MAPRes: Mining association patterns among preferred amino acid residues in the vicinity of amino acids targeted for post‐translational modifications

Abstract

Post-translational modification (PTM) of a protein is an important event in regulating cellular functions. An algorithm, MAPRes, has been developed for mining associations among PTM sites and the preferred amino acids in their vicinity. The algorithm has been implemented to O-glycosylation and O-phosphorylation data (phosphorylated/glycosylated Ser/Thr/Tyr). The association patterns mined by MAPRes demonstrate significant correlations and the results are in conformity with the existing methods. These association rules/patterns will be helpful in predicting the sequences/motifs involved for specific PTMs in proteins.

Phosphoproteome sequence analysis and significance: Mining association patterns around phosphorylation sites utilizing MAPRes

“…Patterns were mined at different support levels and each association pattern was associated with a confidence level. In the present study, the support level reflected the percent data containing the pattern mined by MAPRes, whereas confidence of a mined pattern was measured as a conditional probability of occurrence, as described in the MAPRes methodology [Ahmad et al, 2008a]. MAPRes was applied for preference estimation and association rules mining to phosphorylated S/T/Y Phospho.ELM 7.0 data, with and without kinase information.…”

“…Thus, a machine learning algorithm can result in a better prediction accuracy of PTMs (e.g., phosphorylation) when it is based on features extracted with the proper statistical model or when the learning algorithm is trained on the whole PTM data. The approach of MAPRes is also based on the fact that significantly preferred amino acids in the vicinity of PTM sites are utilized for pattern mining/extraction [Ahmad et al, 2008a]. These patterns will be utilized in future for the development and application of an algorithm for training neural networks to achieve maximum prediction accuracy.…”

“…To overcome this problem, an alternative approach for describing enzyme-substrate relation is the analysis of the primary sequence of substrate proteins and that of enzymes. One such approach seeks to identify the significantly preferred amino acids in the vicinity of a posttranslational modification (PTM) site and then developing a correlation between the significantly preferred amino acids in the vicinity of a PTM site by resorting to the association rule mining technique [Ahmad et al, 2008a]. Besides determining the preferred amino acids in the vicinity of a PTM site, this method establishes whether or not an association between preferred sites and target of phosphorylation actually exists.…”

“…The main shortcoming of this approach, however, was that the analysis was restricted to merely extracting the patterns of the substrates for S/T and Y kinases. To overcome this limitation, it is possible to perform an analysis that provides both general and specific patterns for S/T/Y phosphorylation and specifically so for different kinase groups, families, and individual members, by using the MAPRes technique [Ahmad et al, 2008a].…”

“…The later version of this database Phospho.ELM 7.0 [Diella et al, 2008] is a phosphorylation sites database that contains 3-4 times more data of experimentally determined protein phosphorylation sites than the previous version (3.0) [Diella et al, 2004]. In this study, phosphorylation data of Phospho.ELM 7.0 [Diella et al, 2008] have been analyzed utilizing MAPRes [Ahmad et al, 2008a] both for all phosphorylated S/T/Y and for different kinase substrate sites. The association patterns mined by MAPRes for all phosphorylated S/T/Y (without kinase information) are consistent with the previous findings with additional patterns compared to the previous analysis [Ahmad et al, 2008b].…”