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A new method, phage-antibody next-generation sequencing (PhaNGS), profiles cell surface proteins. This technique aids in classifying cell states and understanding diseases like leukemia.

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Area of Science:

  • Proteomics
  • Immunology
  • Genomics

Background:

  • Human cells have thousands of surface proteins crucial for cell classification and disease identification.
  • Current methods for profiling surface proteins are often limited in scope and cost-effectiveness.

Purpose of the Study:

  • To develop a highly multiplexed and quantitative method for simultaneous surface proteome profiling.
  • To enable more accurate and complete classification of cell states.

Main Methods:

  • Phage-antibody next-generation sequencing (PhaNGS) utilizes genetically barcoded antibodies displayed on phage.
  • 144 preselected antibodies targeting 44 receptor targets were employed.
  • The method was applied to B cells from acute lymphoblastic leukemia (ALL) patients and a Burkitt lymphoma model.

Main Results:

  • PhaNGS successfully assessed changes in B cell surface proteins during drug resistance and oncogene adaptation.
  • Common proteins like FLT3, NCR3LG1, and ROR1 were identified as key responders to oncogenic perturbations.
  • The technique demonstrated applicability at the single-cell level.

Conclusions:

  • PhaNGS offers a direct, highly multiplexed, and cost-effective approach for surface protein detection.
  • This method has the potential to significantly advance cell state classification and disease research.
  • PhaNGS provides protein detection comparable in scope to RNA-sequencing for mRNA.