biostudies-literatureDrost FBundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)Deutsche Forschungsgemeinschaft (German Research Foundation)5577https://www.ebi.ac.uk/biostudies/studies/S-EPMC11220149biostudies-literatureUnknown15(1)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 referencNature communicationsMulti-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data.PMC11220149490846870#031L0290AHaniffa MTheis FDratva LMLindeboom RGHAn YDrost FLotfollahi MSchubert BBonafonte-Pardas ITeichmann SAfalseMulti-modal generative modeling for joint analysis of single-cell T cell receptor and gene expression data.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 referenc2024-01-01T00:00:00Z2024 Jul2025-04-04T12:54:38.644Z2025-04-04T12:54:38.644ZS-EPMC112201493895608210.1038/s41467-024-49806-9