Dataset Information

The identification of onchocerciasis biomarker candidates directly in human serum and urine

ABSTRACT: Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current mass drug administration treatments do not kill female O. volvulus worms, and common diagnostic tests cannot reliably assess the viability of adult worms. This lack of sensitivity for active infections presents an urgent need for better diagnostic tests to monitor the efficacy of new treatments and ongoing mass drug administration. Serum samples from individuals infected with O. volvulus (n = 8), and from uninfected individuals (n = 7) were examined by deep scale proteomics, including the use of a timsTOF Pro mass spectrometer. Data were interrogated for O. volvulus proteins present in infected but not uninfected samples. Among all detected proteins, 19 high-priority candidate biomarkers were identified in the serum of 3 or more O. volvulus-infected samples (not present in uninfected) that were supported by two or more unique peptides. Comprehensive functional annotation, RNA-seq based transcriptional profiling and taxonomic conservation/diversification characterized the detected proteins in more detail. 15 peptides from 11 of the top 19 proteins were validated by parallel MS/MS (Orbitrap) with isotope-labeled synthetic peptides. One candidate was detected with eight unique peptides in five different serum samples. Additional MS/MS samples have shown that peptides from 4 of the top 6 candidate biomarkers were also detected in urine samples from onchocerciasis patients. We are now working to develop practical assays for the most promising candidates that may be useful for diagnosis of active infections and for monitoring efficacy of new treatments in clinical trials.

ORGANISM(S): Homo Sapiens Onchocerca Volvulus

SUBMITTER: Peter U Fisher

PROVIDER: PXD033659 | iProX | Tue Nov 22 00:00:00 GMT 2022

REPOSITORIES: iProX

ACCESS DATA

Publications

Direct Proteomic Detection and Prioritization of 19 Onchocerciasis Biomarker Candidates in Humans.

Rosa Bruce A BA Curtis Kurt K Erdmann Gilmore Petra P Martin John J Zhang Qiang Q Sprung Robert R Weil Gary J GJ Townsend R Reid RR Fischer Peter U PU Mitreva Makedonka M

Molecular & cellular proteomics : MCP 20221123 1

Onchocerca volvulus, the causative agent of onchocerciasis, infects over 20 million people and can cause severe dermatitis and ocular conditions including blindness. Current treatments employed in mass drug administration programs do not kill adult female worms, and common diagnostic tests cannot reliably assess viability of adult worms. There is an urgent need for better diagnostic tests to facilitate monitoring the efficacy of new treatments and disease elimination efforts. Here, eight plasma ...[more]

PMID: 36435333

Similar Datasets

Project description:Dengue and Zika are two mosquito-borne diseases of great concern, affecting mainly the tropical and subtropical regions worldwide. The arrival of Zika virus (ZIKV) in dengue virus (DENV) endemic areas imposed challenges for differential diagnosis and the development of candidate vaccines. The use of peptides has shown great potential to achieve these goals. We aimed to identify the linear epitope profile recognized by the serum samples of dengue and Zika patients in the E and NS1 proteins of DENV and ZIKV to select peptides with the potential for the development of diagnostic tests and vaccines. Analysis of a peptide microarray platform with serum samples of dengue and Zika patients demonstrated that the epitopes were evenly distributed across the entire viral proteins, showing no preference for particular regions. However, several epitopes were within epitope hot spots constituted by clusters of peptides recognized in more than 30% of the sub-arrays analyzed with individual or pools of serum samples. The serum samples of dengue and Zika patients showed a high level of cross-reaction for epitopes in the DENV and ZIKV proteins. Analysis of an additional peptide microarray platform containing selected peptides based on the results of the first screening showed that three peptides (DENV: TQGEPSLNEEQDKRF and TQTVGPWHLGKLEID; ZIKV: LELDPPFGDSYIVIG), highly specific for their cognate viruses (p<0.05), were within the epitope hot spots; however, these peptides showed low detection rates (32.5, 35.0, and 28.6%, respectively). We also found two peptides (DENV: WEVEDYGFGVFTTNI and LELDFDLCEGTTVVV) in the epitope hot spots detected by both dengue and Zika patients with similarly high rates (arbitrary detection rate cut-off threshold of ≥40%). The epitope hot spots harbor several immunodominant epitopes recognized by a higher number of individuals when compared to the 15 aa sequence peptides. Therefore, the entire epitope hot spots, spanning up to ~30 aa, would have more potential than peptides of only 15 aa to serve as antigens in diagnostic tests and vaccine developments.

Dataset Information

The identification of onchocerciasis biomarker candidates directly in human serum and urine

Publications

Direct Proteomic Detection and Prioritization of 19 Onchocerciasis Biomarker Candidates in Humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure