Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array
Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterog...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Frontiers Media
2017
|
| _version_ | 1797094036550451200 |
|---|---|
| author | Darton, T Baker, S Randall, A Dongol, S Karkey, A Voysey, M Carter, M Jones, C Trappl, K Pablo, J Hung, C Teng, A Shandling, A Le, T Walker, C Molina, D Andrews, J Arjyal, A Basnyat, B Pollard, A Blohmke, C |
| author_facet | Darton, T Baker, S Randall, A Dongol, S Karkey, A Voysey, M Carter, M Jones, C Trappl, K Pablo, J Hung, C Teng, A Shandling, A Le, T Walker, C Molina, D Andrews, J Arjyal, A Basnyat, B Pollard, A Blohmke, C |
| author_sort | Darton, T |
| collection | OXFORD |
| description | Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30), and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100) from other febrile bacteremia (n = 52) in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71) or 3 antigens (0.87), although IgA responses to LPS also performed well (0.88). Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever. |
| first_indexed | 2024-03-07T04:08:32Z |
| format | Journal article |
| id | oxford-uuid:c707a9b4-d499-4a0a-9f48-3ac8eeb9e204 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T04:08:32Z |
| publishDate | 2017 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:c707a9b4-d499-4a0a-9f48-3ac8eeb9e2042022-03-27T06:42:16ZIdentification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome arrayJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c707a9b4-d499-4a0a-9f48-3ac8eeb9e204Symplectic Elements at OxfordFrontiers Media2017Darton, TBaker, SRandall, ADongol, SKarkey, AVoysey, MCarter, MJones, CTrappl, KPablo, JHung, CTeng, AShandling, ALe, TWalker, CMolina, DAndrews, JArjyal, ABasnyat, BPollard, ABlohmke, CCurrent diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30), and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100) from other febrile bacteremia (n = 52) in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71) or 3 antigens (0.87), although IgA responses to LPS also performed well (0.88). Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever. |
| spellingShingle | Darton, T Baker, S Randall, A Dongol, S Karkey, A Voysey, M Carter, M Jones, C Trappl, K Pablo, J Hung, C Teng, A Shandling, A Le, T Walker, C Molina, D Andrews, J Arjyal, A Basnyat, B Pollard, A Blohmke, C Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title | Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title_full | Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title_fullStr | Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title_full_unstemmed | Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title_short | Identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| title_sort | identification of novel serodiagnostic signatures of typhoid fever using a salmonella proteome array |
| work_keys_str_mv | AT dartont identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT bakers identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT randalla identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT dongols identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT karkeya identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT voyseym identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT carterm identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT jonesc identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT trapplk identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT pabloj identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT hungc identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT tenga identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT shandlinga identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT let identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT walkerc identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT molinad identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT andrewsj identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT arjyala identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT basnyatb identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT pollarda identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray AT blohmkec identificationofnovelserodiagnosticsignaturesoftyphoidfeverusingasalmonellaproteomearray |