PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae
- Equal contributors
1 Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome
2 Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel
3 Institut Pasteur, CNRS URA 2581, Unité de Parasitologie moléculaire et Signalisation, 75015 Paris, France
Citation and License
BMC Genomics 2011, 12:614 doi:10.1186/1471-2164-12-614Published: 19 December 2011
Protein 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.
Here 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.