arXiv subjects

Livio Finos

Publications and source records attributed to Livio Finos.

At least 19 recordsLinked to original sources

arXiv2026

Robust confidence intervals for generalized linear models

Reliable uncertainty quantification is a central challenge in the analysis of modern biomedical data, where complex sources of variability often violate standard modeling assumptions. In generalized linear models (GLMs), confidence intervals for regression parameters provide such information, but they typically rely on correct specification of the mean-variance relationship. However, overdispersion, heteroskedasticity, and unobserved biological variability can lead to substantial undercoverage in practice. We propose a method for constructing confidence intervals that remains valid under variance misspecification. The approach is based on the inversion of hypothesis tests obtained by sign-flipping individual score contributions and uses a bisection algorithm to determine the interval bounds. The resulting intervals inherit robustness properties from the underlying tests, and we establish their asymptotic validity under general variance misspecification. Through simulation studies, we show that the proposed method achieves reliable coverage and outperforms standard Wald-type intervals when model assumptions are violated. We illustrate the approach in a differential expression analysis of RNA-sequencing data from a cancer study, where heterogeneous variability is pervasive and parametric methods can yield inconsistent inference. The proposed framework provides a practical and robust alternative to conventional quasi-likelihood or Wald-based methods for interval estimation in GLMs, particularly suited to high-throughput biomedical applications.

stat.ME↗

arXiv2026

Multivariate mixed models with model-free random effects

Linear mixed models are widely used to analyze non-independent data, but inference for fixed effects can be unreliable under misspecification of the random-effects distribution, inaccurate Fisher information estimation, or convergence failures, leading to a lack of control over false positives. These difficulties are amplified in multivariate settings, where within-cluster and between-response dependence must be modeled jointly. We propose a testing procedure for fixed effects in multivariate linear mixed models that avoids Fisher information estimation and does not require correct specification of the random-effects distribution by combining score statistics with clusterwise sign-flipping transformations. Our method accommodates both forms of dependence and yields asymptotically valid inference under weak distributional assumptions on the data-generating process.

stat.ME↗

arXiv2025

The role of data partitioning on the performance of EEG-based deep learning models in supervised cross-subject analysis: a preliminary study

Deep learning is significantly advancing the analysis of electroencephalography (EEG) data by effectively discovering highly nonlinear patterns within the signals. Data partitioning and cross-validation are crucial for assessing model performance and ensuring study comparability, as they can produce varied results and data leakage due to specific signal properties (e.g., biometric). Such variability leads to incomparable studies and, increasingly, overestimated performance claims, which are detrimental to the field. Nevertheless, no comprehensive guidelines for proper data partitioning and cross-validation exist in the domain, nor is there a quantitative evaluation of their impact on model accuracy, reliability, and generalizability. To assist researchers in identifying optimal experimental strategies, this paper thoroughly investigates the role of data partitioning and cross-validation in evaluating EEG deep learning models. Five cross-validation settings are compared across three supervised cross-subject classification tasks (BCI, Parkinson's, and Alzheimer's disease detection) and four established architectures of increasing complexity (ShallowConvNet, EEGNet, DeepConvNet, and Temporal-based ResNet). The comparison of over 100,000 trained models underscores, first, the importance of using subject-based cross-validation strategies for evaluating EEG deep learning models, except when within-subject analyses are acceptable (e.g., BCI). Second, it highlights the greater reliability of nested approaches (N-LNSO) compared to non-nested counterparts, which are prone to data leakage and favor larger models overfitting to validation data. In conclusion, this work provides EEG deep learning researchers with an analysis of data partitioning and cross-validation and offers guidelines to avoid data leakage, currently undermining the domain with potentially overestimated performance claims.

eess.SP↗

arXiv2025

Robust Inference for Generalized Linear Mixed Models: An Approach Based on Score Sign Flipping

Despite the versatility of generalized linear mixed models in handling complex experimental designs, they often suffer from misspecification and convergence problems. This makes inference on the values of coefficients problematic. To address these challenges, we propose a robust extension of the score-based statistical test using sign-flipping transformations. Our approach efficiently handles within-variance structure and heteroscedasticity, ensuring accurate regression coefficient testing. The approach is illustrated by analyzing the reduction of health issues over time for newly adopted children. The model is characterized by a binomial response with unbalanced frequencies and several categorical and continuous predictors. The proposed approach efficiently deals with critical problems related to longitudinal nonlinear models, surpassing common statistical approaches such as generalized estimating equations and generalized linear mixed models.

stat.ME↗

arXiv2025

HistoSmith: Single-Stage Histology Image-Label Generation via Conditional Latent Diffusion for Enhanced Cell Segmentation and Classification

Precise segmentation and classification of cell instances are vital for analyzing the tissue microenvironment in histology images, supporting medical diagnosis, prognosis, treatment planning, and studies of brain cytoarchitecture. However, the creation of high-quality annotated datasets for training remains a major challenge. This study introduces a novel single-stage approach (HistoSmith) for generating image-label pairs to augment histology datasets. Unlike state-of-the-art methods that utilize diffusion models with separate components for label and image generation, our approach employs a latent diffusion model to learn the joint distribution of cellular layouts, classification masks, and histology images. This model enables tailored data generation by conditioning on user-defined parameters such as cell types, quantities, and tissue types. Trained on the Conic H&E histopathology dataset and the Nissl-stained CytoDArk0 dataset, the model generates realistic and diverse labeled samples. Experimental results demonstrate improvements in cell instance segmentation and classification, particularly for underrepresented cell types like neutrophils in the Conic dataset. These findings underscore the potential of our approach to address data scarcity challenges.

cs.CV↗

arXiv2025

CISCA and CytoDArk0: a Cell Instance Segmentation and Classification method for histo(patho)logical image Analyses and a new, open, Nissl-stained dataset for brain cytoarchitecture studies

Delineating and classifying individual cells in microscopy tissue images is inherently challenging yet remains essential for advancements in medical and neuroscientific research. In this work, we propose a new deep learning framework, CISCA, for automatic cell instance segmentation and classification in histological slices. At the core of CISCA is a network architecture featuring a lightweight U-Net with three heads in the decoder. The first head classifies pixels into boundaries between neighboring cells, cell bodies, and background, while the second head regresses four distance maps along four directions. The outputs from the first and second heads are integrated through a tailored post-processing step, which ultimately produces the segmentation of individual cells. The third head enables the simultaneous classification of cells into relevant classes, if required. We demonstrate the effectiveness of our method using four datasets, including CoNIC, PanNuke, and MoNuSeg, which are publicly available H&Estained datasets that cover diverse tissue types and magnifications. In addition, we introduce CytoDArk0, the first annotated dataset of Nissl-stained histological images of the mammalian brain, containing nearly 40k annotated neurons and glia cells, aimed at facilitating advancements in digital neuropathology and brain cytoarchitecture studies. We evaluate CISCA against other state-of-the-art methods, demonstrating its versatility, robustness, and accuracy in segmenting and classifying cells across diverse tissue types, magnifications, and staining techniques. This makes CISCA well-suited for detailed analyses of cell morphology and efficient cell counting in both digital pathology workflows and brain cytoarchitecture research.

eess.IV↗

arXiv2025

Mind the Gap: Evaluating Patch Embeddings from General-Purpose and Histopathology Foundation Models for Cell Segmentation and Classification

Recent advancements in foundation models have transformed computer vision, driving significant performance improvements across diverse domains, including digital histopathology. However, the advantages of domain-specific histopathology foundation models over general-purpose models for specialized tasks such as cell analysis remain underexplored. This study investigates the representation learning gap between these two categories by analyzing multi-level patch embeddings applied to cell instance segmentation and classification. We implement an encoder-decoder architecture with a consistent decoder and various encoders. These include convolutional, vision transformer (ViT), and hybrid encoders pre-trained on ImageNet-22K or LVD-142M, representing general-purpose foundation models. These are compared against ViT encoders from the recently released UNI, Virchow2, and Prov-GigaPath foundation models, trained on patches extracted from hundreds of thousands of histopathology whole-slide images. The decoder integrates patch embeddings from different encoder depths via skip connections to generate semantic and distance maps. These maps are then post-processed to create instance segmentation masks where each label corresponds to an individual cell and to perform cell-type classification. All encoders remain frozen during training to assess their pre-trained feature extraction capabilities. Using the PanNuke and CoNIC histopathology datasets, and the newly introduced Nissl-stained CytoDArk0 dataset for brain cytoarchitecture studies, we evaluate instance-level detection, segmentation accuracy, and cell-type classification. This study provides insights into the comparative strengths and limitations of general-purpose vs. histopathology foundation models, offering guidance for model selection in cell-focused histopathology and brain cytoarchitecture analysis workflows.

cs.CV↗

arXiv2024

Automated Classification of Cell Shapes: A Comparative Evaluation of Shape Descriptors

This study addresses the challenge of classifying cell shapes from noisy contours, such as those obtained through cell instance segmentation of histological images. We assess the performance of various features for shape classification, including Elliptical Fourier Descriptors, curvature features, and lower dimensional representations. Using an annotated synthetic dataset of noisy contours, we identify the most suitable shape descriptors and apply them to a set of real images for qualitative analysis. Our aim is to provide a comprehensive evaluation of descriptors for classifying cell shapes, which can support cell type identification and tissue characterization-critical tasks in both biological research and histopathological assessments.

cs.CV↗

arXiv2024

Conformal inference for cell type annotation with graph-structured constraints

Conformal prediction is a framework for constructing prediction sets for machine learning models, relying solely on the exchangeability of training and test data and without requiring to specify a parametric distribution. Despite its wide applicability and popularity, its application in single-cell transcriptomics remains underexplored. This paper addresses this gap by developing an approach that leverages the rich information about cell-type relations, encoded in the graph structure of cell ontologies, to enhance the interpretability of reference-based cell-type annotation. Leveraging conformal risk control, we develop a novel conformal algorithm for graph-structured predictions and we demonstrate how incorporating graph constraints can improve the interpretation of cell-type predictions. This approach aims to generate more coherent conformal sets that align with the inherent relationships among classes, facilitating clearer and more intuitive interpretations of model predictions. Additionally, we provide a technique to address non-exchangeability, particularly when the cell-type distribution changes between training and test datasets. We implemented our method in the open-source R package scConform, available at https://bioconductor.posit.co/packages/release/bioc/html/scConform.html.

stat.ME↗

arXiv2024

Permutation-based multiple testing when fitting many generalized linear models

In many applied sciences a popular analysis strategy for high-dimensional data is to fit many multivariate generalized linear models in parallel. This paper presents a novel approach to address the resulting multiple testing problem by combining a recently developed sign-flip test with permutation-based multiple-testing procedures. Our method builds upon the univariate standardized flip-scores test which offers robustness against misspecified variances in generalized linear models, a crucial feature in high-dimensional settings where comprehensive model validation is particularly challenging. We extend this approach to the multivariate setting, enabling adaptation to unknown response correlation structures. This approach yields relevant power improvements over conventional multiple testing methods when correlation is present.

math.ST↗

arXiv2024

Inference in generalized linear models with robustness to misspecified variances

Generalized linear models usually assume a common dispersion parameter, an assumption that is seldom true in practice. Consequently, standard parametric methods may suffer appreciable loss of type I error control. As an alternative, we present a semi-parametric group-invariance method based on sign flipping of score contributions. Our method requires only the correct specification of the mean model, but is robust against any misspecification of the variance. We present tests for single as well as multiple regression coefficients. The test is asymptotically valid but shows excellent performance in small samples. We illustrate the method using RNA sequencing count data, for which it is difficult to model the overdispersion correctly. The method is available in the R library flipscores.

stat.ME↗

arXiv2024

A novel CFA+EFA model to detect aberrant respondents

Aberrant respondents are common but yet extremely detrimental to the quality of social surveys or questionnaires. Recently, factor mixture models have been employed to identify individuals providing deceptive or careless responses. We propose a comprehensive factor mixture model for continuous outcomes that combines confirmatory and exploratory factor models to classify both the non-aberrant and aberrant respondents. The flexibility of the proposed {classification model} allows for the identification of two of the most common aberrant response styles, namely faking and careless responding. We validated our approach by means of two simulations and two case studies. The results indicate the effectiveness of the proposed model in dealing with aberrant responses in social and behavioural surveys.

stat.ME↗

arXiv2023

Revealing Cortical Layers In Histological Brain Images With Self-Supervised Graph Convolutional Networks Applied To Cell-Graphs

Identifying cerebral cortex layers is crucial for comparative studies of the cytoarchitecture aiming at providing insights into the relations between brain structure and function across species. The absence of extensive annotated datasets typically limits the adoption of machine learning approaches, leading to the manual delineation of cortical layers by neuroanatomists. We introduce a self-supervised approach to detect layers in 2D Nissl-stained histological slices of the cerebral cortex. It starts with the segmentation of individual cells and the creation of an attributed cell-graph. A self-supervised graph convolutional network generates cell embeddings that encode morphological and structural traits of the cellular environment and are exploited by a community detection algorithm for the final layering. Our method, the first self-supervised of its kind with no spatial transcriptomics data involved, holds the potential to accelerate cytoarchitecture analyses, sidestepping annotation needs and advancing cross-species investigation.

cs.CV↗

arXiv2023

NCIS: Deep Color Gradient Maps Regression and Three-Class Pixel Classification for Enhanced Neuronal Cell Instance Segmentation in Nissl-Stained Histological Images

Deep learning has proven to be more effective than other methods in medical image analysis, including the seemingly simple but challenging task of segmenting individual cells, an essential step for many biological studies. Comparative neuroanatomy studies are an example where the instance segmentation of neuronal cells is crucial for cytoarchitecture characterization. This paper presents an end-to-end framework to automatically segment single neuronal cells in Nissl-stained histological images of the brain, thus aiming to enable solid morphological and structural analyses for the investigation of changes in the brain cytoarchitecture. A U-Net-like architecture with an EfficientNet as the encoder and two decoding branches is exploited to regress four color gradient maps and classify pixels into contours between touching cells, cell bodies, or background. The decoding branches are connected through attention gates to share relevant features, and their outputs are combined to return the instance segmentation of the cells. The method was tested on images of the cerebral cortex and cerebellum, outperforming other recent deep-learning-based approaches for the instance segmentation of cells.

eess.IV↗

arXiv2023

Permutation-based true discovery proportions for functional Magnetic Resonance Imaging cluster analysis

We propose a permutation-based method for testing a large collection of hypotheses simultaneously. Our method provides lower bounds for the number of true discoveries in any selected subset of hypotheses. These bounds are simultaneously valid with high confidence. The methodology is particularly useful in functional Magnetic Resonance Imaging cluster analysis, where it provides a confidence statement on the percentage of truly activated voxels within clusters of voxels, avoiding the well-known spatial specificity paradox. We offer a user-friendly tool to estimate the percentage of true discoveries for each cluster while controlling the family-wise error rate for multiple testing and taking into account that the cluster was chosen in a data-driven way. The method adapts to the spatial correlation structure that characterizes functional Magnetic Resonance Imaging data, gaining power over parametric approaches.

stat.AP↗

arXiv2023

Permutation-Based True Discovery Guarantee by Sum Tests

Sum-based global tests are highly popular in multiple hypothesis testing. In this paper we propose a general closed testing procedure for sum tests, which provides lower confidence bounds for the proportion of true discoveries (TDP), simultaneously over all subsets of hypotheses. These simultaneous inferences come for free, i.e., without any adjustment of the alpha-level, whenever a global test is used. Our method allows for an exploratory approach, as simultaneity ensures control of the TDP even when the subset of interest is selected post hoc. It adapts to the unknown joint distribution of the data through permutation testing. Any sum test may be employed, depending on the desired power properties. We present an iterative shortcut for the closed testing procedure, based on the branch and bound algorithm, which converges to the full closed testing results, often after few iterations; even if it is stopped early, it controls the TDP. We compare the properties of different choices for the sum test through simulations, then we illustrate the feasibility of the method for high dimensional data on brain imaging and genomics data.

stat.ME↗

arXiv2023

Procrustes-based distances for exploring between-matrices similarity

The statistical shape analysis called Procrustes analysis minimizes the distance between matrices by similarity transformations. The method returns a set of optimal orthogonal matrices, which project each matrix into a common space. This manuscript presents two types of distances derived from Procrustes analysis for exploring between-matrices similarity. The first one focuses on the residuals from the Procrustes analysis, i.e., the residual-based distance metric. In contrast, the second one exploits the fitted orthogonal matrices, i.e., the rotational-based distance metric. Thanks to these distances, similarity-based techniques such as the multidimensional scaling method can be applied to visualize and explore patterns and similarities among observations. The proposed distances result in being helpful in functional magnetic resonance imaging (fMRI) data analysis. The brain activation measured over space and time can be represented by a matrix. The proposed distances applied to a sample of subjects -- i.e., matrices -- revealed groups of individuals sharing patterns of neural brain activation.

stat.AP↗

arXiv2022

MR-NOM: Multi-scale Resolution of Neuronal cells in Nissl-stained histological slices via deliberate Over-segmentation and Merging

In comparative neuroanatomy, the characterization of brain cytoarchitecture is critical to a better understanding of brain structure and function, as it helps to distill information on the development, evolution, and distinctive features of different populations. The automatic segmentation of individual brain cells is a primary prerequisite and yet remains challenging. A new method (MR-NOM) was developed for the instance segmentation of cells in Nissl-stained histological images of the brain. MR-NOM exploits a multi-scale approach to deliberately over-segment the cells into superpixels and subsequently merge them via a classifier based on shape, structure, and intensity features. The method was tested on images of the cerebral cortex, proving successful in dealing with cells of varying characteristics that partially touch or overlap, showing better performance than two state-of-the-art methods.

eess.IV↗