CONICET | Buscador de Institutos y Recursos Humanos

In order to identify novel markers for serodiagnosis of Chagas disease, we have produced a ranked list of potential antigens from the genome of the protozoan parasite Trypanosoma cruzi. The major challenge is to find novel antigens to improve diagnostic specificity and possibly discriminate between different lineages of T. cruzi, which present different ecoepidemiology. The methodology consisted in assessing a set of criteria in annotated protein sequences in the reference genome of the CL Brener strain of T. cruzi (19613, including hypotheticals). Some of these criteria are: the more likely subcellular localization for a given protein (based on prediction of signal peptide, glycosylphosphatidylinositol anchor, etc.), the presence and characteristics of internal repetitive motifs in tandem, the estimated number of copies in the genome, the presence or absence of similarity against Leishmania and human proteins, presence and density of predicted antigenic epitopes, presence and density of putative O-glycosylation sites, predicted secondary structure motifs. Each protein is assigned a score or penalty according to whether or not the criteria are met. The final result is a list of proteins ordered by a global score, calculated as a weighted sum of the scores or penalties that corresponds to each criterion. The already known immunogenic antigens (e.g. SAPA, surface antigen 2(B13), Tc40) ranked together with the highest scoring proteins, supporting the criteria and methods applied. The prioritization is done on a customized version of the web tool TDRTargets.org specially designed for this purpose, allowing us to quickly recalculate the ranked list, assigning different weights to each criterion. In this work we present a first approach to the priortization, that will be complemented with information on genetic variation in T. cruzi, that is being generated in the lab.

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