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Detecting Batch Heterogeneity via Likelihood Clustering

arXiv.org Machine Learning

Batch effects represent a major confounder in genomic diagnostics. In copy number variant (CNV) detection from NGS, many algorithms compare read depth between test samples and a reference sample, assuming they are process-matched. When this assumption is violated, with causes ranging from reagent lot changes to multi-site processing, the reference becomes inappropriate, introducing false CNV calls or masking true pathogenic variants. Detecting such heterogeneity before downstream analysis is critical for reliable clinical interpretation. Existing batch effect detection methods either cluster samples based on raw features, risking conflation of biological signal with technical variation, or require known batch labels that are frequently unavailable. We introduce a method that addresses both limitations by clustering samples according to their Bayesian model evidence. The central insight is that evidence quantifies compatibility between data and model assumptions, technical artifacts violate assumptions and reduce evidence, whereas biological variation, including CNV status, is anticipated by the model and yields high evidence. This asymmetry provides a discriminative signal that separates batch effects from biology. We formalize heterogeneity detection as a likelihood ratio test for mixture structure in evidence space, using parametric bootstrap calibration to ensure conservative false positive rates. We validate our approach on synthetic data demonstrating proper Type I error control, three clinical targeted sequencing panels (liquid biopsy, BRCA, and thalassemia) exhibiting distinct batch effect mechanisms, and mouse electrophysiology recordings demonstrating cross-modality generalization. Our method achieves superior clustering accuracy compared to standard correlation-based and dimensionality-reduction approaches while maintaining the conservativeness required for clinical usage.


LARGE: A Locally Adaptive Regularization Approach for Estimating Gaussian Graphical Models

arXiv.org Machine Learning

The graphical Lasso (GLASSO) is a widely used algorithm for learning high-dimensional undirected Gaussian graphical models (GGM). Given i.i.d. observations from a multivariate normal distribution, GLASSO estimates the precision matrix by maximizing the log-likelihood with an \ell_1-penalty on the off-diagonal entries. However, selecting an optimal regularization parameter λin this unsupervised setting remains a significant challenge. A well-known issue is that existing methods, such as out-of-sample likelihood maximization, select a single global λand do not account for heterogeneity in variable scaling or partial variances. Standardizing the data to unit variances, although a common workaround, has been shown to negatively affect graph recovery. Addressing the problem of nodewise adaptive tuning in graph estimation is crucial for applications like computational neuroscience, where brain networks are constructed from highly heterogeneous, region-specific fMRI data. In this work, we develop Locally Adaptive Regularization for Graph Estimation (LARGE), an approach to adaptively learn nodewise tuning parameters to improve graph estimation and selection. In each block coordinate descent step of GLASSO, we augment the nodewise Lasso regression to jointly estimate the regression coefficients and error variance, which in turn guides the adaptive learning of nodewise penalties. In simulations, LARGE consistently outperforms benchmark methods in graph recovery, demonstrates greater stability across replications, and achieves the best estimation accuracy in the most difficult simulation settings. We demonstrate the practical utility of our method by estimating brain functional connectivity from a real fMRI data set.


Constraint- and Score-Based Nonlinear Granger Causality Discovery with Kernels

arXiv.org Machine Learning

Granger causality (GC) [15] is a time series causal discovery framework that uses predictive modeling to identify the underlying causal structure of a time series system. Relying on the assumption that cause precedes effect, GC assesses whether including the lagged information from one time series in the autoregressive model of a second time series enhances its predictions. This improvement indicates a predictive relationship between the time series variables, where one time series provides supplemental information about the future of another time series, thereby signifying the presence of a (Granger) causal relationship. GC requires only observational data, and has been used for time series causal discovery across diverse domains, including climate science [33], political and social sciences [17], econometrics [4], and biological systems studies [13]. The original formulation of GC requires several assumptions to be satisfied for causal identifiability. In regards to the candidate time series system, it is assumed that the time series variables are stationary, and that all variables are observed (absence of latent confounders). GC was initially proposed for bivariate time series systems, but was generalised for the multivariate setting to accommodate the assumption that all relevant variables are included in the analysis [15]. Additional assumptions are made with regard to the types of causal relationships that can be identified within the time series system. GC cannot estimate a causal relationship between time series at an instantaneous time point, relying on the relationship between the lags and predicted values to determine a GC relationship.


Robust low-rank estimation with multiple binary responses using pairwise AUC loss

arXiv.org Machine Learning

Multiple binary responses arise in many modern data-analytic problems. Although fitting separate logistic regressions for each response is computationally attractive, it ignores shared structure and can be statistically inefficient, especially in high-dimensional and class-imbalanced regimes. Low-rank models offer a natural way to encode latent dependence across tasks, but existing methods for binary data are largely likelihood-based and focus on pointwise classification rather than ranking performance. In this work, we propose a unified framework for learning with multiple binary responses that directly targets discrimination by minimizing a surrogate loss for the area under the ROC curve (AUC). The method aggregates pairwise AUC surrogate losses across responses while imposing a low-rank constraint on the coefficient matrix to exploit shared structure. We develop a scalable projected gradient descent algorithm based on truncated singular value decomposition. Exploiting the fact that the pairwise loss depends only on differences of linear predictors, we simplify computation and analysis. We establish non-asymptotic convergence guarantees, showing that under suitable regularity conditions, leading to linear convergence up to the minimax-optimal statistical precision. Extensive simulation studies demonstrate that the proposed method is robust in challenging settings such as label switching and data contamination and consistently outperforms likelihood-based approaches.


Detecting LLM-Generated Text with Performance Guarantees

arXiv.org Machine Learning

Large language models (LLMs) such as GPT, Claude, Gemini, and Grok have been deeply integrated into our daily life. They now support a wide range of tasks -- from dialogue and email drafting to assisting with teaching and coding, serving as search engines, and much more. However, their ability to produce highly human-like text raises serious concerns, including the spread of fake news, the generation of misleading governmental reports, and academic misconduct. To address this practical problem, we train a classifier to determine whether a piece of text is authored by an LLM or a human. Our detector is deployed on an online CPU-based platform https://huggingface.co/spaces/stats-powered-ai/StatDetectLLM, and contains three novelties over existing detectors: (i) it does not rely on auxiliary information, such as watermarks or knowledge of the specific LLM used to generate the text; (ii) it more effectively distinguishes between human- and LLM-authored text; and (iii) it enables statistical inference, which is largely absent in the current literature. Empirically, our classifier achieves higher classification accuracy compared to existing detectors, while maintaining type-I error control, high statistical power, and computational efficiency.


Multi-task Modeling for Engineering Applications with Sparse Data

arXiv.org Machine Learning

Modern engineering and scientific workflows frequently require simultaneous prediction across related tasks and fidelity levels [1-6]. In such contexts, some outputs are scarce and expensive to obtain, while others are cheaper and more abundant. Multi-task Gaussian processes (MTGPs), also known as multi-output Gaussian processes, offer a principled Bayesian framework to exploit inter-task correlations, enabling knowledge sharing that improves predictive accuracy and reduces the demand for large high-fidelity datasets [7-9]. Over decades of development, MTGPs have been applied across diverse domains, including time series forecasting, multitask optimization, and multifidelity classification, demonstrating their broad utility wherever data cost asymmetries and cross-task dependencies are present [10-16]. The central motivation for MTGPs is to leverage dependencies among related tasks to enhance predictive quality when high-fidelity information is limited [17]. For example, predicting an airfoil's lift coefficient from limited, expensive high-fidelity computational fluid dynamics (CFD) simulations can benefit from correlating with sufficient low-fidelity simulations [3]. Recent work in joint multi-objective and multifidelity optimization has also utilized MT - GPs to balance exploration and exploitation across tasks, improving predictive performance and decision-making by explicitly modeling relationships among outputs and fidelities [12].


Multi-Group Quadratic Discriminant Analysis via Projection

arXiv.org Machine Learning

Multi-group classification arises in many prediction and decision-making problems, including applications in epidemiology, genomics, finance, and image recognition. Although classification methods have advanced considerably, much of the literature focuses on binary problems, and available extensions often provide limited flexibility for multi-group settings. Recent work has extended linear discriminant analysis to multiple groups, but more general methods are still needed to handle complex structures such as nonlinear decision boundaries and group-specific covariance patterns. We develop Multi-Group Quadratic Discriminant Analysis (MGQDA), a method for multi-group classification built on quadratic discriminant analysis. MGQDA projects high-dimensional predictors onto a lower-dimensional subspace, which enables accurate classification while capturing nonlinearity and heterogeneity in group-specific covariance structures. We derive theoretical guarantees, including variable selection consistency, to support the reliability of the procedure. In simulations and a gene-expression application, MGQDA achieves competitive or improved predictive performance compared with existing methods while selecting group-specific informative variables, indicating its practical value for high-dimensional multi-group classification problems. Supplementary materials for this article are available online.


ROOFS: RObust biOmarker Feature Selection

arXiv.org Machine Learning

Feature selection (FS) is essential for biomarker discovery and in the analysis of biomedical datasets. However, challenges such as high-dimensional feature space, low sample size, multicollinearity, and missing values make FS non-trivial. Moreover, FS performances vary across datasets and predictive tasks. We propose roofs, a Python package available at https://gitlab.inria.fr/compo/roofs, designed to help researchers in the choice of FS method adapted to their problem. Roofs benchmarks multiple FS methods on the user's data and generates reports that summarize a comprehensive set of evaluation metrics, including downstream predictive performance estimated using optimism correction, stability, reliability of individual features, and true positive and false positive rates assessed on semi-synthetic data with a simulated outcome. We demonstrate the utility of roofs on data from the PIONeeR clinical trial, aimed at identifying predictors of resistance to anti-PD-(L)1 immunotherapy in lung cancer. The PIONeeR dataset contained 374 multi-source blood and tumor biomarkers from 435 patients. A reduced subset of 214 features was obtained through iterative variance inflation factor pre-filtering. Of the 34 FS methods gathered in roofs, we evaluated 23 in combination with 11 classifiers (253 models in total) and identified a filter based on the union of Benjamini-Hochberg false discovery rate-adjusted p-values from t-test and logistic regression as the optimal approach, outperforming other methods including the widely used LASSO. We conclude that comprehensive benchmarking with roofs has the potential to improve the robustness and reproducibility of FS discoveries and increase the translational value of clinical models.


Aligned explanations in neural networks

arXiv.org Machine Learning

Feature attribution is the dominant paradigm for explaining deep neural networks. However, most existing methods only loosely reflect the model's prediction-making process, thereby merely white-painting the black box. We argue that explanatory alignment is a key aspect of trustworthiness in prediction tasks: explanations must be directly linked to predictions, rather than serving as post-hoc rationalizations. We present model readability as a design principle enabling alignment, and PiNets as a modeling framework to pursue it in a deep learning context. PiNets are pseudo-linear networks that produce instance-wise linear predictions in an arbitrary feature space, making them linearly readable. We illustrate their use on image classification and segmentation tasks, demonstrating how PiNets produce explanations that are faithful across multiple criteria in addition to alignment.


A Theoretical and Empirical Taxonomy of Imbalance in Binary Classification

arXiv.org Machine Learning

Class imbalance significantly degrades classification performance, yet its effects are rarely analyzed from a unified theoretical perspective. We propose a principled framework based on three fundamental scales: the imbalance coefficient $η$, the sample--dimension ratio $κ$, and the intrinsic separability $Δ$. Starting from the Gaussian Bayes classifier, we derive closed-form Bayes errors and show how imbalance shifts the discriminant boundary, yielding a deterioration slope that predicts four regimes: Normal, Mild, Extreme, and Catastrophic. Using a balanced high-dimensional genomic dataset, we vary only $η$ while keeping $κ$ and $Δ$ fixed. Across parametric and non-parametric models, empirical degradation closely follows theoretical predictions: minority Recall collapses once $\log(η)$ exceeds $Δ\sqrtκ$, Precision increases asymmetrically, and F1-score and PR-AUC decline in line with the predicted regimes. These results show that the triplet $(η,κ,Δ)$ provides a model-agnostic, geometrically grounded explanation of imbalance-induced deterioration.