Showing papers by "Jason W. H. Wong published in 2013"

Mass trees: a new phylogenetic approach and algorithm to chart evolutionary history with mass spectrometry.

Abstract: A new phylogenetics approach and algorithm with which to chart the evolutionary history of organisms is presented. It utilizes mass spectral data produced from the proteolytic digestion of proteins, rather than partial or complete gene or translated gene sequences. The concept and validity of the approach is demonstrated herein using both theoretical and experimental mass data, together with the translated gene sequences of the hemagglutinin protein of the influenza virus. A comparison of the mass trees with conventional sequenced-based phylogenetic trees, using two separate tree comparison algorithms, reveals a high degree of similarity and congruence among the trees. Given that the mass map data can be generated more rapidly than gene sequences, even when next generation parallel sequencing is employed, mass trees offer new opportunities and advantages for phylogenetic analysis.

Bioinformatics analysis reveals biophysical and evolutionary insights into the 3-nitrotyrosine post-translational modification in the human proteome.

Abstract: Protein 3-nitrotyrosine is a post-translational modification that commonly arises from the nitration of tyrosine residues. This modification has been detected under a wide range of pathological conditions and has been shown to alter protein function. Whether 3-nitrotyrosine is important in normal cellular processes or is likely to affect specific biological pathways remains unclear. Using GPS-YNO2, a recently described 3-nitrotyrosine prediction algorithm, a set of predictions for nitrated residues in the human proteome was generated. In total, 9.27 per cent of the proteome was predicted to be nitratable (27 922/301 091). By matching the predictions against a set of curated and experimentally validated 3-nitrotyrosine sites in human proteins, it was found that GPS-YNO2 is able to predict 73.1 per cent (404/553) of these sites. Furthermore, of these sites, 42 have been shown to be nitrated endogenously, with 85.7 per cent (36/42) of these predicted to be nitrated. This demonstrates the feasibility of using the predicted dataset for a whole proteome analysis. A comprehensive bioinformatics analysis was subsequently performed on predicted and all experimentally validated nitrated tyrosine. This found mild but specific biophysical constraints that affect the susceptibility of tyrosine to nitration, and these may play a role in increasing the likelihood of 3-nitrotyrosine to affect processes, including phosphorylation and DNA binding. Furthermore, examining the evolutionary conservation of predicted 3-nitrotyrosine showed that, relative to non-nitrated tyrosine residues, 3-nitrotyrosine residues are generally less conserved. This suggests that, at least in the majority of cases, 3-nitrotyrosine is likely to have a deleterious effect on protein function and less likely to be important in normal cellular function.