Understanding When Poisson Log-Normal Models Outperform Penalized Poisson Regression for Microbiome Count Data
Authors: Daniel Agyapong, Julien Chiquet, Jane Marks, Toby Dylan Hocking
Organizations: School of Informatics, Computing, and Cyber Systems, Northern Arizona University, Flagstaff, Arizona, U.S.A. · UMR MIA Paris-Saclay, Université Paris-Saclay, AgroParisTech, INRAE, Palaiseau, France · Department of Biological Sciences, Northern Arizona University, Flagstaff, Arizona, U.S.A. · Département d’informatique, Université de Sherbrooke, Sherbrooke, Québec, Canada
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.
Figures & tables
Study (year)
Data / setting
Algorithms tested
Evaluation metrics
Kenney et al. (2021)
Simulations; microbiome example
Poisson PCA, PLN
Subspace recovery (principal angles); robustness to noise and exposure; runtime
Chiquet et al. (2021)
Multiple ecology/microbiome case studies
PLN, PLNPCA, PLNNetwork, PLNMixture
BIC/ICL for model order selection; illustrative fits across tasks
3-class accuracy for interaction type recovery; topology and size effects
Batardière et al. (2025)
High-zero simulations; cow microbiome
ZIPLN, PLN
In-sample log-likelihood (ELBO/BIC/AIC); latent dispersion; group discrimination
Table 1: Summary of prior benchmarks of PLN and Poisson algorithms.
Figure 1: Conceptual contrast between earlier evaluation practice and the count-prediction protocol used in this study. Previous work often assessed count models with in-sample fit criteria computed on the observed abundance matrix. Our benchmark instead withholds a target taxon, predicts its counts out of sample from the remaining taxa, and scores those predictions with held-out Poisson deviance under leave-one-taxon-out cross-validation.
Figure 2: Dataset-level winner as a function of N/D and MAC across the 20-dataset real-data benchmark. Blue circles: PLN achieves lower held-out Poisson deviance. Red squares: GLMNet(Poisson) achieves lower held-out Poisson deviance. The orange triangle marks American Gut 1, a GLMNet win at low N/D and high MAC that runs counter to the general pattern.
Figure 3: Representative datasets illustrating both directions of the PLN vs. GLMNet(Poisson) comparison. Top: datasets where PLN achieves lower held-out Poisson deviance. Bottom: datasets where GLMNet(Poisson) achieves lower held-out Poisson deviance. Each panel reports held-out Poisson deviance (mean ± SE across three outer cross-validation folds) for PLN, GLMNet(Poisson), and the featureless baseline. The annotated difference and p -value are from the paired comparison of PLN and GLMNet(Poisson) across folds.
Figure 4: Edge-recovery F1 score on five experimental ground-truth datasets for PLNNetwork and GLMNet(Poisson) . Datasets are grouped by ground-truth type: broad edge recovery (OMM12, OMM12 keystone 2023, PairInteraX) and local/directional (butyrate assembly 2021, host fitness 2018). Bars show mean F1 score over B=20 bootstrap resamples of the abundance matrix; error bars are ±1 SE.
Figure 5: Ground-truth and inferred networks for the OMM12 defined community (12 taxa). Each panel shows the experimental ground truth (left), the PLNNetwork prediction (centre), and the GLMNet(Poisson) prediction (right). Node labels are strain codes: KB1 ( E. faecalis ), YL2 ( B. animalis ), KB18 ( A. muris ), YL27 ( M. intestinale ), YL31 ( F. plautii ), YL32 ( E. clostridioformis ), YL44 ( A. muciniphila ), YL45 ( T. muris ), I46 ( C. innocuum ), I48 ( B. caecimuris ), I49 ( L. reuteri ), YL58 ( B. coccoides ). Edge colour indicates interaction sign (blue: positive, orange: negative).
Figure 6: Median wall time (left) and peak memory (right) as a function of the number of taxa D , profiled on the Vogtmann et al. stool species dataset ( N=110 ) using the atime R package. Each point is the median of three runs; D ranges from 10 to 1000. Both axes are on a log scale.
Generalized linear models connect predictors to non-Gaussian outcomes through a link function, supporting interpretable prediction and statistical inference.
Poisson non-negative matrix factorization (NMF) is a widely used method to find interpretable "parts-based" decompositions of count data. While many variants of Poisson NMF exist, existing methods assume that the "parts" in the decomposition combine additively. This assumption may be natural in some settings, but not in others. Here we introduce Poisson NMF with the shifted-log link function to relax this assumption. The shifted-log link function has a single tuning parameter, and as this parameter varies the model changes from assuming that parts combine additively (i.e., standard Poisson NMF) to assuming that parts combine more multiplicatively. We provide an algorithm to fit this model by maximum likelihood, and also an approximation that substantially reduces computation time for large, sparse datasets (computations scale with the number of non-zero entries in the data matrix). We illustrate these new methods on a variety of real datasets. Our examples show how the choice of link function in Poisson NMF can substantively impact the results, and how in some settings the use of a shifted-log link function may improve interpretability compared with the standard, additive link.
Eric Weine, Peter Carbonetto, Rafael A. Irizarry +1
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA · Department of Human Genetics, University of Chicago, Chicago, IL, USA · Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA +1
Physics-Informed Neural Network (PINN) is a way of including knowledge in the form of equations in Machine Learning methods. Beyond equations, knowledge exists in other forms, such as text and network structure. While existing PINN-based approaches discover equation parameters from data, they rely solely on experimental measurements. We propose a new PINN framework that enriches parameter discovery by incorporating auxiliary knowledge sources. We instantiate our framework for microbiology, where generalised Lotka-Volterra (gLV) serves as a biological foundation for modelling microbial communities. We demonstrate that incorporating knowledge improves microbial community modelling. Our framework enriches the gLV parameters using peer-reviewed metagenomics literature, as text provides biological context on external influences that gLV alone cannot capture. We combine this knowledge with experimental measurements of microbial abundance using a data-driven integration approach. We integrate network-based structural knowledge by explicitly modelling microbial interactions. Our knowledge-inclusive framework infers microbial networks, revealing ecological insights. We validate these findings against ecological roles documented in the literature. We evaluate on real and simulated datasets spanning human- and plant-associated microbial communities. Our framework improves over the state-of-the-art by up to 53%, even without knowledge. Knowledge addition yields gains of up to 23% in Bray-Curtis Dissimilarity-based accuracy and 47% in R2.
AI, Optimisation and Pattern Recognition Lab, Department of Mechanical Engineering, University of Melbourne, Melbourne, Victoria, Australia · Biodiversity Research Center, Academia Sinica, Taipei, Taiwan
Spike-and-slab regression is a standard Bayesian formulation of variable selection: it returns a posterior distribution over which candidate effects are active rather than a single selected subset, so that every candidate effect carries an inclusion probability. Its cost grows exponentially with the number of candidate effects, so the posterior can be enumerated exactly only when the number of predictors is small. Beyond that reach, the posterior has to be approximated, typically by Markov chain Monte Carlo over the model space, which requires a fresh run for every dataset and, within a fixed budget of steps, may fail to converge. We present LinearPFN, a prior-data fitted transformer network that amortizes spike-and-slab inference for linear models with main effects and pairwise interactions. The network is pretrained once on synthetic datasets, drawn from an explicitly specified prior, and a single forward pass over a new dataset returns posterior inclusion probabilities, posterior-mean coefficients and posterior predictive distributions with no per-dataset fitting. The prior is conjugate by design, so that the posterior for each fixed set of active effects has a closed form, and wherever the exact posterior is still computable by enumeration we verify the network's outputs against it. On real predictor matrices from published social-science datasets, with outcomes drawn from the prior so that the true active set is known, LinearPFN attains a higher per-dataset selection AUC and a higher F1 under the median probability model rule than five classical baselines. The lead holds when the coefficients, the interactions or the noise depart from the prior. Code: https://github.com/schiekiera/LinearPFN. Trained model: https://huggingface.co/schiekiera/LinearPFN.
Louis Schiekiera, Max Zimmer, Christophe Roux +3
Institute of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany · Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany · Department for AI in Society, Science, and Technology, Zuse Institute Berlin, Germany +1