PlantPhos: Using maximal dependence decomposition to identify plant phosphorylation sites with substrate sit specificity

• Main Authors: Lee, Tzong-Yi, Bretana, Neil Arvin B., Lu, Cheng-Tsung
• Format: text
• Published: Animo Repository 2011
• Subjects: Phosphorylation; Plant Biology
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/13568
• Institution: De La Salle University

Background: Protein phosphorylation catalyzed by kinases plays crucial regulatory roles in intracellular signal transduction. Due to the difficulty in performing high-throughput mass spectrometry-based experiment, there is a desire to predict phosphorylation sites using computational methods. However, previous studies regarding in silico prediction of plant phosphorylation sites lack the consideration of kinase-specific phosphorylation data. Thus, we are motivated to propose a new method that investigates different substrate specificities in plant phosphorylation sites. Results: Experimentally verified phosphorylation data were extracted from TAIR9 - a protein database containing 3006 phosphorylation data from the plant species Arabidopsis thaliana. In an attempt to investigate the various substrate motifs in plant phosphorylation, maximal dependence decomposition (MDD) is employed to cluster a large set of phosphorylation data into subgroups containing significantly conserved motifs. Profile hidden Markov model (HMM) is then applied to learn a predictive model for each subgroup. Cross-validation evaluation on the MDD-clustered HMMs yields an average accuracy of 82.4% for serine, 78.6% for threonine, and 89.0% for tyrosine models. Moreover, independent test results using Arabidopsis thaliana phosphorylation data from UniProtKB/Swiss-Prot show that the proposed models are able to correctly predict 81.4% phosphoserine, 77.1% phosphothreonine, and 83.7% phosphotyrosine sites. Interestingly, several MDD-clustered subgroups are observed to have similar amino acid conservation with the substrate motifs of well-known kinases from Phospho.ELM - a database containing kinase-specific phosphorylation data from multiple organisms. Conclusions: This work presents a novel method for identifying plant phosphorylation sites with various substrate motifs. Based on cross-validation and independent testing, results show that the MDD-clustered models outperform models trained without using MDD. The proposed method has been implemented as a web-based plant phosphorylation prediction tool, PlantPhos (http://csb.cse.yzu.edu.tw/PlantPhos/). Additionally, two case studies have been demonstrated to further evaluate the effectiveness of PlantPhos.