LAFEM: A scoring model to evaluate functional landscape of lysine acetylome

Mol Cell Proteomics. 2023 Dec 15:100700. doi: 10.1016/j.mcpro.2023.100700. Online ahead of print.ABSTRACTProtein lysine acetylation is a critical post-translation modification (PTM) involved in a wide range of biological processes. To date, about 20,000 acetylation sites of Homo sapiens were identified through mass spectrometry-based proteomic technology but more than 95% of them have unclear functional annotations due to the lack of existing prioritization strategy to assess the functional importance of the acetylation sites on large-scale. Hence, we established a lysine acetylation functional evaluating model (LAFEM) by considering 8 critical features surrounding lysine acetylation site to high-throughput estimate the functional importance of given acetylation sites. This was achieved by selecting one of the Random-Forest models with the best performance in 10-folds cross-validation on under-sampled training dataset. The global analysis demonstrated that the molecular environment of acetylation sites with high acetylation functional scores (AFSs) mainly had the features of larger solvent accessible surface area (SASA), stronger hydrogen-bonding-donating abilities, near motif and domain, higher homology and disordered degree. Importantly, LAFEM performed well in validation dataset and acetylome, showing good accuracy to screen out fitness directly relevant acetylation sites and assisting to explain the core reason for the difference between biological models from the perspec...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Source Type: research