Integration of imaging-based and sequencing-based spatial omics mapping on the same tissue section via DBiTplus
Year: 2026
Type: article
Abstract: Spatially mapping the transcriptome and proteome in the same tissue section can profoundly advance our understanding of cellular heterogeneity and function. Here we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multimodal spatial omics approach combining sequencing-based spatial transcriptomics and multiplexed protein imaging on the same section, enabling both single-cell-resolution cell typing and transcriptome-wide interrogation of biological pathways. DBiTplus utilizes spatial barcoding and RNase H-mediated cDNA retrieval, preserving tissue architecture for multiplexed protein imaging. We developed computational pipelines to integrate these modalities, allowing imaging-guided deconvolution to generate single-cell-resolved spatial transcriptome atlases. We demonstrate DBiTplus across diverse samples including frozen mouse embryos, and formalin-fixed paraffin-embedded human lymph nodes and lymphoma tissues, highlighting its compatibility with challenging clinical specimens. DBiTplus uncovered mechanisms of lymphomagenesis, progression and transformation in human lymphomas. Thus, DBiTplus is a unified workflow for spatially resolved single-cell atlasing and unbiased exploration of biological mechanisms in a cell-by-cell manner at transcriptome scale.
Source: Nature Methods
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Science Foundation, Yale University, Center for Selective C-H Functionalization, National Science Foundation, National Institutes of Health, National Institute on Aging, National Institute of Mental Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases
Awards: DMS/NIGMS 1: Statistical Methods for Design and Analysis of Clinical-scale Single Cell Studies, High-spatial-resolution ECM-inclusive multi-omics sequencing of human PFA and FFPE tissue slides, High-spatial-resolution ECM-inclusive multi-omics sequencing of human PFA and FFPE tissue slides, Center for Human Lymphoma Spatiotemporal Atlas (HuLymSTA), Ex vivo analysis of human brain tumor cells in a microvascular niche model, G8154313960, Matching and Data Integration, Highly scalable and sensitive spatial transcriptomic and epigenomic sequencing of brain tissues from human and non-human primate, Yale TMC for Cellular Senescence in Lymphoid Organs, Center for 3D Imaging in Cancer Cell Biology, Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics), High-throughput in vivo and in vitro functional and multi-omics screens of neuropsychiatric and neurodevelopmental disorder risk genes, Immune signatures of vaccine responses in vulnerable populations, Yale Murine-TMC on Immune Cell Senescence Derived Inflammation
OpenAlex ID: W7124299183