.

RobustModelMaker: Coupling Bootstrap Stability Selection with Leakage-Safe Nested Cross-Validation for Scientific Machine Learning

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.

2D Stability Selection: Design Jittering for Doubly Stable Feature Selection

We study feature selection in high-dimensional regression under two distinct sources of instability: sampling variability and measurement error in the design matrix. Stability Selection addresses the former through sub-sampling and aggregation, but does not explicitly stress-test robustness to noisy predictors. We introduce doubly stable feature selection, a perturb-and-aggregate framework that targets features whose inclusion is stable both across randomization and across increasing levels of design noise. The method injects controlled additive noise into the design matrix, fits a fixed base selector such as the Lasso on the perturbed data, and aggregates selection frequencies. Sweeping over a grid of noise levels yields a stability path that summarizes robustness to measurement error while using the full sample size and isolating the effect of design perturbations. On the theory side, we show that classical model-selection conditions are preserved under sufficiently small perturbations, with a high-probability extension for Gaussian noise. Empirically, experiments on synthetic and real datasets show improved robustness compared with Stability Selection and standard base selectors.