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Dylan Mann-Krzisnik

PhD - McGill University
Supervisor
Yue Li
Research Topics
Computational Biology
Multimodal Learning

Publications

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
Yue Li
Integrating multimodal single-cell data such as scRNA-seq with scATAC-seq is essential for decoding gene regulatory networks, but remains di… (see more)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 (preprint)
doi.org
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
Yue Li
2024-05-31
STAR Protocols (published)
doi.org
Single-cell multi-omic topic embedding reveals cell-type-specific and COVID-19 severity-related immune signatures
Manqi Zhou
Hao Zhang
Zilong Bai
Dylan Mann-Krzisnik
Fei Wang
Yue Li
The advent of single-cell multi-omics sequencing technology makes it possible for re-searchers to leverage multiple modalities for individua… (see more)l cells and explore cell heterogeneity. However, the high dimensional, discrete, and sparse nature of the data make the downstream analysis particularly challenging. Most of the existing computational methods for single-cell data analysis are either limited to single modality or lack flexibility and interpretability. In this study, we propose an interpretable deep learning method called multi-omic embedded topic model (moETM) to effectively perform integrative analysis of high-dimensional single-cell multimodal data. moETM integrates multiple omics data via a product-of-experts in the encoder for efficient variational inference and then employs multiple linear decoders to learn the multi-omic signatures of the gene regulatory programs. Through comprehensive experiments on public single-cell transcriptome and chromatin accessibility data (i.e., scRNA+scATAC), as well as scRNA and proteomic data (i.e., CITE-seq), moETM demonstrates superior performance compared with six state-of-the-art single-cell data analysis methods on seven publicly available datasets. By applying moETM to the scRNA+scATAC data in human bone marrow mononuclear cells (BMMCs), we identified sequence motifs corresponding to the transcription factors that regulate immune gene signatures. Applying moETM analysis to CITE-seq data from the COVID-19 patients revealed not only known immune cell-type-specific signatures but also composite multi-omic biomarkers of critical conditions due to COVID-19, thus providing insights from both biological and clinical perspectives.
2023-01-30
bioRxiv (preprint)
doi.org