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Related Experiment Video

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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, 06520, USA.

Biorxiv : the Preprint Server for Biology
|November 28, 2024
PubMed
Summary

Deterministic Barcoding in Tissue sequencing plus (DBiTplus) integrates spatial transcriptomics and protein profiling. This spatial omics approach enables single-cell resolution cell typing and genome-scale pathway analysis on the same tissue section.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Biotechnology

Background:

  • Understanding cellular heterogeneity and function requires simultaneous analysis of both transcriptomic and proteomic data within intact tissue sections.
  • Current spatial omics technologies often analyze these modalities separately, limiting comprehensive cellular profiling.

Purpose of the Study:

  • To introduce Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multi-modal spatial omics platform.
  • To enable single-cell resolution cell typing and genome-scale biological pathway interrogation on the same tissue section.

Main Methods:

  • DBiTplus combines sequencing-based spatial transcriptomics with image-based spatial protein profiling (CODEX) on identical tissue sections.
  • The workflow involves *in situ* reverse transcription, microfluidic spatial barcoding, RNaseH-mediated cDNA retrieval, and high-plex protein imaging.
  • Computational pipelines were developed for accurate multi-modal data registration and integration.

Main Results:

  • DBiTplus successfully generated single-cell resolved spatial transcriptome atlases by integrating transcriptomic and proteomic data.
  • The approach demonstrated accurate cell typing and enabled image-guided decomposition for transcriptome analysis.
  • Applications in mouse embryos, human lymph nodes, and human lymphoma FFPE tissues showcased its versatility and power for biological discovery.

Conclusions:

  • DBiTplusCODEX provides a unified workflow for spatially resolved single-cell atlasing and cell-by-cell exploration of biological pathways at genome scale.
  • This integrative spatial omics approach significantly advances the ability to connect cell type to function in complex biological systems.
  • DBiTplus facilitates deeper understanding of tissue heterogeneity, developmental processes, and disease mechanisms like lymphomagenesis.