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

Geometric Scattering Attention Networks

Yimeng Min

Frederik Wenkel

Geometric scattering has recently gained recognition in graph representation learning, and recent work has shown that integrating scattering… (see more) features in graph convolution networks (GCNs) can alleviate the typical oversmoothing of features in node representation learning. However, scattering often relies on handcrafted design, requiring careful selection of frequency bands via a cascade of wavelet transforms, as well as an effective weight sharing scheme to combine low- and band-pass information. Here, we introduce a new attention-based architecture to produce adaptive task-driven node representations by implicitly learning node-wise weights for combining multiple scattering and GCN channels in the network. We show the resulting geometric scattering attention network (GSAN) outperforms previous networks in semi-supervised node classification, while also enabling a spectral study of extracted information by examining node-wise attention weights.

2021-12-31

IEEE International Conference on Acoustics, Speech and Signal Processing (unknown)

Goal-driven optimization of single-neuron properties in artiﬁcial networks reveals regularization role of neural diversity and adaptation in the brain

Neurons in the brain have rich and adaptive input-output properties. Features such as diverse f-I curves and spike frequency adaptation are … (see more)known to place single neurons in optimal coding regimes when facing changing stimuli. Yet, it is still unclear how brain circuits exploit single neuron ﬂexibility, and how network-level requirements may have shaped such cellular function. To answer this question, a multi-scaled approach is needed where the computations of single neurons and of neural circuits must be considered as a complete system. In this work, we use artiﬁcial neural networks to systematically investigate single neuron input-output adaptive mechanisms, optimized in an end-to-end fashion. Throughout the optimization process, each neuron has the liberty to modify its nonlinear activation function, parametrized to mimic f-I curves of biological neurons, and to learn adaptation strategies to modify activation functions in real-time during a task. We ﬁnd that such networks show much-improved robustness to noise and changes in input statistics. Importantly, we ﬁnd that this procedure recovers precise coding strategies found in biological neurons, such as gain scaling and fractional order differentiation/integration. Using tools from dynamical systems theory, we analyze the role of these emergent single neuron properties and argue that neural diversity and adaptation plays an active regularization role that enables neural circuits to optimally propagate information across time.

2021-12-31

(published)

www.semanticscholar.org

Patient health records and whole viral genomes from an early SARS-CoV-2 outbreak in a Quebec hospital reveal features associated with favorable outcomes

Bastien Paré

Marieke Rozendaal

Sacha Morin

Raphaël Poujol

Fatima Mostefai

Shawn M. Simpson

Jean-Christophe Grenier

Léa Kaufmann

Henry Xing

Miguelle Sanchez

Ariane Yechouron

Ronald Racette

Julie G. Hussin

Ivan Pavlov

Martin A. Smith

The first confirmed case of COVID-19 in Quebec, Canada, occurred at Verdun Hospital on February 25, 2020. A month later, a localized outbrea… (see more)k was observed at this hospital. We performed tiled amplicon whole genome nanopore sequencing on nasopharyngeal swabs from all SARS-CoV-2 positive samples from 31 March to 17 April 2020 in 2 local hospitals to assess the viral diversity of the outbreak. We report 264 viral genomes from 242 individuals (both staff and patients) with associated clinical features and outcomes, as well as longitudinal samples, technical replicates and the first publicly disseminated SARS-CoV-2 genomes in Quebec. Viral lineage assessment identified multiple subclades in both hospitals, with a predominant subclade in the Verdun outbreak, indicative of hospital-acquired transmission. Dimensionality reduction identified two subclades that evaded supervised lineage assignment methods, including Pangolin, and identified certain symptoms (headache, myalgia and sore throat) that are significantly associated with favorable patient outcomes. We also address certain limitations of standard SARS-CoV-2 bioinformatics procedures, notably when presented with multiple viral haplotypes.

2021-12-01

PLOS ONE (published)

Fixing Bias in Reconstruction-Based Anomaly Detection with Lipschitz Discriminators

Anomaly detection is of great interest in fields where abnormalities need to be identified and corrected (e.g., medicine and finance). Deep … (see more)learning methods for this task often rely on autoencoder reconstruction error, sometimes in conjunction with other errors. We show that this approach exhibits intrinsic biases that lead to undesirable results. Reconstruction-based methods are sensitive to training-data outliers and simple-to-reconstruct points. Instead, we introduce a new unsupervised Lipschitz anomaly discriminator that does not suffer from these biases. Our anomaly discriminator is trained, similar to the ones used in GANs, to detect the difference between the training data and corruptions of the training data. We show that this procedure successfully detects unseen anomalies with guarantees on those that have a certain Wasserstein distance from the data or corrupted training set. These additions allow us to show improved performance on MNIST, CIFAR10, and health record data.

2021-11-27

Journal of Signal Processing Systems (unknown)

Data-Driven Learning of Geometric Scattering Modules for GNNs

Frederick Wenkel

Kincaid MacDonald

We propose a new graph neural network (GNN) module, based on relaxations of recently proposed geometric scattering transforms, which consist… (see more) of a cascade of graph wavelet filters. Our learnable geometric scattering (LEGS) module enables adaptive tuning of the wavelets to encourage band-pass features to emerge in learned representations. The incorporation of our LEGS-module in GNNs enables the learning of longer-range graph relations compared to many popular GNNs, which often rely on encoding graph structure via smoothness or similarity between neighbors. Further, its wavelet priors result in simplified architectures with significantly fewer learned parameters compared to competing GNNs. We demonstrate the predictive performance of LEGS-based networks on graph classification benchmarks, as well as the descriptive quality of their learned features in biochemical graph data exploration tasks.

2021-10-24

PubMed Central (accepted)

Multimodal Data Visualization and Denoising with Integrated Diffusion

Manik Kuchroo

Abhinav Godavarthi

We propose a method called integrated diffusion for combining multimodal datasets, or data gathered via several different measurements on th… (see more)e same system, to create a joint data diffusion operator. As real world data suffers from both local and global noise, we introduce mechanisms to optimally calculate a diffusion operator that reflects the combined information from both modalities. We show the utility of this joint operator in data denoising, visualization and clustering, performing better than other methods to integrate and analyze multimodal data. We apply our method to multi-omic data generated from blood cells, measuring both gene expression and chromatin accessibility. Our approach better visualizes the geometry of the joint data, captures known cross-modality associations and identifies known cellular populations. More generally, integrated diffusion is broadly applicable to multimodal datasets generated in many medical and biological systems.

2021-10-24

PubMed Central (accepted)

Data-driven approaches for genetic characterization of SARS-CoV-2 lineages

Fatima Mostefai

Isabel Gamache

Jessie Huang

Arnaud N’Guessan

Justin Pelletier

Ahmad Pesaranghader

David Hamelin

Carmen Lia Murall

Raphaël Poujol

Jean-Christophe Grenier

Martin Smith

Etienne Caron

Morgan Craig

Jesse Shapiro

Julie G. Hussin

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19)… (see more), has been sequenced at an unprecedented scale, leading to a tremendous amount of viral genome sequencing data. To understand the evolution of this virus in humans, and to assist in tracing infection pathways and designing preventive strategies, we present a set of computational tools that span phylogenomics, population genetics and machine learning approaches. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic, using 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets, enabling real-time analyses. Furthermore, time series change of Tajima’s D provides a powerful metric of population expansion. Unsupervised learning techniques further highlight key steps in variant detection and facilitate the study of the role of this genomic variation in the context of SARS-CoV-2 infection, with Multiscale PHATE methodology identifying fine-scale structure in the SARS-CoV-2 genetic data that underlies the emergence of key lineages. The computational framework presented here is useful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of worldwide populations of humans and other organisms.

2021-09-28

BioRxiv (preprint)

Diffusion Earth Mover's Distance and Distribution Embeddings

Guillaume Huguet

Amine Natik

Kincaid MacDonald

Manik Kuchroo

Ronald R. Coifman

We propose a new fast method of measuring distances between large numbers of related high dimensional datasets called the Diffusion Earth Mo… (see more)ver's Distance (EMD). We model the datasets as distributions supported on common data graph that is derived from the affinity matrix computed on the combined data. In such cases where the graph is a discretization of an underlying Riemannian closed manifold, we prove that Diffusion EMD is topologically equivalent to the standard EMD with a geodesic ground distance. Diffusion EMD can be computed in

2021-07-19

International Conference on Machine Learning (Spotlight)

proceedings.mlr.press

Random Forest-Based Diffusion Information Geometry for Supervised Visualization and Data Exploration

Jake S. Rhodes

Adele Cutler

Kevin R. Moon

Most dimensionality reduction techniques to date are unsupervised; they do not take class labels into account (e.g., PCA, MDS, t-SNE, Isomap… (see more)). Such methods require large amounts of data and are often sensitive to noise that may obfuscate important patterns in the data. Various attempts at supervised dimensionality reduction methods that take into account auxiliary annotations (e.g., class labels) have been successfully implemented with goals of increased classification accuracy or improved data visualization. In this paper, we describe a novel supervised visualization technique based on random forest proximities and a diffusion-based information geometry. We show, both qualitatively and quantitatively, the advantages of our approach in retaining local and global structure in data, while demonstrating the spatial relevance of features important for the supervised task. Importantly, our approach is robust to noise and parameter tuning, thus making it simple to use while producing reliable visualizations for data exploration.

2021-07-10

Symposium on Software Performance (published)

Topological analysis of single-cell data reveals shared glial landscape of macular degeneration and neurodegenerative diseases

Manik Kuchroo

Marcello DiStasio

Eda Calapkulu

Maryam Ige

Le Zhang

Amar H. Sheth

Madhvi Menon

Yu Xing

Scott Gigante

Jessie Huang

Rahul M. Dhodapkar

Bastian Rieck

Brian P. Hafler

1 A novel topological machine learning approach applied to single-nucleus RNA sequencing from human retinas… (see more) with age-related macular degeneration identifies interacting disease phase-specific glial activation states shared with Alzheimer’s disease and multiple sclerosis. 2 Neurodegeneration occurs in a wide range of diseases, including age-related macular degeneration (AMD), Alzheimer’s disease (AD), and multiple sclerosis (MS), each with distinct inciting events. To determine whether glial transcriptional states are shared across phases of degeneration, we sequenced 50,498 nuclei from the retinas of seven AMD patients and six healthy controls, generating the first single-cell transcriptomic atlas of AMD. We identified groupings of cells implicated in disease pathogenesis by applying a novel topologically-inspired machine learning approach called ‘diffusion condensation.’ By calculating diffusion homology features and performing persistence analysis, diffusion condensation identified activated glial states enriched in the early phases of AMD, AD, and MS as well as an AMD-specific proangiogenic astrocyte state promoting pathogenic neovascularization in advanced AMD. Finally, by mapping the expression of disease-associated genes to glial states, we identified key signaling interactions creating hypotheses for therapeutic intervention. Our topological analysis identified an integrated disease-phase specific glial landscape that is shared across neurodegenerative conditions affecting the central nervous system.

2021-01-19

bioRxiv (preprint)

Extendable and invertible manifold learning with geometry regularized autoencoders

Andrés F. Duque

Sacha Morin

Kevin Moon

A fundamental task in data exploration is to extract simplified low dimensional representations that capture intrinsic geometry in data, esp… (see more)ecially for faithfully visualizing data in two or three dimensions. Common approaches to this task use kernel methods for manifold learning. However, these methods typically only provide an embedding of fixed input data and cannot extend to new data points. Autoencoders have also recently become popular for representation learning. But while they naturally compute feature extractors that are both extendable to new data and invertible (i.e., reconstructing original features from latent representation), they have limited capabilities to follow global intrinsic geometry compared to kernel-based manifold learning. We present a new method for integrating both approaches by incorporating a geometric regularization term in the bottleneck of the autoencoder. Our regularization, based on the diffusion potential distances from the recently-proposed PHATE visualization method, encourages the learned latent representation to follow intrinsic data geometry, similar to manifold learning algorithms, while still enabling faithful extension to new data and reconstruction of data in the original feature space from latent coordinates. We compare our approach with leading kernel methods and autoencoder models for manifold learning to provide qualitative and quantitative evidence of our advantages in preserving intrinsic structure, out of sample extension, and reconstruction. Our method is easily implemented for big-data applications, whereas other methods are limited in this regard.

2020-12-31

IEEE International Conference on Big Data (unknown)

Finding Archetypal Spaces Using Neural Networks

David van Dijk

Daniel B. Burkhardt

Matthew Amodio

Archetypal analysis is a data decomposition method that describes each observation in a dataset as a convex combination of "pure types" or a… (see more)rchetypes. These archetypes represent extrema of a data space in which there is a trade-off between features, such as in biology where different combinations of traits provide optimal fitness for different environments. Existing methods for archetypal analysis work well when a linear relationship exists between the feature space and the archetypal space. However, such methods are not applicable to systems where the feature space is generated non-linearly from the combination of archetypes, such as in biological systems or image transformations. Here, we propose a reformulation of the problem such that the goal is to learn a non-linear transformation of the data into a latent archetypal space. To solve this problem, we introduce Archetypal Analysis network (AAnet), which is a deep neural network framework for learning and generating from a latent archetypal representation of data. We demonstrate state-of-the-art recovery of ground-truth archetypes in non-linear data domains, show AAnet can generate from data geometry rather than from data density, and use AAnet to identify biologically meaningful archetypes in single-cell gene expression data.

2020-12-31

IEEE International Conference on Big Data (unknown)