Proteome-wide discovery of novel diagnostic antigens for coccidioidomycosis
- 1Translational Genomics Research Institute
Abstract
Coccidioidomycosis, commonly called Valley Fever (VF), caused by Coccidioides spp., is an understudied fungal disease that accounts for a substantial fraction of pneumonias in endemic areas. Diagnosis remains challenging because the mainstay of diagnosis is serology, and current assays have modest sensitivity in early infection. Discovery of new antigens could improve serologic detection early in disease. Here, we use PepSeq, a DNA-programmable serology platform, to represent the complete proteome of Coccidioides within a library of 244,000 DNA-barcoded peptides. By profiling antibody reactivity at the protein and epitope levels in VF patients, naturally infected pigtail macaques, and healthy controls, we identify numerous previously-unrecognized antigens and epitopes, including some shared between humans and macaque responses. When translated into a pooled peptide ELISA, we show that a subset of identified antigens can discriminate VF cases from controls in an independent cohort with high accuracy (AUC = 0.91). These findings establish high-dimensional peptide serology as a scalable approach for fungal antigen discovery and identify new targets for improved VF diagnosis.
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BibTeX
@misc{elko2026proteomewide,
title = {{Proteome-wide discovery of novel diagnostic antigens for coccidioidomycosis}},
author = {E. Elko and L. Ryle and G. A. Nelson and N. G. Sarbo and C. E. Harms and E. Kelley and M. N. Fredericks and P. Keim and K. Knox and M. Kala and D. H. Fuller and E. W. Settles and B. M. Barker and D. M. Magee and D. F. Lake and T. E. Grys and G. R. Thompson and J. Altin and J. T. Ladner and H. L. Mead},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.764335},
url = {https://www.biorxiv.org/content/10.64898/2026.11.05.764335v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Proteome-wide discovery of novel diagnostic antigens for coccidioidomycosis
AU - E. Elko
AU - L. Ryle
AU - G. A. Nelson
AU - N. G. Sarbo
AU - C. E. Harms
AU - E. Kelley
AU - M. N. Fredericks
AU - P. Keim
AU - K. Knox
AU - M. Kala
AU - D. H. Fuller
AU - E. W. Settles
AU - B. M. Barker
AU - D. M. Magee
AU - D. F. Lake
AU - T. E. Grys
AU - G. R. Thompson
AU - J. Altin
AU - J. T. Ladner
AU - H. L. Mead
PY - 2026
DA - 2026/11/05
PB - bioRxiv
DO - 10.64898/2026.11.05.764335
UR - https://www.biorxiv.org/content/10.64898/2026.11.05.764335v1
AB - Coccidioidomycosis, commonly called Valley Fever (VF), caused by Coccidioides spp., is an understudied fungal disease that accounts for a substantial fraction of pneumonias in endemic areas. Diagnosis remains challenging because the mainstay of diagnosis is serology, and current assays have modest sensitivity in early infection. Discovery of new antigens could improve serologic detection early in disease. Here, we use PepSeq, a DNA-programmable serology platform, to represent the complete proteome of Coccidioides within a library of 244,000 DNA-barcoded peptides. By profiling antibody reactivity at the protein and epitope levels in VF patients, naturally infected pigtail macaques, and healthy controls, we identify numerous previously-unrecognized antigens and epitopes, including some shared between humans and macaque responses. When translated into a pooled peptide ELISA, we show that a subset of identified antigens can discriminate VF cases from controls in an independent cohort with high accuracy (AUC = 0.91). These findings establish high-dimensional peptide serology as a scalable approach for fungal antigen discovery and identify new targets for improved VF diagnosis.
ER -