TY - JOUR
T1 - An integrated multiomics approach to identify candidate antigens for serodiagnosis of human onchocerciasis
AU - McNulty, Samantha N.
AU - Rosa, Bruce A.
AU - Fischer, Peter U.
AU - Rumsey, Jeanne M.
AU - Erdmann-Gilmore, Petra
AU - Curtis, Kurt C.
AU - Specht, Sabine
AU - Townsend, R. Reid
AU - Weil, Gary J.
AU - Mitreva, Makedonka
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/12
Y1 - 2015/12
N2 - 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-offlight 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.
AB - 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-offlight 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.
UR - http://www.scopus.com/inward/record.url?scp=84948678492&partnerID=8YFLogxK
U2 - 10.1074/mcp.M115.051953
DO - 10.1074/mcp.M115.051953
M3 - Article
C2 - 26472727
AN - SCOPUS:84948678492
SN - 1535-9476
VL - 14
SP - 3224
EP - 3233
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 12
ER -