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Guillaume Huguet

PhD - Université de Montréal
Supervisor
Guy Wolf
Research Topics
Computational Biology
Generative Models
Spectral Learning
Google Scholar
GitHub

Publications

Single-cell analysis reveals inflammatory interactions driving macular degeneration
Manik Kuchroo
Marcello DiStasio
Eric Song
Eda Calapkulu
Le Zhang
Maryam Ige
Amar H. Sheth
Abdelilah Majdoubi
Madhvi Menon
Alexander Tong
Abhinav Godavarthi
Yu Xing
Scott Gigante
Holly Steach
Jessie Huang
Jessie Huang
Guillaume Huguet
Janhavi Narain
Kisung You
George Mourgkos … (see 6 more)
Rahul M. Dhodapkar
Matthew J. Hirn
Bastian Rieck
Guy Wolf
Smita Krishnaswamy
Brian P. Hafler
Due to commonalities in pathophysiology, age-related macular degeneration (AMD) represents a uniquely accessible model to investigate thera… (see more)pies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 11 postmortem human retinas with age-related macular degeneration and 6 control retinas with no history of retinal disease. We create a machine-learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer’s disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1β which drives angiogenesis characteristic of disease pathogenesis. We validated this mechanism using in vitro and in vivo assays in mouse, identifying a possible new therapeutic target for AMD and possibly other neurodegenerative conditions. Thus, due to shared glial states, the retina provides a potential system for investigating therapeutic approaches in neurodegenerative diseases.
2023-05-04
Nature Communications (published)
doi.org
Using rare genetic mutations to revisit structural brain asymmetry
Jakub Kopal
Kuldeep Kumar
Kimia Shafighi
Karin Saltoun
Claudia Modenato
Clara A. Moreau
Guillaume Huguet
Martineau Jean-Louis
Charles-Olivier Martin
Charles-Olivier Martin
Zohra Saci
Nadine Younis
Elise Douard
Khadije Jizi
Alexis Beauchamp-Chatel
Leila Kushan
Ana I. Silva
Marianne B. M. van den Bree
David E. J. Linden
Michael J. Owen … (see 11 more)
Jeremy Hall
Sarah Lippé
Bogdan Draganski
Ida E. Sønderby
Ole A. Andreassen
David C. Glahn
Paul M. Thompson
Carrie E. Bearden
Robert Zatorre
Sébastien Jacquemont
Danilo Bzdok
Asymmetry between the left and right brain is a key feature of brain organization. Hemispheric functional specialization underlies some of t… (see more)he most advanced human-defining cognitive operations, such as articulated language, perspective taking, or rapid detection of facial cues. Yet, genetic investigations into brain asymmetry have mostly relied on common variant studies, which typically exert small effects on brain phenotypes. Here, we leverage rare genomic deletions and duplications to study how genetic alterations reverberate in human brain and behavior. We quantitatively dissected the impact of eight high-effect-size copy number variations (CNVs) on brain asymmetry in a multi-site cohort of 552 CNV carriers and 290 non-carriers. Isolated multivariate brain asymmetry patterns spotlighted regions typically thought to subserve lateralized functions, including language, hearing, as well as visual, face and word recognition. Planum temporale asymmetry emerged as especially susceptible to deletions and duplications of specific gene sets. Targeted analysis of common variants through genome-wide association study (GWAS) consolidated partly diverging genetic influences on the right versus left planum temporale structure. In conclusion, our gene-brain-behavior mapping highlights the consequences of genetically controlled brain lateralization on human-defining cognitive traits.
2023-04-17
bioRxiv (preprint)
doi.org
Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence
Jakub Kopal
Kuldeep Kumar
Karin Saltoun
Claudia Modenato
Clara A. Moreau
Sandra Martin-Brevet
Guillaume Huguet
Martineau Jean-Louis
Charles-Olivier Martin
Charles-Olivier Martin
Zohra Saci
Nadine Younis
Petra Tamer
Elise Douard
Anne M. Maillard
Borja Rodriguez-Herreros
Aurélie Pain
Sonia Richetin
Leila Kushan
Ana I. Silva … (see 13 more)
Marianne B. M. van den Bree
David E. J. Linden
Michael J. Owen
Jeremy Hall
Sarah Lippé
Bogdan Draganski
Ida E. Sønderby
Ole A. Andreassen
David C. Glahn
Paul M. Thompson
Carrie E. Bearden
Sébastien Jacquemont
Danilo Bzdok
Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleio… (see more)tropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts. It remains unknown, for example, how distinct CNVs escalate vulnerability for the same developmental and psychiatric disorders. Here we quantitatively dissect the associations between brain organization and behavioural differentiation across 8 key CNVs. In 534 CNV carriers, we explored CNV-specific brain morphology patterns. CNVs were characteristic of disparate morphological changes involving multiple large-scale networks. We extensively annotated these CNV-associated patterns with ~1,000 lifestyle indicators through the UK Biobank resource. The resulting phenotypic profiles largely overlap and have body-wide implications, including the cardiovascular, endocrine, skeletal and nervous systems. Our population-level investigation established brain structural divergences and phenotypical convergences of CNVs, with direct relevance to major brain disorders.
2023-03-01
Nature Human Behaviour (unknown)
doi.org
Conditional Flow Matching: Simulation-Free Dynamic Optimal Transport
Alexander Tong
Nikolay Malkin
Guillaume Huguet
Yanlei Zhang
Jarrid Rector-Brooks
Kilian Fatras
Guy Wolf
Yoshua Bengio
2022-12-31
arXiv.org (preprint)
doi.org
Geodesic Sinkhorn for Fast and Accurate Optimal Transport on Manifolds
Guillaume Huguet
Alexander Tong
María Ramos Zapatero
Christopher J. Tape
Guy Wolf
Smita Krishnaswamy
Efficient computation of optimal transport distance between distributions is of growing importance in data science. Sinkhorn-based methods a… (see more)re currently the state-of-the-art for such computations, but require
2022-12-31
2023 IEEE 33rd International Workshop on Machine Learning for Signal Processing (MLSP) (published)
doi.org
arxiv.org
A Heat Diffusion Perspective on Geodesic Preserving Dimensionality Reduction
Guillaume Huguet
Alexander Tong
Edward De Brouwer
Yanlei Zhang
Guy Wolf
Ian Adelstein
Smita Krishnaswamy
Diffusion-based manifold learning methods have proven useful in representation learning and dimensionality reduction of modern high dimensio… (see more)nal, high throughput, noisy datasets. Such datasets are especially present in fields like biology and physics. While it is thought that these methods preserve underlying manifold structure of data by learning a proxy for geodesic distances, no specific theoretical links have been established. Here, we establish such a link via results in Riemannian geometry explicitly connecting heat diffusion to manifold distances. In this process, we also formulate a more general heat kernel based manifold embedding method that we call heat geodesic embeddings. This novel perspective makes clearer the choices available in manifold learning and denoising. Results show that our method outperforms existing state of the art in preserving ground truth manifold distances, and preserving cluster structure in toy datasets. We also showcase our method on single cell RNA-sequencing datasets with both continuum and cluster structure, where our method enables interpolation of withheld timepoints of data. Finally, we show that parameters of our more general method can be configured to give results similar to PHATE (a state-of-the-art diffusion based manifold learning method) as well as SNE (an attraction/repulsion neighborhood based method that forms the basis of t-SNE).
2022-12-31
Advances in Neural Information Processing Systems 36 (NeurIPS 2023) (published)
doi.org
openreview.net
P397. Genomic Deletions and Duplications Show Mirror Effects on Cognitive Ability According to Spatial Patterns of Gene Expression in the Human Brain
Kuldeep Kumar
Sayeh Kazem
Guillaume Huguet
Elise Douard
Zohra Saci
Laura Almasy
David Glahn
Guillaume Dumas
Sébastien Jacquemont
2022-04-30
Biological Psychiatry (published)
doi.org
THE EFFECT SIZE OF GENES ON COGNITIVE ABILITIES IS LINKED TO THEIR EXPRESSION ALONG THE MAJOR HIERARCHICAL GRADIENT IN THE HUMAN BRAIN
Sébastien Jacquemont
Guillaume Huguet
Elise Douard
Zohra Saci
Guillaume Dumas
Laura Almasy
David C. Glahn
2021-09-30
European Neuropsychopharmacology (published)
doi.org
Embedding Signals on Graphs with Unbalanced Diffusion Earth Mover's Distance
Alexander Tong
Guillaume Huguet
Dennis Shung
Amine Natik
Manik Kuchroo
Guillaume Lajoie
Guy Wolf
Smita Krishnaswamy
In modern relational machine learning it is common to encounter large graphs that arise via interactions or similarities between observation… (see more)s in many domains. Further, in many cases the target entities for analysis are actually signals on such graphs. We propose to compare and organize such datasets of graph signals by using an earth mover's distance (EMD) with a geodesic cost over the underlying graph. Typically, EMD is computed by optimizing over the cost of transporting one probability distribution to another over an underlying metric space. However, this is inefficient when computing the EMD between many signals. Here, we propose an unbalanced graph EMD that efficiently embeds the unbalanced EMD on an underlying graph into an
2020-12-31
arXiv.org (preprint)
doi.org
arxiv.org
General Principles of Gene Dosage Effects on Brain Structure
Claudia Modenato
Kuldeep Kumar
Clara A. Moreau
Catherine Schramm
Guillaume Huguet
Sandra Martin-Brevet
Aurélie Pain
Anne M. Maillard
Sonia Richetin
Borja Rodriguez-Herreros
Lester Melie-Garcia
Ana Dos Santos Silva
Marianne B.M. van den Bree
David E.J. Linden
Carrie E. Bearden
Danilo Bzdok
Sarah Lippé
Mallar Chakravarty
Bogdan Draganski
Sébastien Jacquemont
2020-04-30
Biological Psychiatry (published)
doi.org
Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia
Clara A. Moreau
Sebastian G. W. Urchs
Pierre Orban
Catherine Schramm
Guillaume Dumas
Aurélie Labbe
Guillaume Huguet
Elise Douard
Pierre-Olivier Quirion
Amy Lin
Leila Kushan
Stephanie Grot
David Luck
Adrianna Mendrek
Stephane Potvin
Emmanuel Stip
Thomas Bourgeron
Alan C. Evans
Carrie E. Bearden
Pierre Bellec … (see 1 more)
Sébastien Jacquemont
16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Defic… (see more)it-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.
2019-12-05
bioRxiv (preprint)
doi.org