Abstract
BackgroundProtein phosphorylation modulates protein function in organisms at all levels of complexity. Parasites of the Leishmania genus undergo various developmental transitions in their life cycle triggered by changes in the environment. The molecular mechanisms that these organisms use to process and integrate these external cues are largely unknown. However Leishmania lacks transcription factors, therefore most regulatory processes may occur at a post-translational level and phosphorylation has recently been demonstrated to be an important player in this process. Experimental identification of phosphorylation sites is a time-consuming task. Moreover some sites could be missed due to the highly dynamic nature of this process or to difficulties in phospho-peptide enrichment.ResultsHere we present PhosTryp, a phosphorylation site predictor specific for trypansomatids. This method uses an SVM-based approach and has been trained with recent Leishmania phosphosproteomics data. PhosTryp achieved a 17% improvement in prediction performance compared with Netphos, a non organism-specific predictor. The analysis of the peptides correctly predicted by our method but missed by Netphos demonstrates that PhosTryp captures Leishmania-specific phosphorylation features. More specifically our results show that Leishmania kinases have sequence specificities which are different from their counterparts in higher eukaryotes. Consequently we were able to propose two possible Leishmania-specific phosphorylation motifs.We further demonstrate that this improvement in performance extends to the related trypanosomatids Trypanosoma brucei and Trypanosoma cruzi. Finally, in order to maximize the usefulness of PhosTryp, we trained a predictor combining all the peptides from L. infantum, T. brucei and T. cruzi.ConclusionsOur work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at http://phostryp.bio.uniroma2.it
Highlights
Protein phosphorylation modulates protein function in organisms at all levels of complexity
The results with NetphosK were even worse, with an AUC of 0,56 on T. cruzi and 0.55 on T. brucei. These results show that PhosTryp, which was Comparison of the predictors on a Trypanosoma brucei dataset trained on Leishmania infantum, performs better than generic predictors when applied to this group of organisms
Development of a predictor for organisms of the family Trypanosomatidae Our results show that a predictor trained on Leishmania-specific data performs better than generic predictors even when applied to the related organisms T. cruzi and T. brucei
Summary
Protein phosphorylation modulates protein function in organisms at all levels of complexity. Protein phosphorylation is the most abundant posttranslational modification in both prokaryotic and eukaryotic organisms This process is regulated through the enzymatic activities of protein kinases and phosphatases. In-depth analyses of the phosphoproteome of parasitic protozoa has only recently been initiated in African Trypanosomes and Leishmania [6,7,8,9,10]. These studies reported phosphorylation sites whose sequence did not match known kinase recognition motifs, e.g. 25% of the sites identified by Nett et al [6] were not recognized by either Scansite [11] or Netphos [12]. For instance Hem et al [7] showed that a number of chaperones and heat-shock proteins which are very conserved from Leishmania to human possess parasitespecific phosphorylation sites
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