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Related Concept Videos

Imaging Biological Samples with Optical Microscopy01:18

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Optical microscopy uses optic principles to provide detailed images of samples. Antonie van Leeuwenhoek designed the first compound optical microscope in the 17th century to visualize blood cells, bacteria, and yeast cells. In 1830, Joseph Jackson Lister created an essentially modern light microscope. The 20th century saw the development of microscopes with enhanced magnification and resolution.
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Related Experiment Video

Updated: Jan 17, 2026

Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
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Integration of imaging-based and sequencing-based spatial omics mapping on the same tissue section via DBiTplus.

Archibald Enninful1, Zhaojun Zhang2, Dmytro Klymyshyn3

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

Nature Methods
|January 15, 2026
PubMed
Summary
This summary is machine-generated.

Deterministic Barcoding in Tissue sequencing plus (DBiTplus) integrates spatial transcriptomics and protein imaging. This multimodal approach maps cells and pathways in tissues, advancing understanding of cellular heterogeneity and disease mechanisms.

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Area of Science:

  • Spatial Omics
  • Molecular Biology
  • Bioinformatics

Background:

  • Understanding cellular heterogeneity and function requires mapping molecular data within tissue architecture.
  • Current spatial omics methods often lack multi-modal integration or single-cell resolution.

Purpose of the Study:

  • To present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multimodal spatial omics approach.
  • To enable simultaneous spatial transcriptomics and multiplexed protein imaging on the same tissue section.
  • To generate single-cell-resolved spatial transcriptome atlases and explore biological pathways.

Main Methods:

  • DBiTplus combines sequencing-based spatial transcriptomics with multiplexed protein imaging.
  • Utilizes spatial barcoding and RNase H-mediated cDNA retrieval to preserve tissue for protein analysis.
  • Employs computational pipelines for integrating multi-omics data and imaging-guided deconvolution.

Main Results:

  • DBiTplus successfully maps transcriptome and proteome at single-cell resolution on the same tissue section.
  • Demonstrated compatibility with diverse samples, including challenging formalin-fixed paraffin-embedded clinical specimens.
  • Uncovered mechanisms of lymphomagenesis, progression, and transformation in human lymphomas.

Conclusions:

  • DBiTplus is a unified workflow for spatially resolved single-cell atlasing.
  • Enables unbiased, cell-by-cell exploration of biological mechanisms at the transcriptome scale.
  • Advances understanding of cellular heterogeneity and function in various biological contexts.