Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn
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...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-02-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45601-8 |
| _version_ | 1827326895088205824 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Anna-Maria Liebhoff |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:52:06Z |
| format | Article |
| id | doaj.art-f671256a5dbb468ba920e54a8c3dd8ac |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:52:06Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f671256a5dbb468ba920e54a8c3dd8ac2024-03-05T19:40:42ZengNature PortfolioNature Communications2041-17232024-02-0115111210.1038/s41467-024-45601-8Efficient encoding of large antigenic spaces by epitope prioritization with DolphynAnna-Maria Liebhoff0Thiagarajan Venkataraman1William R. Morgenlander2Miso Na3Tomasz Kula4Kathleen Waugh5Charles Morrison6Marian Rewers7Randy Longman8June Round9Stephen Elledge10Ingo Ruczinski11Ben Langmead12H. Benjamin Larman13Department of Computer Science, Johns Hopkins UniversityInstitute of Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins UniversityInstitute of Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins UniversityInstitute of Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins UniversityDepartment of Genetics, Harvard Medical SchoolBarbara Davis Center for Diabetes, University of Colorado DenverBehavioral, Clinical and Epidemiologic Sciences, FHI 360Barbara Davis Center for Diabetes, University of Colorado DenverJill Roberts Institute for Research in IBD, Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell MedicineDepartment of Pathology, Division of Microbiology and Immunology, University of Utah School of MedicineDepartment of Genetics, Harvard Medical SchoolDepartment of Biostatistics, Johns Hopkins UniversityDepartment of Computer Science, Johns Hopkins UniversityInstitute of Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins UniversityAbstract 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.https://doi.org/10.1038/s41467-024-45601-8 |
| spellingShingle | 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 Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn Nature Communications |
| title | Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn |
| title_full | Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn |
| title_fullStr | Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn |
| title_full_unstemmed | Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn |
| title_short | Efficient encoding of large antigenic spaces by epitope prioritization with Dolphyn |
| title_sort | efficient encoding of large antigenic spaces by epitope prioritization with dolphyn |
| url | https://doi.org/10.1038/s41467-024-45601-8 |
| work_keys_str_mv | AT annamarialiebhoff efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT thiagarajanvenkataraman efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT williamrmorgenlander efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT misona efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT tomaszkula efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT kathleenwaugh efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT charlesmorrison efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT marianrewers efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT randylongman efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT juneround efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT stephenelledge efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT ingoruczinski efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT benlangmead efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn AT hbenjaminlarman efficientencodingoflargeantigenicspacesbyepitopeprioritizationwithdolphyn |