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Drost, F. ; An, Y. ; Bonafonte Pardás, I. ; Dratva, L.M.* ; Lindeboom, R.G.H.* ; Haniffa, M.* ; Teichmann, S.A.* ; Theis, F.J. ; Lotfollahi, M. ; Schubert, B.

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

Nat. Commun. 15:5577 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Memory; Effector; Naive; Activation; Prediction; Landscape; Profiles; Reveals
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 5577 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen European Union
Joachim Herz Stiftung
Helmholtz Association
Helmholtz International Lab "Causal Cell Dynamics"
Helmholtz Association's Initiative and Networking Fund on the HAICORE@FZJ partition
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
BMBF grant DeepTCR
Projekt DEAL