Department of Computer Science and Engineering, Yuan Ze University, Chungli 320, Taiwan.
BMC Bioinformatics. 2010 Oct 29;11:536. doi: 10.1186/1471-2105-11-536.
While occurring enzymatically in biological systems, O-linked glycosylation affects protein folding, localization and trafficking, protein solubility, antigenicity, biological activity, as well as cell-cell interactions on membrane proteins. Catalytic enzymes involve glycotransferases, sugar-transferring enzymes and glycosidases which trim specific monosaccharides from precursors to form intermediate structures. Due to the difficulty of experimental identification, several works have used computational methods to identify glycosylation sites.
By investigating glycosylated sites that contain various motifs between Transmembrane (TM) and non-Transmembrane (non-TM) proteins, this work presents a novel method, GlycoRBF, that implements radial basis function (RBF) networks with significant amino acid pairs (SAAPs) for identifying O-linked glycosylated serine and threonine on TM proteins and non-TM proteins. Additionally, a membrane topology is considered for reducing the false positives on glycosylated TM proteins. Based on an evaluation using five-fold cross-validation, the consideration of a membrane topology can reduce 31.4% of the false positives when identifying O-linked glycosylation sites on TM proteins. Via an independent test, GlycoRBF outperforms previous O-linked glycosylation site prediction schemes.
A case study of Cyclic AMP-dependent transcription factor ATF-6 alpha was presented to demonstrate the effectiveness of GlycoRBF. Web-based GlycoRBF, which can be accessed at http://GlycoRBF.bioinfo.tw, can identify O-linked glycosylated serine and threonine effectively and efficiently. Moreover, the structural topology of Transmembrane (TM) proteins with glycosylation sites is provided to users. The stand-alone version of GlycoRBF is also available for high throughput data analysis.
在生物系统中发生的 O 连接糖基化影响蛋白质折叠、定位和运输、蛋白质溶解度、抗原性、生物活性以及膜蛋白上的细胞-细胞相互作用。催化酶涉及糖基转移酶、糖基转移酶和糖苷酶，它们从前体中修剪特定的单糖以形成中间结构。由于实验鉴定的困难，一些工作已经使用计算方法来鉴定糖基化位点。
通过研究跨膜（TM）和非跨膜（非-TM）蛋白之间含有各种基序的糖基化位点，本工作提出了一种新方法 GlycoRBF，该方法使用具有显著氨基酸对（SAAPs）的径向基函数（RBF）网络来识别 TM 蛋白和非-TM 蛋白上的 O 连接糖基化丝氨酸和苏氨酸。此外，还考虑了膜拓扑结构来减少 TM 蛋白上糖基化假阳性。基于五重交叉验证的评估，在识别 TM 蛋白上的 O 连接糖基化位点时，考虑膜拓扑结构可以减少 31.4%的假阳性。通过独立测试，GlycoRBF 优于以前的 O 连接糖基化位点预测方案。
提出了一个环磷酸腺苷依赖性转录因子 ATF-6alpha 的案例研究，以证明 GlycoRBF 的有效性。可在 http://GlycoRBF.bioinfo.tw 访问基于网络的 GlycoRBF，它可以有效地识别 O 连接糖基化丝氨酸和苏氨酸。此外，还为用户提供了具有糖基化位点的跨膜（TM）蛋白的结构拓扑。GlycoRBF 的独立版本也可用于高通量数据分析。
