Biomedical Center, School of Electronics Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China.
Cell Biochem Biophys. 2011 Jul;60(3):199-207. doi: 10.1007/s12013-010-9140-x.
CREB5 computational regulation network construction and analysis of frontal cortex of HIV encephalitis (HIVE) is very useful to identify novel markers and potential targets for prognosis and therapy. By integration of gene regulatory network infer and the database for annotation, visualization and integrated discovery we identified and constructed significant molecule CREB5 regulation network from 12 frontal cortex of HIVE-control patients and 16 HIVE in the same GEO Dataset GDS1726. Our result verified CREB5 biological regulation module in the upstream of frontal cortex of HIVE-control patients (MAPKAPK3 activation; DGKG, LY96, TNFRSF11B inhibition) and downstream (ATP6V0E1, CFB, DGKG, MX1, TGFBR3 activation; LGALS3BP, RASGRP3, RDX, STAT1 inhibition), whereas in the upstream of frontal cortex of HIVE (BST2, CFB, LCAT, TNFRSF11B activation; CFHR1, LY96 inhibition) and downstream (GAS1, LCAT, LGALS3BP, NFAT5, VEZF1, ZNF652 activation; DGKG, IFITM1, LY96, TNFRSF11B inhibition). Importantly, we datamined that CREB5 regulation cluster of HIVE was involved in inflammatory response, proteolysis, biological adhesion, and negative regulation of biological process (only in HIVE terms) without positive regulation of cellular process, phosphotransferase, kinase, post-translational protein modification, ATP binding, transmembrane protein, calcium ion binding, acetylation, and hydrolase activity (only in HIVE-control patients terms), the condition was vital to inflammation and cognition impairment of HIVE. Our result demonstrated that common terms in both HIVE-control patients and HIVE included biological regulation, phosphoprotein, metabolic process, zinc, biosynthetic process, organelle, signal transduction, defense response, membrane, secreted, signal peptide, and glycoprotein, and these terms were more relative to inflammation and cognition impairment, therefore we deduced the stronger CREB5 regulation network in HIVE consistent with our number computation. It would be necessary of the stronger CREB5 regulation function to inflammation and cognition impairment of HIVE.
构建和分析 HIV 脑炎（HIVE）额叶皮质的 CREB5 计算调节网络对于识别新型标志物和预后及治疗的潜在靶点非常有用。通过基因调控网络推断与注释、可视化和综合发现数据库的整合，我们从 12 例 HIVE-对照患者和 16 例相同 GEO 数据集 GDS1726 中的 HIVE 额叶皮质中鉴定并构建了重要的 CREB5 调节网络。我们的结果验证了 CREB5 在 HIVE-对照患者额叶皮质上游的生物学调节模块（MAPKAPK3 激活；DGKG、LY96、TNFRSF11B 抑制）和下游（ATP6V0E1、CFB、DGKG、MX1、TGFBR3 激活；LGALS3BP、RASGRP3、RDX、STAT1 抑制），而在 HIVE 的上游（BST2、CFB、LCAT、TNFRSF11B 激活；CFHR1、LY96 抑制）和下游（GAS1、LCAT、LGALS3BP、NFAT5、VEZF1、ZNF652 激活；DGKG、IFITM1、LY96、TNFRSF11B 抑制）。重要的是，我们的数据挖掘表明，HIVE 的 CREB5 调节簇参与了炎症反应、蛋白水解、生物粘附和生物过程的负调节（仅在 HIVE 术语中），而不参与细胞过程、磷酸转移酶、激酶、翻译后蛋白修饰、ATP 结合、跨膜蛋白、钙离子结合、乙酰化和水解酶活性（仅在 HIVE-对照患者术语中），这种情况对 HIVE 的炎症和认知障碍至关重要。我们的结果表明，HIVE-对照患者和 HIVE 中共同的术语包括生物调节、磷酸蛋白、代谢过程、锌、生物合成过程、细胞器、信号转导、防御反应、膜、分泌、信号肽和糖蛋白，这些术语与炎症和认知障碍更为相关，因此我们推断 HIVE 中更强的 CREB5 调节网络与我们的计算结果一致。这对于 HIVE 的炎症和认知障碍来说，更强的 CREB5 调节功能是必要的。
