Work

Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn

Year: 2024

Type: article

Abstract: We investigate a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To cover large antigenic spaces, we develop Dolphyn, a method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn compresses the size of a peptide library by 78% compared to traditional tiling, increasing the antibody-reactive peptides from 10% to 31%. We find that the immune system develops antibodies to human gut bacteria-infecting viruses, particularly E.coli-infecting Myoviridae. Cost-effective PhIP-Seq libraries designed with Dolphyn enable the assessment of a wider range of proteins in a single experiment, thus facilitating the study of the gut-immune axis.

Source: Nature Communications

DOI: 10.1038/s41467-024-45601-8

Authors: Anna-Maria Liebhoff, Thiagarajan Venkataraman, William R. Morgenlander, Miso Na, Tomasz Kula, Kathleen Waugh, Charles Morrison, Marian Rewers, Randy Longman, June Round, Stephen Elledge, Ingo Ruczinski, Ben Langmead, H. Benjamin Larman

Institutions: Johns Hopkins University, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard University, University of Colorado Denver, Family Health International 360, Weill Cornell Medicine, University of Utah

Language: English

Topic: vaccines and immunoinformatics approaches

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,790

Funders: Howard Hughes Medical Institute, Leona M. and Harry B. Helmsley Charitable Trust, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: Design and Analysis of Displayed Peptidomes, Natural History of Pre-Diabetic Autoimmunity (DAISY), Natural History of Pre-diabetic Autoimmunity (DAISY), G9000160037, University of Colorado Anschutz Medical Campus DRC, LC: HIV PREVENTION TRIALS NETWORK, Medical Scientist Training Program, Methods for sequencing data analysis and archive-scale data science

OpenAlex ID: W4391998003

FWCI: 1.446

Cites: 29

Cited by: 13

Related to: 10