IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-49806-9.html
   My bibliography  Save this article

Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data

Author

Listed:
  • Felix Drost

    (Helmholtz Munich
    Technical University of Munich)

  • Yang An

    (Helmholtz Munich
    Technical University of Munich)

  • Irene Bonafonte-Pardàs

    (Helmholtz Munich)

  • Lisa M. Dratva

    (Wellcome Genome Campus)

  • Rik G. H. Lindeboom

    (The Netherlands Cancer Institute)

  • Muzlifah Haniffa

    (Wellcome Genome Campus
    Newcastle University)

  • Sarah A. Teichmann

    (Wellcome Genome Campus
    University of Cambridge)

  • Fabian Theis

    (Helmholtz Munich
    Technical University of Munich
    Technical University of Munich)

  • Mohammad Lotfollahi

    (Helmholtz Munich
    Wellcome Genome Campus)

  • Benjamin Schubert

    (Helmholtz Munich
    Technical University of Munich)

Abstract

Recent advances in single-cell immune profiling have enabled the simultaneous measurement of transcriptome and T cell receptor (TCR) sequences, offering great potential for studying immune responses at the cellular level. However, integrating these diverse modalities across datasets is challenging due to their unique data characteristics and technical variations. Here, to address this, we develop the multimodal generative model mvTCR to fuse modality-specific information across transcriptome and TCR into a shared representation. Our analysis demonstrates the added value of multimodal over unimodal approaches to capture antigen specificity. Notably, we use mvTCR to distinguish T cell subpopulations binding to SARS-CoV-2 antigens from bystander cells. Furthermore, when combined with reference mapping approaches, mvTCR can map newly generated datasets to extensive T cell references, facilitating knowledge transfer. In summary, we envision mvTCR to enable a scalable analysis of multimodal immune profiling data and advance our understanding of immune responses.

Suggested Citation

  • Felix Drost & Yang An & Irene Bonafonte-Pardàs & Lisa M. Dratva & Rik G. H. Lindeboom & Muzlifah Haniffa & Sarah A. Teichmann & Fabian Theis & Mohammad Lotfollahi & Benjamin Schubert, 2024. "Multi-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49806-9
    DOI: 10.1038/s41467-024-49806-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-49806-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-49806-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Yingxia Zheng & Zheyi Chen & Yichao Han & Li Han & Xin Zou & Bingqian Zhou & Rui Hu & Jie Hao & Shihao Bai & Haibo Xiao & Wei Vivian Li & Alex Bueker & Yanhui Ma & Guohua Xie & Junyao Yang & Shiyu Che, 2020. "Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. David S. Fischer & Meshal Ansari & Karolin I. Wagner & Sebastian Jarosch & Yiqi Huang & Christoph H. Mayr & Maximilian Strunz & Niklas J. Lang & Elvira D’Ippolito & Monika Hammel & Laura Mateyka & Sim, 2021. "Single-cell RNA sequencing reveals ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse phenotyping’," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Justina X. Caushi & Jiajia Zhang & Zhicheng Ji & Ajay Vaghasia & Boyang Zhang & Emily Han-Chung Hsiue & Brian J. Mog & Wenpin Hou & Sune Justesen & Richard Blosser & Ada Tam & Valsamo Anagnostou & Tri, 2021. "Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers," Nature, Nature, vol. 596(7870), pages 126-132, August.
    4. Peter A. Szabo & Hanna Mendes Levitin & Michelle Miron & Mark E. Snyder & Takashi Senda & Jinzhou Yuan & Yim Ling Cheng & Erin C. Bush & Pranay Dogra & Puspa Thapa & Donna L. Farber & Peter A. Sims, 2019. "Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    5. April R. Kriebel & Joshua D. Welch, 2022. "UINMF performs mosaic integration of single-cell multi-omic datasets using nonnegative matrix factorization," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Justina X. Caushi & Jiajia Zhang & Zhicheng Ji & Ajay Vaghasia & Boyang Zhang & Emily Han-Chung Hsiue & Brian J. Mog & Wenpin Hou & Sune Justesen & Richard Blosser & Ada Tam & Valsamo Anagnostou & Tri, 2021. "Author Correction: Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers," Nature, Nature, vol. 598(7881), pages 1-1, October.
    7. John-William Sidhom & H. Benjamin Larman & Drew M. Pardoll & Alexander S. Baras, 2021. "DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    8. Pradyot Dash & Andrew J. Fiore-Gartland & Tomer Hertz & George C. Wang & Shalini Sharma & Aisha Souquette & Jeremy Chase Crawford & E. Bridie Clemens & Thi H. O. Nguyen & Katherine Kedzierska & Nicole, 2017. "Quantifiable predictive features define epitope-specific T cell receptor repertoires," Nature, Nature, vol. 547(7661), pages 89-93, July.
    9. John-William Sidhom & H. Benjamin Larman & Drew M. Pardoll & Alexander S. Baras, 2021. "Author Correction: DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires," Nature Communications, Nature, vol. 12(1), pages 1-1, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Elliot H. Akama-Garren & Theo Broek & Lea Simoni & Carlos Castrillon & Cees E. Poel & Michael C. Carroll, 2021. "Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    2. Olivia Le Saux & Maude Ardin & Justine Berthet & Sarah Barrin & Morgane Bourhis & Justine Cinier & Yasmine Lounici & Isabelle Treilleux & Pierre-Alexandre Just & Guillaume Bataillon & Aude-Marie Savoy, 2024. "Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Wolfgang Beckabir & Mi Zhou & Jin Seok Lee & Steven P. Vensko & Mark G. Woodcock & Hsing-Hui Wang & Sara E. Wobker & Gatphan Atassi & Alec D. Wilkinson & Kenneth Fowler & Leah M. Flick & Jeffrey S. Da, 2024. "Immune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Celina Tretter & Niklas Andrade Krätzig & Matteo Pecoraro & Sebastian Lange & Philipp Seifert & Clara Frankenberg & Johannes Untch & Gabriela Zuleger & Mathias Wilhelm & Daniel P. Zolg & Florian S. Dr, 2023. "Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    5. Giancarlo Croce & Sara Bobisse & Dana Léa Moreno & Julien Schmidt & Philippe Guillame & Alexandre Harari & David Gfeller, 2024. "Deep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Ivy K Brown & Nathan Dyjack & Mindy M Miller & Harsha Krovi & Cydney Rios & Rachel Woolaver & Laura Harmacek & Ting-Hui Tu & Brian P O’Connor & Thomas Danhorn & Brian Vestal & Laurent Gapin & Clemenci, 2021. "Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire," PLOS Pathogens, Public Library of Science, vol. 17(6), pages 1-34, June.
    7. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Jing Hu & Mingyao Pan & Brett Reid & Shelley Tworoger & Bo Li, 2024. "Quantifiable blood TCR repertoire components associate with immune aging," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Augusto Faria Andrade & Alva Annett & Elham Karimi & Danai Georgia Topouza & Morteza Rezanejad & Yitong Liu & Michael McNicholas & Eduardo G. Gonzalez Santiago & Dhana Llivichuzhca-Loja & Arne Gehlhaa, 2024. "Immune landscape of oncohistone-mutant gliomas reveals diverse myeloid populations and tumor-promoting function," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    11. Yuyao Song & Zhichao Miao & Alvis Brazma & Irene Papatheodorou, 2023. "Benchmarking strategies for cross-species integration of single-cell RNA sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Ziqi Zhang & Haoran Sun & Ragunathan Mariappan & Xi Chen & Xinyu Chen & Mika S. Jain & Mirjana Efremova & Sarah A. Teichmann & Vaibhav Rajan & Xiuwei Zhang, 2023. "scMoMaT jointly performs single cell mosaic integration and multi-modal bio-marker detection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Estelle Marrer-Berger & Annalisa Nicastri & Angelique Augustin & Vesna Kramar & Hanqing Liao & Lydia Jasmin Hanisch & Alejandro Carpy & Tina Weinzierl & Evelyne Durr & Nathalie Schaub & Ramona Nudisch, 2024. "The physiological interactome of TCR-like antibody therapeutics in human tissues," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    14. Osama Al-Dalahmah & Michael G. Argenziano & Adithya Kannan & Aayushi Mahajan & Julia Furnari & Fahad Paryani & Deborah Boyett & Akshay Save & Nelson Humala & Fatima Khan & Juncheng Li & Hong Lu & Yu S, 2023. "Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Nader Atlasy & Anna Bujko & Espen S. Bækkevold & Peter Brazda & Eva Janssen-Megens & Knut E. A. Lundin & Jørgen Jahnsen & Frode L. Jahnsen & Hendrik G. Stunnenberg, 2022. "Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    16. Xuejiao Liu & Simin Zhao & Keke Wang & Liting Zhou & Ming Jiang & Yunfeng Gao & Ran Yang & Shiwen Yan & Wen Zhang & Bingbing Lu & Feifei Liu & Ran Zhao & Wenting Liu & Zihan Zhang & Kangdong Liu & Xia, 2023. "Spatial transcriptomics analysis of esophageal squamous precancerous lesions and their progression to esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    17. De-Chen Lin, 2023. "Large-scale genomic analyses reveal alterations and mechanisms underlying clonal evolution and immune evasion in esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-3, December.
    18. Qi Zhang & Rober Abdo & Cristiana Iosef & Tomonori Kaneko & Matthew Cecchini & Victor K. Han & Shawn Shun-Cheng Li, 2022. "The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    19. Alexandra Argyriou & Marc H. Wadsworth & Adrian Lendvai & Stephen M. Christensen & Aase H. Hensvold & Christina Gerstner & Annika Vollenhoven & Kellie Kravarik & Aaron Winkler & Vivianne Malmström & K, 2022. "Single cell sequencing identifies clonally expanded synovial CD4+ TPH cells expressing GPR56 in rheumatoid arthritis," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    20. Anja Fischer & Thomas K. Albert & Natalia Moreno & Marta Interlandi & Jana Mormann & Selina Glaser & Paurnima Patil & Flavia W. Faria & Mathis Richter & Archana Verma & Sebastian T. Balbach & Rabea Wa, 2024. "Lack of SMARCB1 expression characterizes a subset of human and murine peripheral T-cell lymphomas," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49806-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.