arXiv subjects

Julien Chiquet

Publications and source records attributed to Julien Chiquet.

At least 19 recordsLinked to original sources

arXiv2026

Data Shared Neighbourhood Selection for multi-condition network inference

External stresses may affect both the circulating levels of specific biomarkers and disturb the correlation structures across molecular entities. The contribution of both types of dysregulations to the subsequent risk of disease are yet to be evaluated. We propose Data Shared Neighbourhood Selection (DSNS), a joint network inference method for estimating preserved and altered conditional association structures across related conditions. DSNS combines neighbourhood selection with the Data Shared Lasso decomposition, representing each nodewise regression coefficient as the sum of a shared component and a sparse condition-specific deviation. This provides an interpretable decomposition of molecular associations while retaining the computational advantages of neighbourhood selection. We also adapt the Stability Approach to Regularisation Selection (StARS) to this two-parameter joint estimation setting. In simulations involving sparse, hub-based and rewiring perturbation mechanisms, DSNS matched the best joint estimation methods for two conditions and outperformed them as the number of conditions increased, while remaining substantially faster than graphical lasso frameworks. Applied to prediagnostic inflammatory proteomic data from future lung cancer cases and matched controls in the EPIC-Italy and NOWAC cohorts, DSNS highlighted altered associations involving CDCP1 and IL10, two established lung cancer risk markers, as well as differential associations involving proteins not selected by risk models.

stat.AP↗

arXiv2026

Understanding When Poisson Log-Normal Models Outperform Penalized Poisson Regression for Microbiome Count Data

Multivariate count models are often justified by their ability to capture latent dependence, but researchers receive little guidance on when this added structure improves on simpler penalized marginal Poisson regression. We study this question using real microbiome data under a unified held-out evaluation framework. For count prediction, we compare PLN and GLMNet(Poisson) on 20 datasets spanning 32 to 18,270 samples and 24 to 257 taxa, using held-out Poisson deviance under leave-one-taxon-out prediction with 3-fold sample cross-validation rather than synthetic or in-sample criteria. For network inference, we compare PLNNetwork and GLMNet(Poisson) neighborhood selection on five publicly available datasets with experimentally validated microbial interaction truth. PLN outperforms GLMNet(Poisson) on most count-prediction datasets, with gains up to 38 percent. The primary predictor of the winner is the sample-to-taxon ratio, with mean absolute correlation as the strongest secondary signal and overdispersion as an additional predictor. PLNNetwork performs best on broad undirected interaction benchmarks, whereas GLMNet(Poisson) is better aligned with local or directional effects. Taken together, these results provide guidance for choosing between latent multivariate count models and penalized Poisson regression in biological count prediction and interaction recovery.

cs.LG↗

arXiv2026

Overcoming Barriers to Computational Reproducibility

Computational reproducibility, the possibility for independent researchers to exactly reproduce published empirical results, is fundamental to science. Despite its importance, the proportion of research articles aiming for reproducibility remains low and uneven across disciplines. Barriers include a perceived lack of incentives for researchers and journals, practical challenges in preparing reproducible materials, and the absence of harmonised standards of reproducibility processes and requirements by journals. Existing guidance is often highly technical, reaching mainly those already engaged with reproducible research. In this paper, we first synthesize evidence on the benefits of reproducibility for both authors and journals. Drawing on our extensive experience in reproducibility checking at various journals, we then put forward concise, pragmatic guidelines for creating reproducible analyses across disciplines. We further review current reproducibility policies of selected journals, illustrating the substantial heterogeneity in requirements and procedures. Motivated by the latter, we propose conceptual foundations for a harmonised multi-tier system of reproducibility standards that could support transparent, consistent assessment across journals and research communities. Our goal as journal (reproducibility) editors and contributors to the MaRDI initiative is to encourage broader adoption of reproducibility practices, in particular by lowering practical barriers for authors and journals.

cs.DL↗

arXiv2025

Deep Generative Models for Discrete Genotype Simulation

Deep generative models open new avenues for simulating realistic genomic data while preserving privacy and addressing data accessibility constraints. While previous studies have primarily focused on generating gene expression or haplotype data, this study explores generating genotype data in both unconditioned and phenotype-conditioned settings, which is inherently more challenging due to the discrete nature of genotype data. In this work, we developed and evaluated commonly used generative models, including Variational Autoencoders (VAEs), Diffusion Models, and Generative Adversarial Networks (GANs), and proposed adaptation tailored to discrete genotype data. We conducted extensive experiments on large-scale datasets, including all chromosomes from cow and multiple chromosomes from human. Model performance was assessed using a well-established set of metrics drawn from both deep learning and quantitative genetics literature. Our results show that these models can effectively capture genetic patterns and preserve genotype-phenotype association. Our findings provide a comprehensive comparison of these models and offer practical guidelines for future research in genotype simulation. We have made our code publicly available at https://github.com/SihanXXX/DiscreteGenoGen.

q-bio.GN↗

arXiv2025

An integrated method for clustering and association network inference

High dimensional Gaussian graphical models provide a rigorous framework to describe a network of statistical dependencies between entities, such as genes in genomic regulation studies or species in ecology. Penalized methods, including the standard Graphical-Lasso, are well-known approaches to infer the parameters of these models. As the number of variables in the model (of entities in the network) grow, the network inference and interpretation become more complex. The Normal-Block model is introduced, a new model that clusters variables and consider a network at the cluster level. Normal-Block both adds structure to the network and reduces its size. The approach builds on Graphical-Lasso to add a penalty on the network's edges and limit the detection of spurious dependencies. A zero-inflated version of the model is also proposed to account for real-world data properties. For the inference procedure, two approaches are introduced, a straightforward method based on state-of-the-art approaches and an original, more rigorous method that simultaneously infers the clustering of variables and the association network between clusters, using a penalized variational Expectation-Maximization approach. An implementation of the model in R, in a package called \textbf{normalblockr}, is available on github\footnote{https://github.com/jeannetous/normalblockr}. The results of the models in terms of clustering and network inference are presented, using both simulated data and various types of real-world data (proteomics and words occurrences on webpages).

stat.ME↗

arXiv2024

Evaluating Parameter Uncertainty in the Poisson Lognormal Model with Corrected Variational Estimators

Count data analysis is essential across diverse fields, from ecology and accident analysis to single-cell RNA sequencing (scRNA-seq) and metagenomics. While log transformations are computationally efficient, model-based approaches such as the Poisson-Log-Normal (PLN) model provide robust statistical foundations and are more amenable to extensions. The PLN model, with its latent Gaussian structure, not only captures overdispersion but also enables correlation between variables and inclusion of covariates, making it suitable for multivariate count data analysis. Variational approximations are a golden standard to estimate parameters of complex latent variable models such as PLN, maximizing a surrogate likelihood. However, variational estimators lack theoretical statistical properties such as consistency and asymptotic normality. In this paper, we investigate the consistency and variance estimation of PLN parameters using M-estimation theory. We derive the Sandwich estimator, previously studied in Westling and McCormick (2019), specifically for the PLN model. We compare this approach to the variational Fisher Information method, demonstrating the Sandwich estimator's effectiveness in terms of coverage through simulation studies. Finally, we validate our method on a scRNA-seq dataset.

stat.ME↗

arXiv2024

Importance sampling-based gradient method for dimension reduction in Poisson log-normal model

High-dimensional count data poses significant challenges for statistical analysis, necessitating effective methods that also preserve explainability. We focus on a low rank constrained variant of the Poisson log-normal model, which relates the observed data to a latent low-dimensional multivariate Gaussian variable via a Poisson distribution. Variational inference methods have become a golden standard solution to infer such a model. While computationally efficient, they usually lack theoretical statistical properties with respect to the model. To address this issue we propose a projected stochastic gradient scheme that directly maximizes the log-likelihood. We prove the convergence of the proposed method when using importance sampling for estimating the gradient. Specifically, we obtain a rate of convergence of $O(T^{-1/2} + N^{-1})$ with $T$ the number of iterations and $N$ the number of Monte Carlo draws. The latter follows from a novel descent lemma for non convex $L$-smooth objective functions, and random biased gradient estimate. We also demonstrate numerically the efficiency of our solution compared to its variational competitor. Our method not only scales with respect to the number of observed samples but also provides access to the desirable properties of the maximum likelihood estimator.

math.OC↗

arXiv2024

Zero-inflation in the Multivariate Poisson Lognormal Family

Analyzing high-dimensional count data is a challenge and statistical model-based approaches provide an adequate and efficient framework that preserves explainability. The (multivariate) Poisson-Log-Normal (PLN) model is one such model: it assumes count data are driven by an underlying structured latent Gaussian variable, so that the dependencies between counts solely stems from the latent dependencies. However PLN doesn't account for zero-inflation, a feature frequently observed in real-world datasets. Here we introduce the Zero-Inflated PLN (ZIPLN) model, adding a multivariate zero-inflated component to the model, as an additional Bernoulli latent variable. The Zero-Inflation can be fixed, site-specific, feature-specific or depends on covariates. We estimate model parameters using variational inference that scales up to datasets with a few thousands variables and compare two approximations: (i) independent Gaussian and Bernoulli variational distributions or (ii) Gaussian variational distribution conditioned on the Bernoulli one. The method is assessed on synthetic data and the efficiency of ZIPLN is established even when zero-inflation concerns up to 90% of the observed counts. We then apply both ZIPLN and PLN to a cow microbiome dataset, containing 90.6% of zeroes. Accounting for zero-inflation significantly increases log-likelihood and reduces dispersion in the latent space, thus leading to improved group discrimination.

stat.ME↗

arXiv2023

A Probabilistic Graph Coupling View of Dimension Reduction

Most popular dimension reduction (DR) methods like t-SNE and UMAP are based on minimizing a cost between input and latent pairwise similarities. Though widely used, these approaches lack clear probabilistic foundations to enable a full understanding of their properties and limitations. To that extent, we introduce a unifying statistical framework based on the coupling of hidden graphs using cross entropy. These graphs induce a Markov random field dependency structure among the observations in both input and latent spaces. We show that existing pairwise similarity DR methods can be retrieved from our framework with particular choices of priors for the graphs. Moreover this reveals that these methods suffer from a statistical deficiency that explains poor performances in conserving coarse-grain dependencies. Our model is leveraged and extended to address this issue while new links are drawn with Laplacian eigenmaps and PCA.

math.PR↗

arXiv2023

Automated calibration of consensus weighted distance-based clustering approaches using sharp

In consensus clustering, a clustering algorithm is used in combination with a subsampling procedure to detect stable clusters. Previous studies on both simulated and real data suggest that consensus clustering outperforms native algorithms. We extend here consensus clustering to allow for attribute weighting in the calculation of pairwise distances using existing regularised approaches. We propose a procedure for the calibration of the number of clusters (and regularisation parameter) by maximising a novel consensus score calculated directly from consensus clustering outputs, making it extremely computationally competitive. Our simulation study shows better clustering performances of (i) models calibrated by maximising our consensus score compared to existing calibration scores, and (ii) weighted compared to unweighted approaches in the presence of features that do not contribute to cluster definition. Application on real gene expression data measured in lung tissue reveals clear clusters corresponding to different lung cancer subtypes. The R package sharp (version 1.4.0) is available on CRAN.

stat.ME↗

arXiv2023

Automated calibration for stability selection in penalised regression and graphical models

Stability selection represents an attractive approach to identify sparse sets of features jointly associated with an outcome in high-dimensional contexts. We introduce an automated calibration procedure via maximisation of an in-house stability score and accommodating a priori-known block structure (e.g. multi-OMIC) data. It applies to (LASSO) penalised regression and graphical models. Simulations show our approach outperforms non-stability-based and stability selection approaches using the original calibration. Application of multi-block graphical LASSO on real (epigenetic and transcriptomic) data from the Norwegian Women and Cancer study reveals a central/credible and novel cross-OMIC role of LRRN3 in the biological response to smoking. Proposed approaches were implemented in the R package sharp.

stat.ME↗

arXiv2021

missSBM: An R Package for Handling Missing Values in the Stochastic Block Model

The Stochastic Block Model (SBM) is a popular probabilistic model for random graphs. It is commonly used for clustering network data by aggregating nodes that share similar connectivity patterns into blocks. When fitting an SBM to a network which is partially observed, it is important to take into account the underlying process that generates the missing values, otherwise the inference may be biased. This paper introduces missSBM, an R-package fitting the SBM when the network is partially observed, i.e., the adjacency matrix contains not only 1's or 0's encoding presence or absence of edges but also NA's encoding missing information between pairs of nodes. This package implements a set of algorithms for fitting the binary SBM, possibly in the presence of external covariates, by performing variational inference adapted to several observation processes. Our implementation automatically explores different block numbers to select the most relevant model according to the Integrated Classification Likelihood (ICL) criterion. The ICL criterion can also help determine which observation process better corresponds to a given dataset. Finally, missSBM can be used to perform imputation of missing entries in the adjacency matrix. We illustrate the package on a network data set consisting of interactions between political blogs sampled during the French presidential election in 2007.

stat.CO↗

arXiv2020

Adjusting the adjusted Rand Index -- A multinomial story

The Adjusted Rand Index ($ARI$) is arguably one of the most popular measures for cluster comparison. The adjustment of the $ARI$ is based on a hypergeometric distribution assumption which is unsatisfying from a modeling perspective as (i) it is not appropriate when the two clusterings are dependent, (ii) it forces the size of the clusters, and (iii) it ignores randomness of the sampling. In this work, we present a new "modified" version of the Rand Index. First, we redefine the $MRI$ by only counting the pairs consistent by similarity and ignoring the pairs consistent by difference, increasing the interpretability of the score. Second, we base the adjusted version, $MARI$, on a multinomial distribution instead of a hypergeometric distribution. The multinomial model is advantageous as it does not force the size of the clusters, properly models randomness, and is easily extended to the dependant case. We show that the $ARI$ is biased under the multinomial model and that the difference between the $ARI$ and $MARI$ can be large for small $n$ but essentially vanish for large $n$, where $n$ is the number of individuals. Finally, we provide an efficient algorithm to compute all these quantities ($(A)RI$ and $M(A)RI$) by relying on a sparse representation of the contingency table in our \texttt{aricode} package. The space and time complexity is linear in the number of samples and importantly does not depend on the number of clusters as we do not explicitly compute the contingency table.

stat.ME↗

arXiv2020

Fast Computation of Genome-Metagenome Interaction Effects

Motivation. Association studies have been widely used to search for associations between common genetic variants observations and a given phenotype. However, it is now generally accepted that genes and environment must be examined jointly when estimating phenotypic variance. In this work we consider two types of biological markers: genotypic markers, which characterize an observation in terms of inherited genetic information, and metagenomic marker which are related to the environment. Both types of markers are available in their millions and can be used to characterize any observation uniquely. Objective. Our focus is on detecting interactions between groups of genetic and metagenomic markers in order to gain a better understanding of the complex relationship between environment and genome in the expression of a given phenotype. Contributions. We propose a novel approach for efficiently detecting interactions between complementary datasets in a high-dimensional setting with a reduced computational cost. The method, named SICOMORE, reduces the dimension of the search space by selecting a subset of supervariables in the two complementary datasets. These supervariables are given by a weighted group structure defined on sets of variables at different scales. A Lasso selection is then applied on each type of supervariable to obtain a subset of potential interactions that will be explored via linear model testing. Results. We compare SICOMORE with other approaches in simulations, with varying sample sizes, noise, and numbers of true interactions. SICOMORE exhibits convincing results in terms of recall, as well as competitive performances with respect to running time. The method is also used to detect interaction between genomic markers in Medicago truncatula and metagenomic markers in its rhizosphere bacterial community. Software availability. A R package is available, along with its documentation and associated scripts, allowing the reader to reproduce the results presented in the paper.

stat.AP↗

arXiv2020

Identification of deregulated transcription factors involved in subtypes of cancers

We propose a methodology for the identification of transcription factors involved in the deregulation of genes in tumoral cells. This strategy is based on the inference of a reference gene regulatory network that connects transcription factors to their downstream targets using gene expression data. The behavior of genes in tumor samples is then carefully compared to this network of reference to detect deregulated target genes. A linear model is finally used to measure the ability of each transcription factor to explain those deregulations. We assess the performance of our method by numerical experiments on a breast cancer data set. We show that the information about deregulation is complementary to the expression data as the combination of the two improves the supervised classification performance of samples into cancer subtypes.

q-bio.MN↗

arXiv2019

Variational Inference for Stochastic Block Models from Sampled Data

This paper deals with non-observed dyads during the sampling of a network and consecutive issues in the inference of the Stochastic Block Model (SBM). We review sampling designs and recover Missing At Random (MAR) and Not Missing At Random (NMAR) conditions for the SBM. We introduce variants of the variational EM algorithm for inferring the SBM under various sampling designs (MAR and NMAR) all available as an R package. Model selection criteria based on Integrated Classification Likelihood are derived for selecting both the number of blocks and the sampling design. We investigate the accuracy and the range of applicability of these algorithms with simulations. We explore two real-world networks from ethnology (seed circulation network) and biology (protein-protein interaction network), where the interpretations considerably depends on the sampling designs considered.

stat.ME↗

arXiv2018

Variational inference for sparse network reconstruction from count data

In multivariate statistics, the question of finding direct interactions can be formulated as a problem of network inference - or network reconstruction - for which the Gaussian graphical model (GGM) provides a canonical framework. Unfortunately, the Gaussian assumption does not apply to count data which are encountered in domains such as genomics, social sciences or ecology. To circumvent this limitation, state-of-the-art approaches use two-step strategies that first transform counts to pseudo Gaussian observations and then apply a (partial) correlation-based approach from the abundant literature of GGM inference. We adopt a different stance by relying on a latent model where we directly model counts by means of Poisson distributions that are conditional to latent (hidden) Gaussian correlated variables. In this multivariate Poisson lognormal-model, the dependency structure is completely captured by the latent layer. This parametric model enables to account for the effects of covariates on the counts. To perform network inference, we add a sparsity inducing constraint on the inverse covariance matrix of the latent Gaussian vector. Unlike the usual Gaussian setting, the penalized likelihood is generally not tractable, and we resort instead to a variational approach for approximate likelihood maximization. The corresponding optimization problem is solved by alternating a gradient ascent on the variational parameters and a graphical-Lasso step on the covariance matrix. We show that our approach is highly competitive with the existing methods on simulation inspired from microbiological data. We then illustrate on three various data sets how accounting for sampling efforts via offsets and integrating external covariates (which is mostly never done in the existing literature) drastically changes the topology of the inferred network.

stat.ME↗

arXiv2018

Variational inference for probabilistic Poisson PCA

Many application domains such as ecology or genomics have to deal with multivariate non Gaussian observations. A typical example is the joint observation of the respective abundances of a set of species in a series of sites, aiming to understand the co-variations between these species. The Gaussian setting provides a canonical way to model such dependencies, but does not apply in general. We consider here the multivariate exponential family framework for which we introduce a generic model with multivariate Gaussian latent variables. We show that approximate maximum likelihood inference can be achieved via a variational algorithm for which gradient descent easily applies. We show that this setting enables us to account for covariates and offsets. We then focus on the case of the Poisson-lognormal model in the context of community ecology. We demonstrate the efficiency of our algorithm on microbial ecology datasets. We illustrate the importance of accounting for the effects of covariates to better understand interactions between species.

stat.ME↗