基于模体中心结构的蛋白质复合物识别算法

基于蛋白质相互作用的网络有明显模块化特征, 其对预测蛋白质功能、解释特定的生物进程具有重要作用, 网络模体是复杂网络演化的 重要拓扑结构, 其代表了复杂系统中的重要功能单元, 具有进化保守性的特性, 提出一种新的基于网络模体为核心节点组的蛋白质复合物识别算法. 该算法根据蛋白质相互作用网络的拓扑特性, 将模体作为蛋白质复合物的中心结构体, 并基于中心结构体进行二层节点扩充, 能准确有效地识别蛋白质复合物. 并且将复合物二维网络进行三维转化, 从而更直观清晰地展示复合物的结构体特征. 实验结果验证了该算法的有效性及可行性.     

基于极大团扩展的蛋白质复合物识别算法

针对蛋白质复合物识别工具CFinder容易识别出超大复合物的缺陷,提出一种基于极大团扩展的蛋白质复合物识别算法(IPC-MCE)。将极大团看作蛋白质复合物的核,通过考查核的邻居顶点与核内顶点的作用概率决定邻居顶点是否属于该复合物。基于酵母蛋白质相互作用网络平台的实验结果表明:与CFinder相比,提出的IPC-MCE算法在相同条件下能够更精确地标识已知蛋白质复合物;在最优参数设置下,IPC-MCE算法标识的已知蛋白质复合物数量是CFinder标识数量的2倍多,说明IPC-MCE算法具有更强的蛋白质复合物识别能力。     

基于复合物信息和亚细胞定位信息的关键蛋白质识别

针对蛋白质相互作用(protein-protein interaction,PPI)网络中存在大量噪声,以及现有关键蛋白识别方法的挖掘效率和预测准确率不高等问题,提出一种基于复合物信息和亚细胞定位信息(united protein complexes and subcellular locallizations,PCSL)来识别关键蛋白质。首先,整合PPI网络的拓扑属性、生物属性和空间属性构建加权网络,以降低PPI网络中噪声的影响,达到提升PPI网络的可靠性的目的;其次,根据复合物信息和空间信息,设计一种衡量蛋白质关键性的度量,从多维角度强化关键蛋白质在PPI中的重要程度;最后,利用基于PPI网络拓扑特性的寻优算法,设计一种新的试探策略,提升挖掘关键蛋白质的效率。PCSL方法应用在DIP(database of interacting protein)数据集上进行验证。实验结果表明,与其他10种关键蛋白质识别方法相比较,该方法具有较好的识别性能,能够识别更多的关键蛋白质。     

基于复合物结构和网络拓扑特性的关键蛋白质识别算法

关键蛋白质的识别有助于从分子水平上理解生命的活动过程,然而仅从拓扑特性角度来识别的关键蛋白质不够精准,因此为了提高识别准确率,结合复合物信息提出了确定蛋白质关键性的指标模型EIC,该模型是基于蛋白质复合物内的局部中心性特性以及网络的全局信息特性来考虑.使用DIP和MIPS两种蛋白质相互作用(PPI)网络作为实验数据集,...     

水稻蛋白质相互作用网络的预测与分析

通过同源映射的方法,利用6个模式物种的蛋白质相互作用数据预测水稻的蛋白质相互作用网络.预测到水稻中有4483个蛋白质参与了24942个蛋白质相互作用.通过GO注释,结构域相互作用,基因共表达等3个证据评估预测网络的质量,并对网络进行了拓扑属性分析.结果表明水稻的蛋白质相互作用网络符合scale-free属性.通过对网络中功能模块的分析,可以预测蛋白质的功能和亚细胞定位信息.     

蛋白质功能预测的蚁群优化算法

预测蛋白质功能是后基因组时代最具挑战性的问题之一,在大规模数据下采用高性能的功能预测算法能够节省大量的实验时间和成本.利用基于蛋白质相互作用网络的全局优化模型,提出了蛋白质功能预测的蚁群优化算法,算法在考虑全局模型的同时还利用了网络的先验信息,提高了搜索效率,仿真结果表明,蚁群优化算法能够有效对蛋白质功能进行预测,并且对蛋白质相互作用网络中的假阳性、假阴性数据具有较高的容错能力.     

一种改良的蛋白质复合物识别方法

高通量的方法产生了大量蛋白质相互作用数据.然而研究表明,对于已过滤的双杂交酵母数据集,假阳性相互作用的比例达到50%左右.这些假阳性这对于进一步的PPI网络研究带来了负面影响.因此,消除假阳性或者降低假阳性带来的负面影响变得非常重要.根据蛋白质相互作用网络的拓扑特性,每一组相互作用被赋予一个存在概率,概率值表示相互作用的可靠程度,概率值为0的相互作用被标识为假阳性予以消除.提出了一种改良的蛋白质复合物识别方法,该方法基于核-附件的思想,识别的复合物具有更强的生物统计特性.改良的新方法及其他经典的识别方法在酵母数据集上得到运行,实验结果表明,改良的方法性能优于现有的经典方法.     

一种融合多组学数据的关键蛋白质预测算法

关键蛋白质在维持生物体的生理活动中发挥着重要的作用，预测关键蛋白质有助于设计药物分子靶标.随着高通量技术的发展，基于蛋白质相互作用关系数据采用计算方法识别关键蛋白质成为当前的热门研究.研究表明，将蛋白质相互作用网络与其他生物学信息结合起来能够更有效地识别关键蛋白质.因此，本研究提出一种整合蛋白质相互作用数据、基因本体注释信息、蛋白质亚细胞定位信息及蛋白质结构域信息的识别关键蛋白质的新方法TGSD.为了评估新算法的有效性，选取4组常用的酵母测试数据集进行仿真实验，详细比较TGSD方法与其他7种经典方法的识别效果.数值结果显示，TGSD在预测正确关键蛋白质数目和准确率等统计指标上明显优于其他算法.     

基于最短路径的关键蛋白质识别研究

关键蛋白质的识别有助于从系统水平上理解生命活动过程,基于蛋白质相互作用网络拓扑特征的关键蛋白质识别可以有效地提高识别精度和速度.通过蛋白质节点的最短路径数和点介数可以作为衡量其节点中心度的方法,但计算速度和计算规模有限.根据所预测蛋白质相互作用网络的特点,提出了基于最短路径技术的关键蛋白质识别方法,选择合理的识别阈值和...     

Comparing the biological coherence of network clusters identified by different detection algorithms

Protein-protein interaction networks serve to carry out basic molecular activity in the cell. Detecting the modular structures from the protein-protein interaction network is important for understanding the organization, function and dynamics of a biological system. In order to identify functional neighbor- hoods based on network topology, many network cluster identification algorithms have been devel- oped. However, each algorithm might dissect a network from a different aspect and may provide dif- ferent insight on the network partition. In order to objectively evaluate the performance of four com- monly used cluster detection algorithms: molecular complex detection (MCODE), NetworkBlast, shortest-distance clustering (SDC) and Girvan-Newman (G-N) algorithm, we compared the biological coherence of the network clusters found by these algorithms through a uniform evaluation framework. Each algorithm was utilized to find network clusters in two different protein-protein interaction net- works with various parameters. Comparison of the resulting network clusters indicates that clusters found by MCODE and SDC are of higher biological coherence than those by NetworkBlast and G-N algorithm.     

Co-regulated Protein Functional Modules with Varying Activities in Dynamic PPI Networks

Current methods for the detection of differential gene expression focus on finding individual genes that may be responsible for certain diseases or external irritants. However, for common genetic diseases, multiple genes and their interactions should be understood and treated together during the exploration of disease causes and possible drug design. The present study focuses on analyzing the dynamic patterns of co-regulated modules during biological progression and determining those having remarkably varying activities, using the yeast cell cycle as a case study. We first constructed dynamic active protein-protein interaction networks by modeling the activity of proteins and assembling the dynamic co-regulation protein network at each time point. The dynamic active modules were detected using a method based on the Bayesian graphical model and then the modules with the most varied dispersion of clustering coefficients, which could be responsible for the dynamic mechanism of the cell cycle, were identified. Comparison of results from our functional module detection with the state-of-art functional module detection methods and validation of the ranking of activities of functional modules using GO annotations demonstrate the efficacy of our method for narrowing the scope of possible essential responding modules that could provide multiple targets for biologists to further experimentally validate.     

基于序列剖面和可及表面积的蛋白质相互作用位点的预测

蛋白质相互作用位点的预测对于突变设计和蛋白质相互作用网络的重构都是至关重要的.由于实验确定的蛋白质复合物和蛋白质配体复合物的结构依然相当少,预测蛋白质相互作用位点的计算方法就显得十分重要.该文提出了一种以支持向量机为分类器,以邻近残基的序列剖面和可及表面积为输入数据来预测蛋白质相互作用位点的方法.计算结果显示,界面残基和非界面残基被识别的准确率为75.12%,假阳性率为28.04%.与输入数据仅有序列剖面的方法相比,界面残基和非界面残基被识别的准确率提高了4.34%,假阳性率降低了4.63%.     

多粒度PPI网络描述模型及其蚁群优化的功能模块检测方法

针对蚁群算法在大规模蛋白质相互作用(protein-protein interaction,PPI)网络中进行功能模块检测所暴露的时间性能方面的不足,提出了一种基于多粒度描述和蚁群优化的快速求解算法。首先,从粒度计算的角度,给出了一种新的多粒度PPI网络描述模型;然后,基于该模型,设计了融合功能和结构信息的粒度划分,粗粒度的蚁群寻优,解的还原与优化3个阶段的求解过程。在大规模PPI网络上的实验表明:算法在保证检测质量的同时,能显著降低利用蚁群算法进行功能模块检测的求解时间,而且与近年来的一些经典算法相比在检测精度上也具有一定的优势。     

Analysis of correlations between protein complex and protein-protein interaction and mRNA expression

Protein-protein interaction is a physical interaction of two proteins in living cells. In budding yeast Saccharomyces cerevisiae, large-seale protein-protein interaction data have been obtained through high-throughput yeast two-hybrid systems (Y2H) and protein complex purification techniques based on mass-spectrometry. Here, we collect 11855 interactions between total 2617 proteins. Through seriate genome-wide mRNA expression data, similarity between two genes could be measured. Protein complex data can also be obtained publicly and can be translated to pair relationship that any two proteins can only exist in the same complex or not. Analysis of protein complex data, protein-protein interaction data and mRNA expression data can elucidate correlations between them. The results show that proteins that have interactions or similar expression patterns have a higher possibility to be in the same protein complex than randomized selected proteins, and proteins which have interactions and similar expression patterns are even more possible to exist in the same protein complex. The work indirates that comprehensive integration and analysis of public large-seale bioinformatical data, such as protein complex data, protein-protein interaction data and mRNA expression data, may help to uncover their relationships and common biological information underlying these data. The strategies described here may help to integrate and analyze other functional genomic and proteomic data, such as gene expression profiling, protein-localization mapping and large-scale phenotypic data, both in yeast and in other organisms.     

Discovering protein complexes from protein-protein interaction data by dense subgraph

High-throughput techniques,such as the yeast-two-hybrid system,produce mass protein-protein interaction data. The new technique makes it possible to predict protein complexes by com-putation. A novel method,named DSDA,has been put forward to predict protein complexes via dense subgraph because the proteins among a protein complex have a much tighter relation among them than with others. This method chooses a node with its neighbors to form the initial subgraph,and chooses a node which has the tightest relation with the subgraph according to greedy strategy,then the chosen node is added into the initial subgraph until the subgraph density is below the threshold value. The ob-tained subgraph is then removed from the network and the process continues until no subgraph can be detected. Compared with other algorithms,DSDA can predict not only non-overlap protein com-plexes but also overlap protein complexes. The experiment results show that DSDA predict as many protein complexes as possible. And in Y78K network the accuracy of DSDA is as twice times as that of RNSC and MCL.     

基于混合核函数SVM的蛋白质相互作用预测方法

针对蛋白质相互作用的预测问题,提出一种以余弦核和线性差值累加核为基核的对偶混合核函数SVM的蛋白质相互作用预测方法.该方法充分考虑了蛋白质的结构域特征,同时根据蛋白质相互作用数据应具有顺序无关的特点,将"对偶"思想引入SVM核函数中.对两个真实的蛋白质相互作用数据集Yeast PPI和Human PPI的测试结果表明,提出的方法与其它方法相比能够有效地提高蛋白质相互作用预测的准确率.     

Finding finer functions for partially characterized proteins by protein-protein interaction networks

Based on high-throughput data, numerous algorithms have been designed to find functions of novel proteins. However, the effectiveness of such algorithms is currently limited by some fundamental factors, including (1) the low a-priori probability of novel proteins participating in a detailed function; (2) the huge false data present in high-throughput datasets; (3) the incomplete data coverage of functional classes; (4) the abundant but heterogeneous negative samples for training the algorithms; and (5) the lack of detailed functional knowledge for training algorithms. Here, for partially characterized proteins, we suggest an approach to finding their finer functions based on protein interaction sub-networks or gene expression patterns, defined in function-specific subspaces. The proposed approach can lessen the above-mentioned problems by properly defining the prediction range and functionally filtering the noisy data, and thus can efficiently find proteins’ novel functions. For thousands of yeast and human proteins partially characterized, it is able to reliably find their finer functions (e.g., the translational functions) with more than 90% precision. The predicted finer functions are highly valuable both for guiding the follow-up wet-lab validation and for providing the necessary data for training algorithms to learn other proteins.     

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.