Systematic analysis of human lysine acetylation proteins and accurate prediction of human lysine acetylation through bi-relative adapted binomial score Bayes feature representation

Abstract

Lysine acetylation is a reversible post-translational modification (PTM) which has been linked to many biological and pathological implications. Hence, localization of lysine acetylation is essential for deciphering the mechanism of such implications. Whereas many acetylated lysines in human proteins have been localized through experimental approaches in wet lab, it still fails to reach completion. In the present study, we proposed a novel feature extraction approach, bi-relative adapted binomial score Bayes (BRABSB), combined with support vector machines (SVMs) to construct a human-specific lysine acetylation predictor, which yields, on average, a sensitivity of 83.91%, a specificity of 87.25% and an accuracy of 85.58%, in the case of 5-fold cross validation experiments. Results obtained through the validation on independent data sets show that the proposed approach here outperforms other existing lysine acetylation predictors. Furthermore, due to the fact that global analysis of human lysine acetylproteins, which would ultimately facilitate the systematic investigation of the biological and pathological consequences associated with lysine acetylation events, remains to be resolved, we made an attempt to systematically analyze human lysine acetylproteins, demonstrating their diversity with respect to subcellular localization as well as biological process and predominance by "binding" in terms of molecular function. Our analysis also revealed that human lysine acetylproteins are significantly enriched in neurodegenerative disorders and cancer pathways. Remarkably, lysine acetylproteins in mitochondria are significantly related to neurodegenerative disorders and those in the nucleus are instead significantly involved in pathways in cancers, all of which might ultimately provide novel global insights into such pathological processes for the therapeutic purpose. The web server is deployed at http://www.bioinfo.bio.cuhk.edu.hk/bpbphka.

Regulation, Function, and Detection of Protein Acetylation in Bacteria

“…It is worth considering that the identification of the acetylated sites can be influenced by the antibodies used for immunoaffinity enrichment of the modified peptides. However, the observations in bacteria seem to contrast other eukaryotic acetylation motifs, such as the glycine-rich histone acetylation motifs and the reported enrichment for aromatic and basic residues in other linear nuclear motifs (1,2,(73)(74)(75)(76). There are two possibilities for the significance of the enrichment in acidic residues in the vicinity of an acetylation site in bacteria.…”

MOF Acetylates the Histone Demethylase LSD1 to Suppress Epithelial-to-Mesenchymal Transition

“…Two in silico online programs, LAceP and BRABSB-PHKA, both predicted potential lysine (K) acetylation sites in human LSD1, including K432 and K436 (http://www.scbit.org/iPTM) (Hou et al, 2014;Shao et al, 2012). Global proteomics also uncovered acetylation of LSD1 K432, K433, and K436 (http://www.…”

SIRT1 contributes to aldose reductase expression through modulating NFAT5 under osmotic stress: In vitro and in silico insights

“…10 different algorithms were used; KacePred [48], PAIL [49], ASEB [50,51], Predmod [52], BRABSB-PHKA [53], PSKAcePred [54], PLMLA [55], PHOSIDA [56], EnsemblePail [57] and Lys Acet [58], which are, to our knowledge, the most frequently and widely used/cited methods for prediction of lysine acetylation sites. Threshold values were taken as stringent as possible for all predictions (Supplementary Table 1).…”