# PhIP-Seq: unveiling the complexity of antibody repertoires in health and disease

## TL;DR

PhIP-Seq is a powerful method combining phage display and sequencing to study antibody repertoires, with applications in understanding diseases like lupus and tracking viral epitopes.

## Contribution

This paper reviews the technical evolution and clinical applications of PhIP-Seq, highlighting its potential in autoimmunity and infectious disease research.

## Key findings

- PhIP-Seq enables high-throughput profiling of antibody repertoires by combining phage display and next-generation sequencing.
- The method has been used to identify novel autoantigens in systemic lupus erythematosus and multiple sclerosis.
- PhIP-Seq is being integrated with multi-omics datasets and advancing toward point-of-care diagnostics.

## Abstract

Phage-Immunoprecipitation Sequencing (PhIP-Seq) merges phage display with next-generation sequencing to enable high-throughput profiling of antibody repertoires. This review synthesizes the technical evolution of the PhIP-Seq platform, critically assessing the workflow from peptide library design and immunoprecipitation to bioinformatics analysis. We evaluate strategies for optimizing library diversity and minimizing non-specific binding, while addressing inherent limitations such as the detection of conformational epitopes and post-translational modifications. The clinical utility of PhIP-Seq is examined through its application in identifying novel autoantigens in systemic lupus erythematosus and multiple sclerosis, mapping viral epitopes in SARS-CoV-2 and Plasmodium falciparum, and detecting tumor-associated antigens. Finally, we discuss the trajectory of the field toward integration with multi-omics datasets and the development of point-of-care diagnostic tools.