Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn

Liebhoff, A.-M.; Venkataraman, T.; Morgenlander, W. R.; Na, M.; Kula, T.; Waugh, K.; Morrison, C.; Rewers, M.; Longman, R.; Round, J.; Elledge, S.; Ruczinski, I.; Langmead, B.; Larman, H. B.

doi:10.1101/2023.07.30.551179

bioRxiv · 10.1101/2023.07.30.551179

Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn

Liebhoff, A.-M.·Venkataraman, T.·Morgenlander, W. R.·Na, M.·Kula, T.·Waugh, K.·Morrison, C.·Rewers, M.·Longman, R.·Round, J.·Elledge, S.·Ruczinski, I.·Langmead, B.·Larman, H. B.

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Abstract

We investigated a relatively underexplored component of the gut-immune axis by profiling the antibody response to gut phages using Phage Immunoprecipitation Sequencing (PhIP-Seq). To enhance this approach, we developed Dolphyn, a novel method that uses machine learning to select peptides from protein sets and compresses the proteome through epitope-stitching. Dolphyn improves the fraction of gut phage library peptides bound by antibodies from 10% to 31% in healthy individuals, while also reducing the number of synthesized peptides by 78%. In our study on gut phages, we discovered that the immune system develops antibodies to bacteria-infecting viruses in the human gut, 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.

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Liebhoff, A.-M., Venkataraman, T., Morgenlander, W. R., Na, M., Kula, T., Waugh, K., Morrison, C., Rewers, M., Longman, R., Round, J., Elledge, S., Ruczinski, I., Langmead, B., Larman, H. B.. 2023-07-31. Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn. https://doi.org/10.1101/2023.07.30.551179

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