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Related Experiment Video

Updated: Oct 7, 2025

Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
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Spatial transcriptomics using combinatorial fluorescence spectral and lifetime encoding, imaging and analysis.

Tam Vu1,2, Alexander Vallmitjana1,3, Joshua Gu2,4

  • 1Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, 92697, USA.

Nature Communications
|January 11, 2022
PubMed
Summary
This summary is machine-generated.

We developed a new spatialomics technology, MOSAICA, for multiplexed mRNA and protein profiling. This advanced method enhances spatial transcriptomics, offering scalable and accurate analysis for cancer research.

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cancer Research

Background:

  • Spatial transcriptomics offers novel insights for research and clinical applications.
  • Existing methods face limitations in multiplexing capability and complexity.
  • Accurate spatial profiling of multiple targets is crucial for understanding cellular heterogeneity.

Purpose of the Study:

  • To introduce a novel spatialomics technology, MOSAICA (Multi Omic Single-scan Assay with Integrated Combinatorial Analysis).
  • To demonstrate the scalability and accuracy of MOSAICA for multiplexed mRNA and protein detection.
  • To validate MOSAICA's performance against established techniques and in clinical samples.

Main Methods:

  • MOSAICA integrates in situ labeling of mRNA and protein markers using combinatorial fluorescence spectral and lifetime encoded probes.
  • Spectral and time-resolved fluorescence imaging combined with machine learning-based decoding enables high-plex analysis.
  • Error detection and autofluorescence removal were implemented for robust data acquisition.

Main Results:

  • MOSAICA achieved 10-plex target detection in colorectal cancer cells with high accuracy.
  • Analysis showed strong correlation with sequencing data (Pearson's r = 0.96) and was benchmarked against RNAscope and LGC Stellaris.
  • The technology was successfully applied to clinical melanoma Formalin-Fixed Paraffin-Embedded (FFPE) tissues, demonstrating simultaneous protein and mRNA co-detection.

Conclusions:

  • MOSAICA represents a scalable and robust spatialomics technology for multiplexed mRNA and protein profiling.
  • The method overcomes limitations of existing spatial transcriptomics techniques, offering improved multiplexing and reduced complexity.
  • MOSAICA holds significant potential for advancing basic research and clinical diagnostics in oncology and beyond.