Efficiently predicting large-scale protein-protein interactions using MapReduce

With a rapid development of high-throughput genomic technologies, a vast amount of protein-protein interactions (PPIs) data has been generated for difference species. However, such set of PPIs is rather small when compared with all possible PPIs. Hence, there is a necessity to specifically develop computational algorithms for large-scale PPI prediction. In response to this need, we propose a parallel algorithm, namely pVLASPD, to perform the prediction task in a distributed manner. In particular, pVLASPD was modified based on the VLASPD algorithm for the purpose of improving the efficiency of VLASPD while maintaining a comparable effectiveness. To do so, we first analyzed VLASPD step by step to identify the places that caused the bottlenecks of efficiency. After that, pVLASPD was developed by parallelizing those inefficient places with the framework of MapReduce. The extensive experimental results demonstrate the promising performance of pVLASPD when applied to prediction of large-scale PPIs.     

基于GO的酵母膜系统蛋白相互作用规律研究

引进描述蛋白质相互作用倾向性参数(PIRB),基于GO(Gene Ontology)和相关的数据库中蛋白质功能注释,对酿酒酵母部分膜蛋白相互作用规律进行了研究,构建了基于PIRB的蛋白质相互作用网络图.结果表明各类膜蛋白质之间的相互作用具有明显的偏向性.对这种偏向性的生物学含义作了简要探讨.     

Identifying changed protein-protein interactions in biological processes by gene coexpression analysis

The interaction strength between 2 proteins is not constant but variable under different conditions. For a given biological process, identification of protein-protein interactions (PPIs) undergoing dynamic change in interaction strength is highly valuable but never achieved before. In this work, we presented a computational approach to identify changed PPIs (cPPIs) on a global scale by analyzing the coexpression level of genes encoding the interacting protein pairs. This approach stemmed from the biological...     

订书肽的合成与应用

许多重要的生物过程的调节都通过蛋白-蛋白相互作用来实现的。一般,蛋白-蛋白作用的界面太大而不能被小分子药物选择性靶向,因此小分子药物很难高效特异性地阻断该类型的相互作用。此外,由于蛋白质药物很难透过细胞膜,它们也不能直接靶向细胞内的相互作用。由于当前药物分子的限制,发展下一代既能进入细胞膜又能特异性靶向蛋白-蛋白相互作用的分子成为新的研究热点。为了克服上述药物分子的缺点,Verdine等发展了一种全碳支架的具有α-螺旋结构的新型多肽,这种多肽被称作订书肽（stapled peptides）。相比于天然多肽,订书肽有更高的酶解稳定性并且可以进入细胞膜,从而提高了它的药理性能。本文将从订书肽的化学合成、生物物理性能的表征和其在癌症和HIV治疗、信号通路的调节和肿瘤激活蛋白的抑制方面的生物应用详细介绍订书肽的最新进展。     

四磨汤治疗功能性胃肠病机制的网络药理学分析

目的构建四磨汤活性成分-作用靶点网络和蛋白相互作用网络,富集靶点信号通路,探讨其治疗功能性胃肠病的作用机制。方法以四磨汤中槟榔次碱、槟榔碱、去甲槟榔次碱、去甲槟榔碱、木香烃内酯、去氢木香内酯等22个活性成分为研究对象,运用TCMSP及BATMAN-TCM数据库以及Pharm Mapper反向分子对接服务器预测四磨汤活性成分对应的靶点,将其与GeneCards、DisGeNET、OpenTargets、CTD数据库中功能性胃肠病靶点进行比对找重,采用Cytoscape 3.5.1软件构建活性成分-靶点网络,STRING平台构建靶蛋白互作网络,借助DAVID平台对靶点KEGG通路进行分析。结果 22个四磨汤活性成分作用的190个靶点,主要富集在神经-递质相关的5-羟色胺能突触、多巴胺能突触;平滑肌运动相关的钙信号通路、c AMP信号通路;以及炎症相关的TNF信号通路、NF-κB信号通路等17条信号通路。结论四磨汤治疗功能性胃肠病的主要机制在于其多成分、多靶点调控胃肠神经传导、平滑肌运动以及炎症。     

Human nectin-like 1, a novel membrane protein interacting with protein 4.1 R

Human nectin-like 1 (NECL1) full-length cDNA was cloned by bioinformatics method when searching for candidate membrane proteins interacting with members of protein 4.1 family. The cytoplasmic and extracellular regions of NECL1 were expressed in and purified from E. coli, and the polyclonal antibody was produced. Interaction between the cytoplasmic region of NECL1 and the 30 kD membrane binding domain of protein 4.1 on red blood cell (4. 1R) was demonstrated by IAsys-biosensor system and GST pull-down experiment. Results of biotin-labeled peptide ELISA further demonstrated the key amino acids for the binding. The interaction research of NECL1's cytoplasmic domain provides basis for further study of the functions of NECL1 in nervous system.     

德国小蠊致敏原Bla g 2的Glu 233突变的分子对接研究

为探讨Bla g 2的E233A突变对抗原抗体相互作用的影响,从RCSB数据库下载德国小蠊致敏原Bla g 2野生型及其单克隆抗体4C3的NMR结构,运用Swiss PDB Viewer将Bla g 2野生型(E233-93Q)构建为突变型(E233A-93Q)三维结构;并将Bla g 2野生型和突变型分别与其单克隆抗体4C3进行分子动力学模拟和蛋白-蛋白对接.结果表明:突变体E233A与单克隆抗体4C3结合能力下降,进而增加了与Ig E的结合力,可能加重过敏反应的发生.     

Regulating Effect of Cytochrome b5 Overexpression on Human Breast Cancer Cells

Imbalance in the cellular redox system is thought to be associated with the induction and progression of breast cancers, and heme proteins may regulate the redox balance. Cytochrome b₅ (Cyt b₅) is a small mitochondrial heme protein. Its function and regulating mechanism in breast cancer remain unknown. In this study, we elucidated the level of endogenous oxidative stress in breast cancer cells, MCF-7 cells (hormone receptor-positive cells) and MDA-MB-231 cells (triple-negative cells), and investigated the difference in Cyt b₅ content. Based on the low content of Cyt b₅ in MDA-MB-231 cells, the overexpression of Cyt b₅ was found to regulate the oxidative stress and apoptosis cascades, including ERK1/2 and Akt signaling pathways. The overexpressed Cyt b₅ MDA-MB-231 cells were shown to exhibit decreased oxidative stress, less phosphorylation of ERK1/2 and Akt, and less cleavage of caspases 3 and 9 upon treatment with H₂O₂, as compared to those of normal MDA-MB-231 cells. Moreover, the overexpressed Cyt b₅ most likely functioned by interacting with its protein partner, Cyt c, as suggested by co-immunoprecipitation studies. These results indicated that Cyt b₅ has different effects on breast cancer cells of different phenotypes, which provides useful information for understanding the multiple roles of Cyt b₅ and provides clues for clinical treatment.     

基于自训练的蛋白质相互作用关系抽取方法

基于有监督机器学习算法的蛋白质相互作用关系抽取方法仍然面临一个问题:标注数据集有限,导致算法无法得到充分学习。该文首先构造了一个丰富的特征空间,包括句法、词汇、词性等特征;然后,该文对不同数据集数据分布的不一致性进行了分析,在此基础上提出了一种基于自训练的数据添加算法,通过不断从未标注数据集中选择置信度高的样本加入到已标注数据集中,扩大数据集规模,提高算法效率。实验结果表明:在5个常用的蛋白质相互作用关系数据集上,该方法均有助于提高抽取性能。     

应用改进的共鸣识别模型预测蛋白质相互作用

蛋白质是所有生命活动的载体,它们之间的相互作用在生命活动中起着至关重要的作用.该文介绍了原有的用于预测蛋白质相互作用的共鸣识别模型,并对该模型运用小波变换进行改进,提出了改进后的共鸣识别模型.该模型的最大特点在于直接通过蛋白质的一级结构预测蛋白质之间的相互作用,改进后的模型较原模型更加适合于蛋白质相互作用的预测.运用改进的共鸣识别模型进行了数值试验,取得了较好的预测效果.