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Updated: Nov 30, 2025

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High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue.

Yang Liu1, Mingyu Yang1, Yanxiang Deng1

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA.

Cell
|November 14, 2020
PubMed
Summary
This summary is machine-generated.

Deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) enables simultaneous mapping of mRNA and proteins in fixed tissues. This technique provides high-resolution spatial omics data for diverse biological research applications.

Keywords:
high spatial resolutionin situ barcodingmouse embryonext-generation sequencingspatial multi-omics

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Area of Science:

  • Spatial Omics
  • Molecular Biology
  • Genomics

Background:

  • Spatial omics technologies are crucial for understanding tissue architecture and cellular heterogeneity.
  • Simultaneous mapping of multiple biomolecules (e.g., mRNA and proteins) at high resolution remains a challenge.

Purpose of the Study:

  • To develop a novel method, deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq), for co-mapping mRNAs and proteins in fixed tissue slides.
  • To enable high-resolution spatial transcriptomics and proteomics using next-generation sequencing (NGS).

Main Methods:

  • DBiT-seq utilizes parallel microfluidic channels to deliver DNA barcodes to a tissue slide surface.
  • Sequential delivery and in situ ligation of two barcode sets (A and B) create unique 2D barcodes for each tissue pixel.
  • Next-generation sequencing (NGS) is employed for readout of the spatial omics data.

Main Results:

  • DBiT-seq successfully co-mapped mRNAs and proteins in formaldehyde-fixed mouse embryo tissues.
  • High-resolution mapping revealed major tissue types during organogenesis and fine structures like microvasculature and pigmented epithelium.
  • Gene expression profiles from 10-μm pixels clustered with single-cell transcriptomes, enabling rapid cell type and spatial distribution identification.

Conclusions:

  • DBiT-seq offers a user-friendly approach for spatial omics, accessible to researchers without microfluidics expertise.
  • This technique has broad applications in developmental biology, cancer biology, neuroscience, and clinical pathology.
  • DBiT-seq advances the field of spatial biology by enabling integrated multi-omics analysis in situ.