High-throughput single-cell quantification of hundreds of proteins using conventional flow cytometry and machine

Etienne Becht1, Daniel Tolstrup2, Charles-Antoine Dutertre3,4,5

  • 1Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Science Advances
|September 22, 2021
PubMed

Insights

Infinity Flow uses machine learning to analyze hundreds of proteins on millions of cells, revealing new insights into lung tissue and cancer. This cost-effective method enhances single-cell proteomics for complex biological systems.

Area of Science:

  • Immunology
  • Proteomics
  • Computational Biology

Background:

  • High-dimensional analysis is crucial for understanding complex disease microenvironments.
  • Current methods face limitations in analyzing vast cellular and protein data.

Purpose of the Study:

  • To develop a scalable and cost-effective method for high-dimensional single-cell proteomics.
  • To comprehensively analyze cellular heterogeneity in complex tissues like the lung.

Main Methods:

  • Developed Infinity Flow, integrating hundreds of flow cytometry panels with machine learning.
  • Applied supervised machine learning to enhance clustering and dimensionality reduction algorithms.
  • Analyzed millions of individual cells for coexpression patterns of hundreds of surface proteins.

Main Results:

  • Enabled comprehensive analysis of steady-state murine lung cellular composition.
  • Identified novel cellular heterogeneity in lungs of mice with melanoma metastasis.
  • Demonstrated enhanced accuracy and depth in data analysis using Infinity Flow.

Conclusions:

  • Infinity Flow provides a scalable, low-cost solution for single-cell proteomics in complex tissues.
  • The approach significantly advances the ability to dissect cellular heterogeneity in disease.
  • Facilitates deeper understanding of tissue microenvironments in immunology research.