A computational pipeline for diagnostic biomarker discovery in the human pathogen Trypanosoma cruzi
© Carmona et al; licensee BioMed Central Ltd. 2010
Published: 07 December 2010
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas' disease, endemic in 18 countries in Central and South America. Transmission also occurs in non-endemic countries by way of blood transfusion and organ transplantation. Diagnosis of American trypanosomiasis is based on the detection of antibodies directed against T. cruzi antigens. In this work we mined the T. cruzi genome sequence to identify new peptidic diagnostic biomarkers.
We show that our integrative method outperforms alternative antigen prioritizations based on individual properties (such as B-cell epitope predictors alone). Our genome-wide prioritization uncovered more than 300 promising biomarker candidates. 200 high-scoring peptides corresponding mostly to hypothetical proteins were selected for immunological validation, along with 40 peptides derived from previously validated B-cell epitopes and an additional set of 40 low-scoring peptides as controls. Preliminary results based on microarray images revealed that ~25% (49/200) of the candidate peptides reacted specifically against the positive sera pools assayed.
The developed bioinformatic approach proved to be successful, leading from a genome-wide prioritization to the identification of novel peptidic antigens with diagnostic potential. Moreover, the algorithm may be used to prioritize biomarkers in other pathogen species.
This work was funded by Universidad de San Martín (grant PROG07F/1) and the “Special Programme for Research and Training in Tropical Diseases (UNICEF/UNDP/World Bank/WHO)”.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.