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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn.

Anna-Maria Liebhoff1,2, Thiagarajan Venkataraman2, William R Morgenlander2

  • 1Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.

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|August 14, 2023
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Summary

Researchers profiled antibody responses to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). A new method, Dolphyn, significantly improved PhIP-Seq efficiency and revealed immune responses to bacteria-infecting viruses in the gut.

Keywords:
PhIP-Seqantibody profilinggut phagespeptides librariespublic epitopes

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Area of Science:

  • Immunology
  • Microbiology
  • Bioinformatics

Background:

  • The gut-immune axis is crucial for health, but the antibody response to gut phages remains underexplored.
  • Phage Immunoprecipitation Sequencing (PhIP-Seq) is a method to profile antibody responses to phages.
  • Existing PhIP-Seq methods have limitations in library size and efficiency.

Approach:

  • Developed Dolphyn, a novel machine learning method to select optimal peptides for PhIP-Seq libraries.
  • Dolphyn utilizes epitope-stitching to compress proteomes, reducing the number of synthesized peptides.
  • Applied Dolphyn-enhanced PhIP-Seq to profile antibody responses to gut phages in healthy individuals.

Key Points:

  • Dolphyn improved the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals.
  • Dolphyn reduced the number of synthesized peptides by 78%, making PhIP-Seq more cost-effective.
  • Identified significant antibody responses to bacteria-infecting viruses, particularly E. coli-infecting Myoviridae, in the human gut.

Conclusions:

  • Dolphyn significantly enhances the efficiency and cost-effectiveness of PhIP-Seq for studying gut phages.
  • The human immune system actively targets bacteria-infecting viruses within the gut microbiome.
  • This approach facilitates broader investigation of the gut-immune axis and phage-host interactions.