title: An Integrated Multiomics Approach to Identify Candidate Antigens for Serodiagnosis of Human Onchocerciasis.
abstract: Improved diagnostic methods are needed to support ongoing efforts to eliminate onchocerciasis (river blindness). This study used an integrated approach to identify adult female Onchocerca volvulus antigens that can be explored for developing serodiagnostic tests. The first step was to develop a detailed multi-omics database of all O. volvulus proteins deduced from the genome, gene transcription data for different stages of the parasite including eight individual female worms (providing gene expression information for 94.8% of all protein coding genes), and the adult female worm proteome (detecting 2126 proteins). Next, female worm proteins were purified with IgG antibodies from onchocerciasis patients and identified using LC-MS with a high-resolution hybrid quadrupole-time-of-flight mass spectrometer. A total of 241 immunoreactive proteins were identified among those bound by IgG from infected individuals but not IgG from uninfected controls. These included most of the major diagnostic antigens described over the past 25 years plus many new candidates. Proteins of interest were prioritized for further study based on a lack of conservation with orthologs in the human host and other helminthes, their expression pattern across the life cycle, and their consistent expression among individual female worms. Based on these criteria, we selected 33 proteins that should be carried forward for testing as serodiagnostic antigens to supplement existing diagnostic tools. These candidates, together with the extensive pan-omics dataset generated in this study are available to the community (http://nematode.net) to facilitate basic and translational research on onchocerciasis.
authors.affiliation: From the ‡McDonnell Genome Institute, Washington University in St Louis, Missouri 63108;
authors.forename: Samantha N
authors.initials: SN
authors.lastname: McNulty
authors.affiliation: From the ‡McDonnell Genome Institute, Washington University in St Louis, Missouri 63108;
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Rosa
authors.affiliation: §Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: Peter U
authors.initials: PU
authors.lastname: Fischer
authors.affiliation: ¶Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Rumsey
authors.affiliation: ¶Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: Petra
authors.initials: P
authors.lastname: Erdmann-Gilmore
authors.affiliation: §Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: Kurt C
authors.initials: KC
authors.lastname: Curtis
authors.affiliation: **Institute for Medical Microbiology, Immunology and Parasitology, University Hospital of Bonn, Bonn, Germany 53127.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: ¶Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; ‖Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: R Reid
authors.initials: RR
authors.lastname: Townsend
authors.affiliation: §Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110;
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Weil
authors.affiliation: From the ‡McDonnell Genome Institute, Washington University in St Louis, Missouri 63108; §Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110; mmitreva@genome.wustl.edu.
authors.forename: Makedonka
authors.initials: M
authors.lastname: Mitreva
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D030541:Databases, Genetic; D042241:Early Diagnosis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D023281:Genomics / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D017181:Onchocerca volvulus / Q000235:genetics / Q000276:immunology*; D009855:Onchocerciasis / Q000175:diagnosis* / Q000276:immunology; D012698:Serologic Tests
chemical_list: D000947:Antigens, Helminth; D007074:Immunoglobulin G