Yue Li

Claris Gu

Maîtrise recherche - McGill

Eric Huang

Maîtrise recherche - 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

Doctorat - McGill

Co-superviseur⋅e :

Jun Ding

Jack Song

Maîtrise recherche - McGill

Co-superviseur⋅e :

Archer Yang

Bo-Hong Wang

Maîtrise recherche - McGill

Kunpeng Xu

Postdoctorat - McGill

Co-superviseur⋅e :

Archer Yang

Publications

PheCode-guided multi-modal topic modeling of electronic health records improves disease incidence prediction and GWAS discovery from UK Biobank

Ziqi Yang

Ziyang Song

Shadi Zabad

Marc-André Legault

Phenome-wide association studies rely on disease definitions derived from diagnostic codes, often failing to leverage the full richness of e… (voir plus)lectronic health records (EHR). We present MixEHR-SAGE, a PheCode-guided multi-modal topic model that integrates diagnoses, procedures, and medications to enhance phenotyping from large-scale EHRs. By combining expert-informed priors with probabilistic inference, MixEHR-SAGE identifies over 1000 interpretable phenotype topics from UK Biobank data. Applied to 350 000 individuals with high-quality genetic data, MixEHR-SAGE-derived risk scores accurately predict incident type 2 diabetes (T2D) and leukemia diagnoses. Subsequent genome-wide association studies using these continuous risk scores uncovered novel disease-associated loci, including PPP1R15A for T2D and JMJD6/SRSF2 for leukemia, that were missed by traditional binary case definitions. These results highlight the potential of probabilistic phenotyping from multi-modal EHRs to improve genetic discovery. The MixEHR-SAGE software is publicly available at: https://github.com/li-lab-mcgill/MixEHR-SAGE.

2025-12-31

Briefings in Bioinformatics (publié)

SpaTM: Topic Models for Inferring Spatially Informed Transcriptional Programs

Adrien Osakwe

Wenqi Dong

Qihuang Zhang

Robert Sladek

Spatial transcriptomics has revolutionized our ability to characterize tissues and diseases by contextualizing gene expression with spatial … (voir plus)organization. Available methods require researchers to either train a model using histology-based annotations or use annotation-free clustering approaches to uncover spatial domains. However, few methods provide researchers with a way to jointly analyze spatial data from both annotation-free and annotation-guided perspectives using consistent inductive biases and levels of interpretability. A single framework with consistent inductive biases ensures coherence and transferability across tasks, reducing the risks of conflicting assumptions. To this end, we propose the Spatial Topic Model (SpaTM), a topic-modeling framework capable of annotation-guided and annotation-free analysis of spatial transcriptomics data. SpaTM can be used to learn gene programs that represent histology-based annotations while providing researchers with the ability to infer spatial domains with an annotation-free approach if manual annotations are limited or noisy. We demonstrate SpaTM’s interpretability with its use of topic mixtures to represent cell states and transcriptional programs and how its intuitive framework facilitates the integration of annotation-guided and annotation-free analyses of spatial data with downstream analyses such as cell type deconvolution. Finally, we demonstrate how both approaches can be used to extend the analysis of large-scale snRNA-seq atlases with the inference of cell proximity and spatial annotations in human brains with Major Depressive Disorder.

2025-12-07

Briefings in Bioinformatics (publié)

MiRformer: a dual-transformer-encoder framework for predicting microRNA-mRNA interactions from paired sequences

Jiayao Gu

Can (Sam) Chen

MicroRNAs (miRNAs) are small non-coding RNAs that regulate genes by binding to target messenger RNAs (mRNAs), causing them to degrade or sup… (voir plus)pressing their translation. Accurate prediction of miRNA–mRNA interactions is crucial for RNA therapeutics. Existing methods rely on handcrafted features, struggle to scale to kilobase-long mRNA sequences, or lack interpretability. We introduce MiRformer , a transformer framework designed to predict not only the binary miRNA–mRNA interaction but also the start and end location of the miRNA binding site in the mRNA sequence. MiRformer employs a dual-transformer encoder architecture to learn interaction patterns directly from raw miRNA-mRNA sequence pairs via the cross-attention between the miRNA-encoder and mRNA-encoder. To scale to long mRNA sequences, we leverage sliding-window attention mechanism. MiR-former achieves state-of-the-art performance across diverse miRNA–mRNA tasks, including binding prediction, target-site localization, and cleavage-site identification from Degradome sequencing data. The learned transformer attention are highly interpretable and reveals highly contrasting signals for the miRNA seed regions in 500-nt long mRNA sequences. We used MiRformer to simultaneously predict novel binding sites and cleavage sites in 13k miRNA-mRNA pairs and observed that the two types of sites tend to be close to each other, supporting miRNA-mediated degradation mechanism. Our code is available at https://github.com/li-lab-mcgill/miRformer .

2025-11-23

bioRxiv (prépublication)

TimelyGPT: Extrapolatable Transformer Pre-training for Long-term Time-Series Forecasting in Healthcare

Ziyang Song

Qincheng Lu

Hao Xu

Ziqi Yang

Mike He Zhu

Motivation: Large-scale pre-trained models (PTMs) such as BERT and GPT have recently achieved great success in Natural Language Processing a… (voir plus)nd Computer Vision domains. However, the development of PTMs on healthcare time-series data is lagging behind. This underscores the limitations of the existing transformer-based architectures, particularly their scalability to handle large-scale time series and ability to capture long-term temporal dependencies. Methods: In this study, we present Timely Generative Pre-trained Transformer (TimelyGPT). TimelyGPT employs an extrapolatable position (xPos) embedding to encode trend and periodic patterns into time-series representations. It also integrates recurrent attention and temporal convolution modules to effectively capture global-local temporal dependencies. Materials: We evaluated TimelyGPT on two large-scale healthcare time series datasets corresponding to continuous biosignals and irregularly-sampled time series, respectively: (1) the Sleep EDF dataset consisting of over 1.2 billion timesteps; (2) the longitudinal healthcare administrative database PopHR, comprising 489,000 patients randomly sampled from the Montreal population. Results: In forecasting continuous biosignals, TimelyGPT achieves accurate extrapolation up to 6,000 timesteps of body temperature during the sleep stage transition, given a short look-up window (i.e., prompt) containing only 2,000 timesteps. For irregularly-sampled time series, TimelyGPT with a proposed time-specific inference demonstrates high top recall scores in predicting future diagnoses using early diagnostic records, effectively handling irregular intervals between clinical records. Together, we envision TimelyGPT to be useful in various health domains, including long-term patient health state forecasting and patient risk trajectory prediction. Availability: The open-sourced code is available at Github.

2025-10-14

Health Information Science and Systems (publié)

arxiv.org

Timelygpt: extrapolatable transformer pre-training for long-term time-series forecasting in healthcare

Ziyang Song

Qincheng Lu

Hao Xu

Ziqi Yang

Mike He Zhu

2025-10-14

Health Information Science and Systems (publié)

www.ncbi.nlm.nih.gov

TrajGPT: Irregular Time-Series Representation Learning of Health Trajectory.

Ziyang Song

Qincheng Lu

Mike He Zhu

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.

2025-10-13

IEEE journal of biomedical and health informatics (publié)

TrajGPT: Irregular Time-Series Representation Learning of Health Trajectory.

Ziyang Song

Qincheng Lu

Mike He Zhu

2025-10-13

IEEE journal of biomedical and health informatics (publié)