title: Prediction of Protein Lysine Acylation by Integrating Primary Sequence Information with Multiple Functional Features.
abstract: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic methods have been widely used to identify lysine acylation proteins. However, these experimental approaches often fail to detect proteins that are in low abundance or absent in specific biological samples. To circumvent these problems, we developed a computational method to predict lysine acylation, including acetylation, malonylation, succinylation, and glutarylation. The prediction algorithm integrated flanking primary sequence determinants and evolutionary conservation of acylated lysine as well as multiple protein functional annotation features including gene ontology, conserved domains, and protein-protein interactions. The inclusion of functional annotation features increases predictive power oversimple sequence considerations for four of the acylation species evaluated. For example, the Matthews correlation coefficient (MCC) for the prediction of malonylation increased from 0.26 to 0.73. The performance of prediction was validated against an independent data set for malonylation. Likewise, when tested with independent data sets, the algorithm displayed improved sensitivity and specificity over existing methods. Experimental validation by Western blot experiments and LC-MS/MS detection further attested to the performance of prediction. We then applied our algorithm on to the mouse proteome and reported the global-scale prediction of lysine acetylation, malonylation, succinylation, and glutarylation, which should serve as a valuable resource for future functional studies.
authors: Yipeng
authors: Y
authors: Du
authors: Zichao
authors: Z
authors: Zhai
authors: Ying
authors: Y
authors: Li
authors: Ming
authors: M
authors: Lu
authors: Tanxi
authors: T
authors: Cai
authors: University of Chinese Academy of Sciences , Beijing 100049, China.
authors: Bo
authors: B
authors: Zhou
authors: College of Information Science and Engineering, Ocean University of China , Qingdao, China.
authors: Lei
authors: L
authors: Huang
authors: Taotao
authors: T
authors: Wei
authors: Tingting
authors: T
authors: Li
mesh_terms: D000215:Acylation; D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid; D019295:Computational Biology / Q000379:methods*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D011506:Proteins; D008239:Lysine
keywords: PTM; acetylation; acylation; glutarylation; malonylation; posttranslational modification; prediction; proteomics; succinylation