Yue Li

Claris Gu

Maîtrise recherche - McGill

jia.gu@mail.mcgill.ca

Eric Huang

Maîtrise recherche - McGill

eric.huang@mila.quebec

Yixuan Li

Doctorat - McGill

Superviseur⋅e principal⋅e :

dylan.mann-krzisnik@mila.quebec

yixuan.li@mila.quebec

Dylan Mann-Krzisnik

Doctorat - McGill

Marshall Meng

Maîtrise recherche - McGill

Superviseur⋅e principal⋅e :

adrien.osakwe@mila.quebec

qiushi.meng@mila.quebec

Adrien Osakwe

Doctorat - McGill

vishvak.raghavan@mila.quebec

Google Scholar

Vishvak Raghavan

Doctorat - McGill

Co-superviseur⋅e :

Jun Ding

Jack Song

Maîtrise recherche - McGill

Co-superviseur⋅e :

junyi.song@mila.quebec

Ruilin Wang

Maîtrise recherche - McGill

ruilin.wang@mila.quebec

Bo-Hong Wang

Maîtrise recherche - McGill

bo-hong.wang@mila.quebec

Kunpeng Xu

Postdoctorat - McGill

Co-superviseur⋅e :

kunpeng.xu@mila.quebec

Publications

A Unified Solution to Diverse Heterogeneities in One-Shot Federated Learning

Jun Bai

Yiliao Song

Di Wu

Atul Sajjanhar

Yong Xiang

Wei Zhou

Xiaohui Tao

Yan Li

One-Shot Federated Learning (OSFL) restricts communication between the server and clients to a single round, significantly reducing communic… (voir plus)ation costs and minimizing privacy leakage risks compared to traditional Federated Learning (FL), which requires multiple rounds of communication. However, existing OSFL frameworks remain vulnerable to distributional heterogeneity, as they primarily focus on model heterogeneity while neglecting data heterogeneity. To bridge this gap, we propose FedHydra, a unified, data-free, OSFL framework designed to effectively address both model and data heterogeneity. Unlike existing OSFL approaches, FedHydra introduces a novel two-stage learning mechanism. Specifically, it incorporates model stratification and heterogeneity-aware stratified aggregation to mitigate the challenges posed by both model and data heterogeneity. By this design, the data and model heterogeneity issues are simultaneously monitored from different aspects during learning. Consequently, FedHydra can effectively mitigate both issues by minimizing their inherent conflicts. We compared FedHydra with five SOTA baselines on four benchmark datasets. Experimental results show that our method outperforms the previous OSFL methods in both homogeneous and heterogeneous settings. The code is available at https://github.com/Jun-B0518/FedHydra.

2025-08-02

Proceedings of the 31st ACM SIGKDD Conference on Knowledge Discovery and Data Mining V.2 (publié)

arxiv.org

Harnessing agent-based frameworks in CellAgentChat to unravel cell–cell interactions from single-cell and spatial transcriptomics

Vishvak Raghavan

Yumin Zheng

Jun Ding

Understanding cell–cell interactions (CCIs) is essential yet challenging owing to the inherent intricacy and diversity of cellular dynamic… (voir plus)s. Existing approaches often analyze global patterns of CCIs using statistical frameworks, missing the nuances of individual cell behavior owing to their focus on aggregate data. This makes them insensitive in complex environments where the detailed dynamics of cell interactions matter. We introduce CellAgentChat, an agent-based model (ABM) designed to decipher CCIs from single-cell RNA sequencing and spatial transcriptomics data. This approach models biological systems as collections of autonomous agents governed by biologically inspired principles and rules. Validated across eight diverse single-cell data sets, CellAgentChat demonstrates its effectiveness in detecting intricate signaling events across different cell populations. Moreover, CellAgentChat offers the ability to generate animated visualizations of single-cell interactions and provides flexibility in modifying agent behavior rules, facilitating thorough exploration of both close and distant cellular communications. Furthermore, CellAgentChat leverages ABM features to enable intuitive in silico perturbations via agent rule modifications, facilitating the development of novel intervention strategies. This ABM method unlocks an in-depth understanding of cellular signaling interactions across various biological contexts, thereby enhancing in silico studies for cellular communication–based therapies.

2025-06-30

Genome Research (publié)

CellMemory: hierarchical interpretation of out-of-distribution cells using bottlenecked transformer

Qifei Wang

He Zhu

Yiwen Hu

Yanjie Chen

Yuwei Wang

Guochao Li

Yun Li

Jinfeng Chen

Xuegong Zhang

James Zou

Manolis Kellis

Dianbo Liu

Lan Jiang

Identifying the genetic and molecular drivers of phenotypic heterogeneity among individuals is vital for understanding human health and for … (voir plus)diagnosing, monitoring, and treating diseases. To this end, international consortia such as the Human Cell Atlas and the Tabula Sapiens are creating comprehensive cellular references. Due to the massive volume of data generated, machine learning methods, especially transformer architectures, have been widely employed in related studies. However, applying machine learning to cellular data presents several challenges. One such challenge is making the methods interpretable with respect to both the input cellular information and its context. Another less explored challenge is the accurate representation of cells outside existing references, referred to as out-of-distribution (OOD) cells. The out-of-distribution could be attributed to various physiological conditions, such as comparing diseased cells, particularly tumor cells, with healthy reference data, or significant technical variations, such as using transfer learning from single-cell reference to spatial query data. Inspired by the global workspace theory in cognitive neuroscience, we introduce CellMemory, a bottlenecked Transformer with improved generalization capabilities designed for the hierarchical interpretation of OOD cells unseen during reference building. Even without pre-training, it exceeds the performance of large language models pre-trained with tens of millions of cells. In particular, when deciphering spatially resolved single-cell transcriptomics data, CellMemory demonstrates the ability to interpret data at the granule level accurately. Finally, we harness CellMemory's robust representational capabilities to elucidate malignant cells and their founder cells in different patients, providing reliable characterizations of the cellular changes caused by the disease.

2025-06-22

Genome Biology (publié)

FedWeight: mitigating covariate shift of federated learning on electronic health records data through patients re-weighting

He Zhu

Jun Bai

Na Li

Xiaoxiao Li

Dianbo Liu

David L. Buckeridge

Federated learning (FL) enables collaborative analysis of decentralized medical data while preserving patient privacy. However, the covariat… (voir plus)e shift from demographic and clinical differences can reduce model generalizability. We propose FedWeight, a novel FL framework that mitigates covariate shift by reweighting patient data from the source sites using density estimators, allowing the trained model to better align with the distribution of the target site. To support unsupervised applications, we introduce FedWeight ETM, a federated embedded topic model. We evaluated FedWeight in cross-site FL on the eICU dataset and cross-dataset FL between eICU and MIMIC III. FedWeight consistently outperforms standard FL baselines in predicting ICU mortality, ventilator use, sepsis diagnosis, and length of stay. SHAP-based interpretation and ETM-based topic modeling reveal improved identification of clinically relevant characteristics and disease topics associated with ICU readmission.

2025-05-16

NPJ Digital Medicine (publié)

ECLARE: multi-teacher contrastive learning via ensemble distillation for diagonal integration of single-cell multi-omic data

Dylan Mann-Krzisnik

Anjali Chawla

Gustavo Turecki

Corina Nagy

Integrating multimodal single-cell data such as scRNA-seq with scATAC-seq is essential for decoding gene regulatory networks, but remains di… (voir plus)fficult due to feature harmonization and limited paired multiome data. We introduce ECLARE, a framework that uses multi-teacher ensemble knowledge distillation with contrastive learning and optimal-transport alignment to integrate unpaired single-cell multi-omic datasets. Across benchmarks, ECLARE achieves competitive performance for multimodal integration and biological structure preservation. We further demonstrate utility in a major depressive disorder case study using unpaired snRNA-seq and snATAC-seq, identifying transcription factor–target gene programs that are differentially regulated with sex- and cell-type specificity. Finally, ECLARE learns continuous representations that capture longitudinal structure, highlighting altered neurodevelopmental programs associated with depression in female subjects. Altogether, ECLARE expands the practical reach of multimodal single-cell analysis by enabling diagonal integration of unpaired data with strong biological preservation, facilitating integrative regulatory studies across diverse cohorts and conditions.

2025-04-06

bioRxiv (prépublication)

TrajGPT: Irregular Time-Series Representation Learning of Health Trajectory

Ziyang Song

Qincheng Lu

He Zhu

David Buckeridge

In the healthcare domain, time-series data are often irregularly sampled with varying intervals through outpatient visits, posing challenges… (voir plus) for existing models designed for equally spaced sequential data. To address this, we propose Trajectory Generative Pre-trained Transformer (TrajGPT) for representation learning on irregularly-sampled healthcare time series. TrajGPT introduces a novel Selective Recurrent Attention (SRA) module that leverages a data-dependent decay to adaptively filter irrelevant past information. As a discretized ordinary differential equation (ODE) framework, TrajGPT captures underlying continuous dynamics and enables a time-specific inference for forecasting arbitrary target timesteps without auto-regressive prediction. Experimental results based on the longitudinal EHR data PopHR from Montreal health system and eICU from PhysioNet showcase TrajGPT's superior zero-shot performance in disease forecasting, drug usage prediction, and sepsis detection. The inferred trajectories of diabetic and cardiac patients reveal meaningful comorbidity conditions, underscoring TrajGPT as a useful tool for forecasting patient health evolution.

2024-12-31

IEEE Journal of Biomedical and Health Informatics (inconnu)

Cell ontology guided transcriptome foundation model

Manqi Zhou

Boyu Han

Transcriptome foundation models (TFMs) hold great promises of deciphering the transcriptomic language that dictate diverse cell functions by… (voir plus) self-supervised learning on large-scale single-cell gene expression data, and ultimately unraveling the complex mechanisms of human diseases. However, current TFMs treat cells as independent samples and ignore the taxonomic relationships between cell types, which are available in cell ontology graphs. We argue that effectively leveraging this ontology information during the TFM pre-training can improve learning biologically meaningful gene co-expression patterns while preserving TFM as a general purpose foundation model for downstream zero-shot and fine-tuning tasks. To this end, we present **s**ingle **c**ell, **Cell**-**o**ntology guided TFM (scCello). We introduce cell-type coherence loss and ontology alignment loss, which are minimized along with the masked gene expression prediction loss during the pre-training. The novel loss component guide scCello to learn the cell-type-specific representation and the structural relation between cell types from the cell ontology graph, respectively. We pre-trained scCello on 22 million cells from CellxGene database leveraging their cell-type labels mapped to the cell ontology graph from Open Biological and Biomedical Ontology Foundry. Our TFM demonstrates competitive generalization and transferability performance over the existing TFMs on biologically important tasks including identifying novel cell types of unseen cells, prediction of cell-type-specific marker genes, and cancer drug responses. Source code and model weights are available at https://github.com/DeepGraphLearning/scCello.

2024-12-10

Neural Information Processing Systems (Accept (spotlight))

openreview.net

MixEHR-Nest: Identifying Subphenotypes within Electronic Health Records through Hierarchical Guided-Topic Modeling

Ruohan Wang

Zilong Wang

Ziyang Song

David Buckeridge

Automatic subphenotyping from electronic health records (EHRs)provides numerous opportunities to understand diseases with unique subgroups a… (voir plus)nd enhance personalized medicine for patients. However, existing machine learning algorithms either focus on specific diseases for better interpretability or produce coarse-grained phenotype topics without considering nuanced disease patterns. In this study, we propose a guided topic model, MixEHR-Nest, to infer sub-phenotype topics from thousands of disease using multi-modal EHR data. Specifically, MixEHR-Nest detects multiple subtopics from each phenotype topic, whose prior is guided by the expert-curated phenotype concepts such as Phenotype Codes (PheCodes) or Clinical Classification Software (CCS) codes. We evaluated MixEHR-Nest on two EHR datasets: (1) the MIMIC-III dataset consisting of over 38 thousand patients from intensive care unit (ICU) from Beth Israel Deaconess Medical Center (BIDMC) in Boston, USA; (2) the healthcare administrative database PopHR, comprising 1.3 million patients from Montreal, Canada. Experimental results demonstrate that MixEHR-Nest can identify subphenotypes with distinct patterns within each phenotype, which are predictive for disease progression and severity. Consequently, MixEHR-Nest distinguishes between type 1 and type 2 diabetes by inferring subphenotypes using CCS codes, which do not differentiate these two subtype concepts. Additionally, MixEHR-Nest not only improved the prediction accuracy of short-term mortality of ICU patients and initial insulin treatment in diabetic patients but also revealed the contributions of subphenotypes. For longitudinal analysis, MixEHR-Nest identified subphenotypes of distinct age prevalence under the same phenotypes, such as asthma, leukemia, epilepsy, and depression. The MixEHR-Nest software is available at GitHub: https://github.com/li-lab-mcgill/MixEHR-Nest.

2024-11-21

Proceedings of the 15th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics (publié)

arxiv.org

scMoE: single-cell mixture of experts for learning hierarchical, cell-type-specific, and interpretable representations from heterogeneous scRNA-seq data

Michael Huang

Advancements in single-cell transcriptomics methods have resulted in a wealth of single-cell RNA sequencing (scRNA-seq) data. Methods to lea… (voir plus)rn cell representation from atlas-level scRNA-seq data across diverse tissues can shed light into cell functions implicated in diseases such as cancer. However, integrating large-scale and heterogeneous scRNA-seq data is challenging due to the disparity of cell-types and batch effects. We present single-cell Mixture of Expert (scMoE), a hierarchical mixture of experts single-cell topic model. Our key contributions are the cell-type specific experts, which explicitly aligns topics with cell-types, and the integration of hierarchical cell-type lineages and domain knowledge. scMoE is both transferable and highly interpretable. We benchmarked our scMoE’s performance on 9 single-cell RNA-seq datasets for clustering and 3 simulated spatial datasets for spatial deconvolution. We additionally show that our model, using single-cell references, yields meaningful biological results by deconvolving 3 cancer bulk RNA-seq datasets and 2 spatial transcriptomics datasets. scMoE is able to identify cell-types of survival importance, find cancer subtype specific deconvolutional patterns, and capture meaningful spatially distinct cell-type distributions.

2024-11-21

Proceedings of the 15th ACM International Conference on Bioinformatics, Computational Biology and Health Informatics (publié)

Protocol to perform integrative analysis of high-dimensional single-cell multimodal data using an interpretable deep learning technique

Manqi Zhou

Hao Zhang

Zilong Bai

Dylan Mann-Krzisnik

Fei Wang

2024-05-31

STAR Protocols (publié)

GFETM: Genome Foundation-based Embedded Topic Model for scATAC-seq Modeling

Yimin Fan

Shi Han

Single-cell Assay for Transposase-Accessible Chromatin with sequencing (scATAC-seq) has emerged as a powerful technique for investigating op… (voir plus)en chromatin landscapes at single-cell resolution. However, analyzing scATAC-seq data remain challenging due to its sparsity and noise. Genome Foundation Models (GFMs), pre-trained on massive DNA sequences, have proven effective at genome analysis. Given that open chromatin regions (OCRs) harbour salient sequence features, we hypothesize that leveraging GFMs’ sequence embeddings can improve the accuracy and generalizability of scATAC-seq modeling. Here, we introduce the Genome Foundation Embedded Topic Model (GFETM), an interpretable deep learning framework that combines GFMs with the Embedded Topic Model (ETM) for scATAC-seq data analysis. By integrating the DNA sequence embeddings extracted by a GFM from OCRs, GFETM demonstrates superior accuracy and generalizability and captures cell-state specific TF activity both with zero-shot inference and attention mechanism analysis. Finally, the topic mixtures inferred by GFETM reveal biologically meaningful epigenomic signatures of kidney diabetes.

2024-05-16

Conference on Research in Computational Molecular Biology (publié)

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

Liam Hodgson

Yasser Iturria-Medina

Jo Anne Stratton

Guy Wolf

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… (voir plus). 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 (publié)