Guy Wolf

Biography

Guy Wolf is a Full Professor in the Department of Mathematics and Statistics (DMS) at the Université de Montréal (UdeM), a Canada CIFAR AI Chair & Core Academic Member at Mila (the Quebec AI institute), an Associate Researcher with CRCHUM (the Montreal university hospital research center), and a participating PI in the Helmholtz International Lab for Causal Cell Dynamics.

In 2024 he has been awarded a Humboldt Experienced Research Fellowship, as part of which he was a visiting professor at Heidelberg University (2024) and Helmholtz Munich (2024-2026) in Germany. Prior to joining UdeM and Mila, he was a Gibbs Assistant Professor (2015-2018) in the Applied Math Program and an Associate Research Scientist in the Department of Genetics (2018) at Yale University (CT, USA). Previously, he was a Postdoctoral Researcher (2013-2015) in the Department of Computer Science at École Normale Supérieure in Paris (France). He holds a Ph.D. in Computer Science from Tel Aviv University (Israel), and has five years of prior experience in IT software design & development for data analysis in military settings.

His current research focuses on guided representation learning for data exploration, including methods that leverage manifold learning and geometric deep learning for dimensionality reduction, visualization, denoising, data augmentation, and coarse graining. While relevant for a wide range of applications, he is particularly interested in the intersection of AI & health, including tools supporting exploratory analysis of biomedical data, e.g., in single-cell multiomics, drug discovery, and neuroscience.

Current Students

Adrien Aumon

PhD - Université de Montréal

adrien.aumon@mila.quebec

Semih Cantürk

PhD - Université de Montréal

semihcanturk00@gmail.com

Joao Felipe Carneiro Barbosa Rocha

Collaborating researcher - Yale University

joaofelipe.rocha@mila.quebec

sebastian.damrich@mila.quebec

Sebastian Damrich

Collaborating researcher - University of Tübingen

Maxine Dussault

Master's Research - Université de Montréal

Co-supervisor :

Margarida Carvalho

maxine.dussault@mila.quebec

Stefan Horoi

PhD - Université de Montréal

stefan.horoi@mila.quebec

Master's Research - Concordia University

Principal supervisor :

xiaolong.huang@mila.quebec

Collaborating Alumni - Université de Montréal

guillaume.huguet@mila.quebec

Paul Janson

PhD - Concordia University

Principal supervisor :

myriam.lizotte@mila.quebec

paul.janson@mila.quebec

PhD - Université de Montréal

Gabriele Malagoli

Independent visiting researcher - Helmholtz Munich

gabriele.malagoli@mila.quebec

Philippe Martin

PhD - Université de Montréal

Co-supervisor :

Paul François

philippe.martin@mila.quebec

Paria Mehrbod

Master's Research - Concordia University

Principal supervisor :

paria.mehrbod@mila.quebec

Lydia Mezrag

PhD - Université de Montréal

lydia.mezrag@mila.quebec

Kevin Moon

Collaborating researcher

Sacha Morin

PhD - Université de Montréal

Co-supervisor :

Liam Paull

sacha.morin@mila.quebec

Postdoctorate - Concordia University

Principal supervisor :

geraldin.nanfack@mila.quebec

Shuang Ni

PhD - Université de Montréal

shuang.ni@mila.quebec

Albert Orozco Camacho

PhD - Concordia University

Principal supervisor :

Jake Rhodes

Collaborating researcher - BYU

rhodes@stat.byu.edu

thomas.sabourin@mila.quebec

Thomas Sabourin

PhD - Université de Montréal

johannes.schmidt@mila.quebec

Johannes Schmidt

Independent visiting researcher - University of Fribourg

PhD - Université de Montréal

Principal supervisor :

Julie Hussin

matthew.scicluna@mila.quebec

Ammar Sherif

PhD - Concordia University

Principal supervisor :

francisco.jose.tellez@mila.quebec

ammar.sherif@mila.quebec

Simeon Tchoffo

PhD - Université de Montréal

simeontchoffo@gmail.com

Francisco Tellez

Master's Research - Université de Montréal

Jesuino Vieira Filho

Master's Research - Université de Montréal

Collaborating Alumni - Université de Montréal

Co-supervisor :

yanlei.zhang@mila.quebec

Exploring the COVID-19 Interferon Paradox with Dimensionality Reduction and Clustering

Blog Posts

Graph and representation of working methodology, and graph of data on deaths 60 days after onset of symptoms.

February 19, 2025

Sacha Morin

Elsa Brunet-Ratnasingham

Guy Wolf

Read the article

Publications

Noisy Data Visualization using Functional Data Analysis

Haozhe Chen

Andres Felipe Duque Correa

Kevin R. Moon

Data visualization via dimensionality reduction is an important tool in exploratory data analysis. However, when the data are noisy, many ex… (see more)isting methods fail to capture the underlying structure of the data. The method called Empirical Intrinsic Geometry (EIG) was previously proposed for performing dimensionality reduction on high dimensional dynamical processes while theoretically eliminating all noise. However, implementing EIG in practice requires the construction of high-dimensional histograms, which suffer from the curse of dimensionality. Here we propose a new data visualization method called Functional Information Geometry (FIG) for dynamical processes that adapts the EIG framework while using approaches from functional data analysis to mitigate the curse of dimensionality. We experimentally demonstrate that the resulting method outperforms a variant of EIG designed for visualization in terms of capturing the true structure, hyperparameter robustness, and computational speed. We then use our method to visualize EEG brain measurements of sleep activity.

2024-06-04

ArXiv (preprint)

arxiv.org

Supervised latent factor modeling isolates cell-type-specific transcriptomic modules that underlie Alzheimer’s disease progression

Liam Hodgson

Yue Li

Yasser Iturria-Medina

Jo Anne Stratton

Smita Krishnaswamy

David A. Bennett

Danilo Bzdok

Late onset Alzheimer’s disease (AD) is a progressive neurodegenerative disease, with brain changes beginning years before symptoms surface… (see more). AD is characterized by neuronal loss, the classic feature of the disease that underlies brain atrophy. However, GWAS reports and recent single-nucleus RNA sequencing (snRNA-seq) efforts have highlighted that glial cells, particularly microglia, claim a central role in AD pathophysiology. Here, we tailor pattern-learning algorithms to explore distinct gene programs by integrating the entire transcriptome, yielding distributed AD-predictive modules within the brain’s major cell-types. We show that these learned modules are biologically meaningful through the identification of new and relevant enriched signaling cascades. The predictive nature of our modules, especially in microglia, allows us to infer each subject’s progression along a disease pseudo-trajectory, confirmed by post-mortem pathological brain tissue markers. Additionally, we quantify the interplay between pairs of cell-type modules in the AD brain, and localized known AD risk genes to enriched module gene programs. Our collective findings advocate for a transition from cell-type-specificity to gene modules specificity to unlock the potential of unique gene programs, recasting the roles of recently reported genome-wide AD risk loci. Designing a supervised latent factor framework for snRNA-seq human brain, the authors find distinct Alzheimer’s-predictive gene modules across celltypes, suggesting subcelltype disease progression trajectories.

2024-05-16

Communications Biology (published)

Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity

Elsa Brunet-Ratnasingham

Sacha Morin

Haley E. Randolph

Marjorie Labrecque

Justin Bélair

Raphaël Lima-Barbosa

Amélie Pagliuzza

Lorie Marchitto

Michael Hultström

Julia Niessl

Rose Cloutier

Alina M. Sreng Flores

Nathalie Brassard

Mehdi Benlarbi

Jérémie Prévost

Shilei Ding

Sai Priya Anand

Gérémy Sannier

Eric Bareke

Hugo Zeberg … (see 24 more)

Miklos Lipcsey

Robert Frithiof

Anders Larsson

Sirui Zhou

Tomoko Nakanishi

David Morrison

Dani Vezina

Catherine Bourassa

Gabrielle Gendron-Lepage

Halima Medjahed

Floriane Point

Jonathan Richard

Catherine Larochelle

Alexandre Prat

Nathalie Arbour

Madeleine Durand

J Brent Richards

Kevin Moon

Nicolas Chomont

Andrés Finzi

Martine Tétreault

Luis Barreiro

Daniel E. Kaufmann

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological… (see more) patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.

2024-05-15

Nature Communications (published)

Towards Foundational Models for Molecular Learning on Large-Scale Multi-Task Datasets

Dominique Beaini

Shenyang Huang

Joao Alex Cunha

Zhiyi Li

Gabriela Moisescu-Pareja

Oleksandr Dymov

Samuel Maddrell-Mander

Callum McLean

Jama Hussein Mohamud

Michael Craig

Cristian Gabellini

Kerstin Klaser

Josef Dean

Cas Wognum … (see 14 more)

Maciej Sypetkowski

Hadrien Mary

Therence Bois

Andrew Fitzgibbon

Błażej Banaszewski

Chad Martin

Dominic Masters

Recently, pre-trained foundation models have shown significant advancements in multiple fields. However, the lack of datasets with labeled f… (see more)eatures and codebases has hindered the development of a supervised foundation model for molecular tasks. Here, we have carefully curated seven datasets specifically tailored for node- and graph-level prediction tasks to facilitate supervised learning on molecules. Moreover, to support the development of multi-task learning on our proposed datasets, we created the Graphium graph machine learning library. Our dataset collection encompasses two distinct categories. Firstly, the TOYMIX category modifies three small existing datasets with additional data for multi-task learning. Secondly, the LARGEMIX category includes four large-scale datasets with 344M graph-level data points and 409M node-level data points from ∼5M unique molecules. Finally, the ultra-large dataset contains 2,210M graph-level data points and 2,031M node-level data points coming from 86M molecules. Hence our datasets represent an order of magnitude increase in data volume compared to other 2D-GNN datasets. In addition, recognizing that molecule-related tasks often span multiple levels, we have designed our library to explicitly support multi-tasking, offering a diverse range of multi-level representations, i.e., representations at the graph, node, edge, and node-pair level. We equipped the library with an extensive collection of models and features to cover different levels of molecule analysis. By combining our curated datasets with this versatile library, we aim to accelerate the development of molecule foundation models. Datasets and code are available at https://github.com/datamol-io/graphium.

2024-05-06

International Conference on Learning Representations (Accept (poster))

Simulation-Free Schrödinger Bridges via Score and Flow Matching

Nikolay Malkin

Yanlei Zhang

We present simulation-free score and flow matching ([SF]…

2024-05-01

International Conference on Artificial Intelligence and Statistics (Accept (Poster))

proceedings.mlr.press

Harmony in Diversity: Merging Neural Networks with Canonical Correlation Analysis

Stefan Horoi

Albert Manuel Orozco Camacho

Combining the predictions of multiple trained models through ensembling is generally a good way to improve accuracy by leveraging the differ… (see more)ent learned features of the models, however it comes with high computational and storage costs. Model fusion, the act of merging multiple models into one by combining their parameters reduces these costs but doesn't work as well in practice. Indeed, neural network loss landscapes are high-dimensional and non-convex and the minima found through learning are typically separated by high loss barriers. Numerous recent works have been focused on finding permutations matching one network features to the features of a second one, lowering the loss barrier on the linear path between them in parameter space. However, permutations are restrictive since they assume a one-to-one mapping between the different models' neurons exists. We propose a new model merging algorithm, CCA Merge, which is based on Canonical Correlation Analysis and aims to maximize the correlations between linear combinations of the model features. We show that our alignment method leads to better performances than past methods when averaging models trained on the same, or differing data splits. We also extend this analysis into the harder setting where more than 2 models are merged, and we find that CCA Merge works significantly better than past methods. Our code is publicly available at https://github.com/shoroi/align-n-merge

2024-04-30

International Conference on Machine Learning (poster)

proceedings.mlr.press

Inferring dynamic regulatory interaction graphs from time series data with perturbations

Dhananjay Bhaskar

Sumner Magruder

Edward De Brouwer

Matheo Morales

Aarthi Venkat

Frederik Wenkel

Smita Krishnaswamy

Complex systems are characterized by intricate interactions between entities that evolve dynamically over time. Accurate inference of these … (see more)dynamic relationships is crucial for understanding and predicting system behavior. In this paper, we propose Regulatory Temporal Interaction Network Inference (RiTINI) for inferring time-varying interaction graphs in complex systems using a novel combination of space-and-time graph attentions and graph neural ordinary differential equations (ODEs). RiTINI leverages time-lapse signals on a graph prior, as well as perturbations of signals at various nodes in order to effectively capture the dynamics of the underlying system. This approach is distinct from traditional causal inference networks, which are limited to inferring acyclic and static graphs. In contrast, RiTINI can infer cyclic, directed, and time-varying graphs, providing a more comprehensive and accurate representation of complex systems. The graph attention mechanism in RiTINI allows the model to adaptively focus on the most relevant interactions in time and space, while the graph neural ODEs enable continuous-time modeling of the system's dynamics. We evaluate RiTINI's performance on various simulated and real-world datasets, demonstrating its state-of-the-art capability in inferring interaction graphs compared to previous methods.

2024-04-16

Proceedings of the Second Learning on Graphs Conference (published)

proceedings.mlr.press

Assessing Neural Network Representations During Training Using Noise-Resilient Diffusion Spectral Entropy

Danqi Liao

Chen Liu

Benjamin W Christensen

Alexander Tong

Guillaume Huguet

Maximilian Nickel

Ian Adelstein

Smita Krishnaswamy

Entropy and mutual information in neural networks provide rich information on the learning process, but they have proven difficult to comput… (see more)e reliably in high dimensions. Indeed, in noisy and high-dimensional data, traditional estimates in ambient dimensions approach a fixed entropy and are prohibitively hard to compute. To address these issues, we leverage data geometry to access the underlying manifold and reliably compute these information-theoretic measures. Specifically, we define diffusion spectral entropy (DSE) in neural representations of a dataset as well as diffusion spectral mutual information (DSMI) between different variables representing data. First, we show that they form noise-resistant measures of intrinsic dimensionality and relationship strength in high-dimensional simulated data that outperform classic Shannon entropy, nonparametric estimation, and mutual information neural estimation (MINE). We then study the evolution of representations in classification networks with supervised learning, self-supervision, or overfitting. We observe that (1) DSE of neural representations increases during training; (2) DSMI with the class label increases during generalizable learning but stays stagnant during overfitting; (3) DSMI with the input signal shows differing trends: on MNIST it increases, while on CIFAR-10 and STL-10 it decreases. Finally, we show that DSE can be used to guide better network initialization and that DSMI can be used to predict downstream classification accuracy across 962 models on ImageNet.

2024-03-12

Conference on Information Sciences and Systems (published)

Improving and Generalizing Flow-Based Generative Models with Minibatch Optimal Transport

Nikolay Malkin

Yanlei Zhang

Continuous normalizing flows (CNFs) are an attractive generative modeling technique, but they have been held back by limitations in their si… (see more)mulation-based maximum likelihood training. We introduce the generalized \textit{conditional flow matching} (CFM) technique, a family of simulation-free training objectives for CNFs. CFM features a stable regression objective like that used to train the stochastic flow in diffusion models but enjoys the efficient inference of deterministic flow models. In contrast to both diffusion models and prior CNF training algorithms, CFM does not require the source distribution to be Gaussian or require evaluation of its density. A variant of our objective is optimal transport CFM (OT-CFM), which creates simpler flows that are more stable to train and lead to faster inference, as evaluated in our experiments. Furthermore, OT-CFM is the first method to compute dynamic OT in a simulation-free way. Training CNFs with CFM improves results on a variety of conditional and unconditional generation tasks, such as inferring single cell dynamics, unsupervised image translation, and Schrödinger bridge inference.

2024-03-10

TMLR (accepted)

Learning and Aligning Structured Random Feature Networks

Vivian White

Muawiz Sajjad Chaudhary

Guillaume Lajoie

Kameron Decker Harris

Artificial neural networks (ANNs) are considered "black boxes'' due to the difficulty of interpreting their learned weights. While choosing… (see more) the best features is not well understood, random feature networks (RFNs) and wavelet scattering ground some ANN learning mechanisms in function space with tractable mathematics. Meanwhile, the genetic code has evolved over millions of years, shaping the brain to develop variable neural circuits with reliable structure that resemble RFNs. We explore a similar approach, embedding neuro-inspired, wavelet-like weights into multilayer RFNs. These can outperform scattering and have kernels that describe their function space at large width. We build learnable and deeper versions of these models where we can optimize separate spatial and channel covariances of the convolutional weight distributions. We find that these networks can perform comparatively with conventional ANNs while dramatically reducing the number of trainable parameters. Channel covariances are most influential, and both weight and activation alignment are needed for classification performance. Our work outlines how neuro-inspired configurations may lead to better performance in key cases and offers a potentially tractable reduced model for ANN learning.

2024-03-01

ICLR.cc/2024/Workshop/Re-Align (poster)

Generalization of deep learning models for hepatic steatosis grading using B-mode ultrasound images

Pedro Vianna

Yue Qi

Michael Chassé

An Tang

Guy Cloutier

Grayscale ultrasound remains a key modality for screening of hepatic steatosis due to its non-invasiveness and availability. While neural ne… (see more)tworks have shown promise in this field, their main drawback lies in their inability to generalize to diverse real-world settings. Variations in equipment, acquisition parameters, or population significantly affect model performance. Test-time adaptation, an unsupervised domain adaptation technique, overcomes these limitations by adjusting trained models during inference. Our retrospective study used two datasets collected in separate populations, with different scanners and protocols. We propose an adaptation method, using test-time batch normalization to selectively adjust BatchNorm layers based on test data for predicting steatosis grades. Comparing the non-adapted and adapted models, the mean absolute error (± standard deviation) in grading four severities of steatosis decreased from 0.92 ± 0.21 to 0.64 ± 0.22 . Specifically, for detection of steatosis the area under the curve increased from 0.76 ± 0.05 to 0.95 ± 0.02 when using the adapted model. Adapted models show promising results in improving performance compared to base models when testing data differ significantly from training data. Results suggest that the proposed method effectively addresses domain shift in diagnosing fatty liver using ultrasound images, reducing risks associated with deploying trained models.

2024-02-29

The Journal of the Acoustical Society of America (published)

Enhancing Supervised Visualization Through Autoencoder and Random Forest Proximities for Out-of-Sample Extension

Shuang Ni

Adrien Aumon

Kevin R. Moon

Jake S. Rhodes

The value of supervised dimensionality reduction lies in its ability to uncover meaningful connections between data features and labels. Com… (see more)mon dimensionality reduction methods embed a set of fixed, latent points, but are not capable of generalizing to an unseen test set. In this paper, we provide an out-of-sample extension method for the random forest-based supervised dimensionality reduction method, RF-PHATE, combining information learned from the random forest model with the function-learning capabilities of autoencoders. Through quantitative assessment of various autoencoder architectures, we identify that networks that reconstruct random forest proximities are more robust for the embedding extension problem. Furthermore, by leveraging proximity-based prototypes, we achieve a 40% reduction in training time without compromising extension quality. Our method does not require label information for out-of-sample points, thus serving as a semi-supervised method, and can achieve consistent quality using only 10% of the training data.

2023-12-31

MLSP (published)