arXiv subjects

Francesco Denti

Publications and source records attributed to Francesco Denti.

15 recordsLinked to original sources

arXiv2025

Spatially Regularized Gaussian Mixtures for Clustering Spatial Transcriptomic Data

Spatial transcriptomics measures the expression of thousands of genes in a tissue sample while preserving its spatial structure. This class of technologies has enabled the investigation of the spatial variation of gene expressions and their impact on specific biological processes. Identifying genes with similar expression profiles is of utmost importance, thus motivating the development of flexible methods leveraging spatial data structure to cluster genes. Here, we propose a modeling framework for clustering observations measured over numerous spatial locations via Gaussian processes. Rather than specifying their covariance kernels as a function of the spatial structure, we use it to inform a generalized Cholesky decomposition of their precision matrices. This approach prevents issues with kernel misspecification and facilitates the estimation of a non-stationarity spatial covariance structure. Applied to spatial transcriptomic data, our model identifies gene clusters with distinctive spatial correlation patterns across tissue areas comprising different cell types, like tumoral and stromal areas.

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arXiv2025

Multiomics Tissue Segmentation via Spatially-Informed Nested Biclustering Methods

Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging (MSI) is a powerful technique for spatially resolved molecular profiling and cancer biomarker discovery. Recent advances, including a novel multiomics workflow, enable multiple rounds of MSI on the same tissue section, extracting diverse molecular classes, e.g., lipids, peptides, and N-glycans, while preserving spatial resolution. This innovation is particularly valuable for studies with limited tissue sample availability, such as rare diseases or small tumors. However, the resulting data are high-dimensional, spatially structured, and the various molecular types share the same pixel grid. To address these challenges, we propose Poseidon, a Bayesian nonparametric nested biclustering model that simultaneously segments the common tissue pixels and clusters molecular signals within each molecular class, leveraging the shared spatial structure. A separately exchangeable framework is first considered, and then extended to handle spatial data via hidden Markov random fields. For scalability, we implement an efficient mean-field variational inference algorithm tailored for multi-dataset analysis. After validating the efficacy of our method on simulated scenarios, we demonstrate the applicability of our model in a real-world case study, where multiomics measurements were performed on kidney tissue affected by clear cell renal cell carcinoma. The nested, hierarchical structure of Poseidon, combined with its principled inferential framework, allows the extraction of interesting biological insights, such as clear tissue segmentation and biomarker detection.

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arXiv2025

Decoding Neuronal Ensembles from Spatially-Referenced Calcium Traces: A Bayesian Semiparametric Approach

Understanding how neurons coordinate their activity is a fundamental question in neuroscience, with implications for learning, memory, and neurological disorders. Calcium imaging has emerged as a powerful method to observe large-scale neuronal activity in freely moving animals, providing time-resolved recordings of hundreds of neurons. However, fluorescence signals are noisy and only indirectly reflect underlying spikes of neuronal activity, complicating the extraction of reliable patterns of neuronal coordination. We introduce a fully Bayesian, semiparametric model that jointly infers spiking activity and identifies functionally coherent neuronal ensembles from calcium traces. Our approach models each neuron's spiking probability through a latent Gaussian process and encourages anatomically coherent clustering using a location-dependent stick-breaking prior. A spike-and-slab Dirichlet process captures heterogeneity in spike amplitudes while filtering out negligible events. We consider calcium imaging data from the hippocampal CA1 region of a mouse as it navigates a circular arena, a setting critical for understanding spatial memory and neuronal representation of environments. Our model uncovers spatially structured co-activation patterns among neurons and can be employed to reveal how ensemble structures vary with the animal's position.

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arXiv2025

sanba: An R Package for Bayesian Clustering of Distributions via Shared Atoms Nested Models

Nested data structures arise when observations are grouped into distinct units, such as patients within hospitals or students within schools. Accounting for this hierarchical organization is essential for valid inference, as ignoring it can lead to biased estimates and poor generalization. This article addresses the challenge of clustering both individual observations and their corresponding groups while flexibly estimating group-specific densities. Bayesian nested mixture models offer a principled and robust framework for this task. However, their practical use has often been limited by computational complexity. To overcome this barrier, we present sanba, an R package for Bayesian analysis of grouped data using nested mixture models with a shared set of atoms, a structure recently introduced in the statistical literature. The package provides multiple inference strategies, including state-of-the-art Markov Chain Monte Carlo routines and variational inference algorithms tailored for large-scale datasets. All core functions are implemented in C++ and seamlessly integrated into R, making sanba a fast and user-friendly tool for fitting nested mixture models with modern Bayesian algorithms.

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arXiv2024

A finite-infinite shared atoms nested model for the Bayesian analysis of large grouped data

The use of hierarchical mixture priors with shared atoms has recently flourished in the Bayesian literature for partially exchangeable data. Leveraging on nested levels of mixtures, these models allow the estimation of a two-layered data partition: across groups and across observations. This paper discusses and compares the properties of such modeling strategies when the mixing weights are assigned either a finite-dimensional Dirichlet distribution or a Dirichlet process prior. Based on these considerations, we introduce a novel hierarchical nonparametric prior based on a finite set of shared atoms, a specification that enhances the flexibility of the induced random measures and the availability of fast posterior inference. To support these findings, we analytically derive the induced prior correlation structure and partially exchangeable partition probability function. Additionally, we develop a novel mean-field variational algorithm for posterior inference to boost the applicability of our nested model to large multivariate data. We then assess and compare the performance of the different shared-atom specifications via simulation. We also show that our variational proposal is highly scalable and that the accuracy of the posterior density estimate and the estimated partition is comparable with state-of-the-art Gibbs sampler algorithms. Finally, we apply our model to a real dataset of Spotify's song features, simultaneously segmenting artists and songs with similar characteristics.

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arXiv2023

Multiple hypothesis screening using mixtures of non-local distributions with applications to genomic studies

The analysis of large-scale datasets, especially in biomedical contexts, frequently involves a principled screening of multiple hypotheses. The celebrated two-group model jointly models the distribution of the test statistics with mixtures of two competing densities, the null and the alternative distributions. We investigate the use of weighted densities and, in particular, non-local densities as working alternative distributions, to enforce separation from the null and thus refine the screening procedure. We show how these weighted alternatives improve various operating characteristics, such as the Bayesian False Discovery rate, of the resulting tests for a fixed mixture proportion with respect to a local, unweighted likelihood approach. Parametric and nonparametric model specifications are proposed, along with efficient samplers for posterior inference. By means of a simulation study, we exhibit how our model compares with both well-established and state-of-the-art alternatives in terms of various operating characteristics. Finally, to illustrate the versatility of our method, we conduct three differential expression analyses with publicly-available datasets from genomic studies of heterogeneous nature.

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arXiv2023

intRinsic: an R Package for Model-Based Estimation of the Intrinsic Dimension of a Dataset

This article illustrates intRinsic, an R package that implements novel state-of-the-art likelihood-based estimators of the intrinsic dimension of a dataset, an essential quantity for most dimensionality reduction techniques. In order to make these novel estimators easily accessible, the package contains a small number of high-level functions that rely on a broader set of efficient, low-level routines. Generally speaking, intRinsic encompasses models that fall into two categories: homogeneous and heterogeneous intrinsic dimension estimators. The first category contains the two nearest neighbors estimator, a method derived from the distributional properties of the ratios of the distances between each data point and its first two closest neighbors. The functions dedicated to this method carry out inference under both the frequentist and Bayesian frameworks. In the second category, we find the heterogeneous intrinsic dimension algorithm, a Bayesian mixture model for which an efficient Gibbs sampler is implemented. After presenting the theoretical background, we demonstrate the performance of the models on simulated datasets. This way, we can facilitate the exposition by immediately assessing the validity of the results. Then, we employ the package to study the intrinsic dimension of the Alon dataset, obtained from a famous microarray experiment. Finally, we show how the estimation of homogeneous and heterogeneous intrinsic dimensions allows us to gain valuable insights into the topological structure of a dataset.

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arXiv2023

A Horseshoe mixture model for Bayesian screening with an application to light sheet fluorescence microscopy in brain imaging

In this paper, we focus on identifying differentially activated brain regions using a light sheet fluorescence microscopy - a recently developed technique for whole-brain imaging. Most existing statistical methods solve this problem by partitioning the brain regions into two classes: significantly and non-significantly activated. However, for the brain imaging problem at the center of our study, such binary grouping may provide overly simplistic discoveries by filtering out weak but important signals, that are typically adulterated by the noise present in the data. To overcome this limitation, we introduce a new Bayesian approach that allows classifying the brain regions into several tiers with varying degrees of relevance. Our approach is based on a combination of shrinkage priors - widely used in regression and multiple hypothesis testing problems - and mixture models - commonly used in model-based clustering. In contrast to the existing regularizing prior distributions, which use either the spike-and-slab prior or continuous scale mixtures, our class of priors is based on a discrete mixture of continuous scale mixtures and devises a cluster-shrinkage version of the Horseshoe prior. As a result, our approach provides a more general setting for Bayesian sparse estimation, drastically reduces the number of shrinkage parameters needed, and creates a framework for sharing information across units of interest. We show that this approach leads to more biologically meaningful and interpretable results in our brain imaging problem, since it allows the discrimination between active and inactive regions, while at the same time ranking the discoveries into clusters representing tiers of similar importance.

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arXiv2022

Variational Inference for Semiparametric Bayesian Novelty Detection in Large Datasets

After being trained on a fully-labeled training set, where the observations are grouped into a certain number of known classes, novelty detection methods aim to classify the instances of an unlabeled test set while allowing for the presence of previously unseen classes. These models are valuable in many areas, ranging from social network and food adulteration analyses to biology, where an evolving population may be present. In this paper, we focus on a two-stage Bayesian semiparametric novelty detector, also known as Brand, recently introduced in the literature. Leveraging on a model-based mixture representation, Brand allows clustering the test observations into known training terms or a single novelty term. Furthermore, the novelty term is modeled with a Dirichlet Process mixture model to flexibly capture any departure from the known patterns. Brand was originally estimated using MCMC schemes, which are prohibitively costly when applied to high-dimensional data. To scale up Brand applicability to large datasets, we propose to resort to a variational Bayes approach, providing an efficient algorithm for posterior approximation. We demonstrate a significant gain in efficiency and excellent classification performance with thorough simulation studies. Finally, to showcase its applicability, we perform a novelty detection analysis using the openly-available Statlog dataset, a large collection of satellite imaging spectra, to search for novel soil types.

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arXiv2022

On the intrinsic dimensionality of Covid-19 data: a global perspective

This paper aims to develop a global perspective of the complexity of the relationship between the standardised per-capita growth rate of Covid-19 cases, deaths, and the OxCGRT Covid-19 Stringency Index, a measure describing a country's stringency of lockdown policies. To achieve our goal, we use a heterogeneous intrinsic dimension estimator implemented as a Bayesian mixture model, called Hidalgo. We identify that the Covid-19 dataset may project onto two low-dimensional manifolds without significant information loss. The low dimensionality suggests strong dependency among the standardised growth rates of cases and deaths per capita and the OxCGRT Covid-19 Stringency Index for a country over 2020-2021. Given the low dimensional structure, it may be feasible to model observable Covid-19 dynamics with few parameters. Importantly, we identify spatial autocorrelation in the intrinsic dimension distribution worldwide. Moreover, we highlight that high-income countries are more likely to lie on low-dimensional manifolds, likely arising from aging populations, comorbidities, and increased per capita mortality burden from Covid-19. Finally, we temporally stratify the dataset to examine the intrinsic dimension at a more granular level throughout the Covid-19 pandemic.

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arXiv2021

A Two-Stage Bayesian Semiparametric Model for Novelty Detection with Robust Prior Information

Novelty detection methods aim at partitioning the test units into already observed and previously unseen patterns. However, two significant issues arise: there may be considerable interest in identifying specific structures within the novelty, and contamination in the known classes could completely blur the actual separation between manifest and new groups. Motivated by these problems, we propose a two-stage Bayesian semiparametric novelty detector, building upon prior information robustly extracted from a set of complete learning units. We devise a general-purpose multivariate methodology that we also extend to handle functional data objects. We provide insights on the model behavior by investigating the theoretical properties of the associated semiparametric prior. From the computational point of view, we propose a suitable $\boldsymbolξ$-sequence to construct an independent slice-efficient sampler that takes into account the difference between manifest and novelty components. We showcase our model performance through an extensive simulation study and applications on both multivariate and functional datasets, in which diverse and distinctive unknown patterns are discovered.

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arXiv2021

Distributional Results for Model-Based Intrinsic Dimension Estimators

Modern datasets are characterized by a large number of features that may conceal complex dependency structures. To deal with this type of data, dimensionality reduction techniques are essential. Numerous dimensionality reduction methods rely on the concept of intrinsic dimension, a measure of the complexity of the dataset. In this article, we first review the TWO-NN model, a likelihood-based intrinsic dimension estimator recently introduced in the literature. The TWO-NN estimator is based on the statistical properties of the ratio of the distances between a point and its first two nearest neighbors, assuming that the points are a realization from an homogeneous Poisson point process. We extend the TWO-NN theoretical framework by providing novel distributional results of consecutive and generic ratios of distances. These distributional results are then employed to derive intrinsic dimension estimators, called Cride and Gride. These novel estimators are more robust to noisy measurements than the TWO-NN and allow the study of the evolution of the intrinsic dimension as a function of the scale used to analyze the dataset. We discuss the properties of the different estimators with the help of simulation scenarios.

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arXiv2020

A Common Atom Model for the Bayesian Nonparametric Analysis of Nested Data

The use of high-dimensional data for targeted therapeutic interventions requires new ways to characterize the heterogeneity observed across subgroups of a specific population. In particular, models for partially exchangeable data are needed for inference on nested datasets, where the observations are assumed to be organized in different units and some sharing of information is required to learn distinctive features of the units. In this manuscript, we propose a nested Common Atoms Model (CAM) that is particularly suited for the analysis of nested datasets where the distributions of the units are expected to differ only over a small fraction of the observations sampled from each unit. The proposed CAM allows a two-layered clustering at the distributional and observational level and is amenable to scalable posterior inference through the use of a computationally efficient nested slice-sampler algorithm. We further discuss how to extend the proposed modeling framework to handle discrete measurements, and we conduct posterior inference on a real microbiome dataset from a diet swap study to investigate how the alterations in intestinal microbiota composition are associated with different eating habits. We further investigate the performance of our model in capturing true distributional structures in the population by means of a simulation study.

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arXiv2020

Data segmentation based on the local intrinsic dimension

One of the founding paradigms of machine learning is that a small number of variables is often sufficient to describe high-dimensional data. The minimum number of variables required is called the intrinsic dimension (ID) of the data. Contrary to common intuition, there are cases where the ID varies within the same data set. This fact has been highlighted in technical discussions, but seldom exploited to analyze large data sets and obtain insight into their structure. Here we develop a robust approach to discriminate regions with different local IDs and segment the points accordingly. Our approach is computationally efficient and can be proficiently used even on large data sets. We find that many real-world data sets contain regions with widely heterogeneous dimensions. These regions host points differing in core properties: folded vs unfolded configurations in a protein molecular dynamics trajectory, active vs non-active regions in brain imaging data, and firms with different financial risk in company balance sheets. A simple topological feature, the local ID, is thus sufficient to achieve an unsupervised segmentation of high-dimensional data, complementary to the one given by clustering algorithms.

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arXiv2020

The role of intrinsic dimension in high-resolution player tracking data -- Insights in basketball

A new range of statistical analysis has emerged in sports after the introduction of the high-resolution player tracking technology, specifically in basketball. However, this high dimensional data is often challenging for statistical inference and decision making. In this article, we employ Hidalgo, a state-of-the-art Bayesian mixture model that allows the estimation of heterogeneous intrinsic dimensions (ID) within a dataset and propose some theoretical enhancements. ID results can be interpreted as indicators of variability and complexity of basketball plays and games. This technique allows classification and clustering of NBA basketball player's movement and shot charts data. Analyzing movement data, Hidalgo identifies key stages of offensive actions such as creating space for passing, preparation/shooting and following through. We found that the ID value spikes reaching a peak between 4 and 8 seconds in the offensive part of the court after which it declines. In shot charts, we obtained groups of shots that produce substantially higher and lower successes. Overall, game-winners tend to have a larger intrinsic dimension which is an indication of more unpredictability and unique shot placements. Similarly, we found higher ID values in plays when the score margin is small compared to large margin ones. These outcomes could be exploited by coaches to obtain better offensive/defensive results.

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