Yue Li

Alain Han

Baccalauréat - McGill

Yixuan Li

Doctorat - McGill

Superviseur⋅e principal⋅e :

Archer Yang

Dylan Mann-Krzisnik

Doctorat - McGill

Marshall Meng

Maîtrise recherche - McGill

Superviseur⋅e principal⋅e :

Doctorat - McGill

Maîtrise recherche - McGill

Co-superviseur⋅e :

Jun Ding

Ziyang Song

Doctorat - McGill

Wilbur Wang

Maîtrise recherche - McGill

Shadi Zabad

Doctorat - McGill

Caiya Zhang

Maîtrise recherche - McGill

He Zhu

Doctorat - McGill

Publications

Abstract 4142894: Multimorbidity Trajectories Across the Lifespan in Patients with Congenital Heart Disease

Chao Li

Aihua Liu

Solomon Bendayan

Liming Guo

Judith Therrien

Archer Yang

Robyn Tamblyn

Jay Brophy

Ariane Marelli

Background: Befitted from advances in medical care, patients with congenital heart disease (CHD) now survive to adulthood but face elevated… (voir plus) risks of both cardiac and non-cardiac complications. Understanding the trajectories of comorbidity development over a patient's lifespan is cornerstone to optimize care expected to improve long-term health outcomes. Research Aim: This study aims to investigate the temporal sequences and evolution of comorbidities in CHD patients across their lifespan. We hypothesize that multimorbidity trajectories in CHD patients are linked to CHD lesion severity and age at onset of specific comorbidities. Methods: Using the Quebec CHD database which comprised data in outpatient visits, hospitalization records and vital status from 1983 to 2017, we designed a longitudinal cohort study evaluating the development of 39 comorbidities coded using ICD-9/10. Temporal sequences were mapped using median age of onset. Associations between disease pairs were quantified by hazard ratios from Cox proportional hazard models adjusting for age, sex, genetic syndrome, competing risks of death, and taking into account the time-varying nature of the predictor diseases. Results: The cohort included 9,764 individuals with severe and 127,729 with non-severe CHD lesions. In severe CHD patients, most comorbidities developed between ages 25 and 40. Comorbidity progression began with childhood cardiovascular diseases, followed by systemic diseases such as diabetes, liver and kidney diseases, and advanced to heart failure and dementia in middle adulthood. In addition, mental disorders emerged in early adulthood and were associated with subsequent development of kidney diseases and dementia. Different trajectories were observed in non-severe CHD patients with 2-3 decades later disease onsets and non-differential onsets between cardiovascular and systemic complications (Figure). Conclusions: Distinct multimorbidity trajectories were observed in CHD patients by CHD lesion severity. In patients with severe CHD lesions, early systemic diseases significantly influenced subsequent complications. These findings highlight the need for well-timed surveillance guidelines and interventions to improve health outcomes.

2024-11-12

Circulation (publié)

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

Michael Huang

2024-10-25

bioRxiv (prépublication)

ConvNTC: Convolutional neural tensor completion for predicting the disease-related miRNA pairs and cell-related drug pairs

Pei Liu

Xiao Liang

Jiawei Luo

2024-10-24

bioRxiv (prépublication)

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

Ruohan Wang

Zilong Wang

Ziyang Song

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.

2024-10-17

ArXiv (prépublication)

arxiv.org

Cell ontology guided transcriptome foundation model

Xinyu Yuan

Zhihao Zhan

Zuobai Zhang

Manqi Zhou

Jianan Zhao

Boyu Han

Jian Tang

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.

2024-10-11

NeurIPS.cc/2024/Workshop/FM4Science (poster)

TrajGPT: Healthcare Time-Series Representation Learning for Trajectory Prediction

Ziyang Song

Qincheng Lu

Mike He Zhu

In many domains, such as healthcare, time-series data is irregularly sampled with varying intervals between observations. This creates chall… (voir plus)enges for classical time-series models that require equally spaced data. To address this, we propose a novel time-series Transformer called **Trajectory Generative Pre-trained Transformer (TrajGPT)**. It introduces a data-dependent decay mechanism that adaptively forgets irrelevant information based on clinical context. By interpreting TrajGPT as ordinary differential equations (ODEs), our approach captures continuous dynamics from sparse and irregular time-series data. Experimental results show that TrajGPT, with its time-specific inference approach, accurately predicts trajectories without requiring task-specific fine-tuning.

2024-10-10

NeurIPS.cc/2024/Workshop/TSALM (publié)

TrajGPT: Healthcare Time-Series Representation Learning for Trajectory Prediction

Ziyang Song

Qincheng Lu

Mike He Zhu

2024-10-10

NeurIPS.cc/2024/Workshop/TSALM (publié)

TrajGPT: Irregular Time-Series Representation Learning for Health Trajectory Analysis

Ziyang Song

Qingcheng Lu

He Zhu

2024-10-03

ArXiv (prépublication)

arxiv.org

Cell ontology guided transcriptome foundation model

Xinyu Yuan

Zhihao Zhan

Zuobai Zhang

Manqi Zhou

Jianan Zhao

Boyu Han

Jian Tang

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.

2024-09-25

NeurIPS.cc/2024/Conference (spotlight)