TY - JOUR
T1 - Deconvoluting virome-wide antibody epitope reactivity profiles
AU - Monaco, Daniel R.
AU - Kottapalli, Sanjay V.
AU - Breitwieser, Florian P.
AU - Anderson, Danielle E.
AU - Wijaya, Limin
AU - Tan, Kevin
AU - Chia, Wan Ni
AU - Kammers, Kai
AU - Caturegli, Patrizio
AU - Waugh, Kathleen
AU - Roederer, Mario
AU - Petri, Michelle
AU - Goldman, Daniel W.
AU - Rewers, Marian
AU - Wang, Lin Fa
AU - Larman, H. Benjamin
N1 - Publisher Copyright:
© 2021
PY - 2022/1
Y1 - 2022/1
N2 - Background: Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display technology for profiling antibody binding to a library of peptides designed to span the human virome. Previous VirScan analytical approaches did not carefully account for antibody cross-reactivity among sequences shared by related viruses or for the disproportionate representation of individual viruses in the library. Methods: Here we present the AntiViral Antibody Response Deconvolution Algorithm (AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection with species-level resolution by considering sequence alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. We further assessed AVARDA's utility in associating viral infection with type 1 diabetes and lupus. Findings: By comparing acute and convalescent sera, AVARDA successfully confirmed or detected encephalitis-associated responses to human herpesviruses 1, 3, 4, 5, and 6, improving the rate of diagnosing viral encephalitis in this cohort by 44%. AVARDA analyses of VirScan data from the type 1 diabetes and lupus cohorts implicated enterovirus and herpesvirus infections, respectively. Interpretation: AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases. Funding: This work was made possible by support from the National Institutes of Health (NIH), the US Army Research Office, the Singapore Infectious Diseases Initiative (SIDI), the Singapore Ministry of Health's National Medical Research Council (NMRC) and the Singapore National Research Foundation (NRF).
AB - Background: Comprehensive characterization of exposures and immune responses to viral infections is critical to a basic understanding of human health and disease. We previously developed the VirScan system, a programmable phage-display technology for profiling antibody binding to a library of peptides designed to span the human virome. Previous VirScan analytical approaches did not carefully account for antibody cross-reactivity among sequences shared by related viruses or for the disproportionate representation of individual viruses in the library. Methods: Here we present the AntiViral Antibody Response Deconvolution Algorithm (AVARDA), a multi-module software package for analyzing VirScan datasets. AVARDA provides a probabilistic assessment of infection with species-level resolution by considering sequence alignment of all library peptides to each other and to all human viruses. We employed AVARDA to analyze VirScan data from a cohort of encephalitis patients with either known viral infections or undiagnosed etiologies. We further assessed AVARDA's utility in associating viral infection with type 1 diabetes and lupus. Findings: By comparing acute and convalescent sera, AVARDA successfully confirmed or detected encephalitis-associated responses to human herpesviruses 1, 3, 4, 5, and 6, improving the rate of diagnosing viral encephalitis in this cohort by 44%. AVARDA analyses of VirScan data from the type 1 diabetes and lupus cohorts implicated enterovirus and herpesvirus infections, respectively. Interpretation: AVARDA, in combination with VirScan and other pan-pathogen serological techniques, is likely to find broad utility in the epidemiology and diagnosis of infectious diseases. Funding: This work was made possible by support from the National Institutes of Health (NIH), the US Army Research Office, the Singapore Infectious Diseases Initiative (SIDI), the Singapore Ministry of Health's National Medical Research Council (NMRC) and the Singapore National Research Foundation (NRF).
KW - Antibody profiling
KW - Encephalitis
KW - Phage ImmunoPrecipitation Sequencing (PhIP-Seq)
KW - Systemic lupus erythematosus
KW - Type 1 diabetes
KW - VirScan
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U2 - 10.1016/j.ebiom.2021.103747
DO - 10.1016/j.ebiom.2021.103747
M3 - Article
C2 - 34922324
AN - SCOPUS:85121270586
SN - 2352-3964
VL - 75
JO - EBioMedicine
JF - EBioMedicine
M1 - 103747
ER -