Using radial basis function networks and significance testing to select effective siRNA sequences

Although short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells, its gene silencing efficacy varies markedly and there are only a few consistencies among the recently reported design rules/guidelines for selecting siRNA sequences effective for mammalian genes. We propose a method for selecting effective siRNA target sequences by using a radial basis function (RBF) network and statistical significance analysis for a large number of known effective and ineffective siRNAs. The siRNA classification is first carried out by using the RBF network and then the preferred and unpreferred nucleotides for effective siRNAs at individual positions are chosen by significance testing. The gene degradation measure is defined as a score based on the preferred and unpreferred nucleotides. The effectiveness for the proposed method was confirmed by evaluating effective and ineffective siRNAs for the recently reported genes (15 genes, 196 sequences) and comparing the scores thus obtained with those obtained using other scoring methods. Since the score is closely correlated with the degree of gene degradation, it can easily be used for selecting high-potential siRNA candidates. The evaluation results indicate that the proposed method may be applicable for many other genes. It will therefore be useful for selecting siRNA sequences in mammalian genes.     

Batch RNAi selector: a standalone program to predict specific siRNA candidates in batches with enhanced sensitivity

RNA interference (RNAi) is a popular and effective method for silencing gene expression. siRNAs should be gene-specific and effective to achieve specific and potent gene silencing. However, most currently available siRNA design programs are web-based programs that either require each sequence be submitted individually, making large-batch analyses difficult to conduct, or only provide limited options for searching off-target candidates (e.g. NCBI-BLAST). We have developed a stand-alone, enhanced RNAi design program that overcomes these shortcomings. We have implemented WU-BLAST, FASTA and SSEARCH homology searches for siRNA candidates to improve gene specific siRNA selection and to identity siRNA candidates that could lead to off-target gene silencing. We also included many new features such as siRNA score calculation and calculation of siRNA internal stability to help select highly potent siRNAs. This program is freely available for academic and commercial use (), and can be installed and run on any Linux machine. Our program automates the search for siRNAs and the resulting data files including a list of siRNA primers with scores and database search results for each siRNA candidate are stored locally for easy retrieval and inspection when needed.     

RFRCDB-siRNA: improved design of siRNAs by random forest regression model coupled with database searching

Although the observations concerning the factors which influence the siRNA efficacy give clues to the mechanism of RNAi, the quantitative prediction of the siRNA efficacy is still a challenge task. In this paper, we introduced a novel non-linear regression method: random forest regression (RFR), to quantitatively estimate siRNAs efficacy values. Compared with an alternative machine learning regression algorithm, support vector machine regression (SVR) and four other score-based algorithms [A. Reynolds, D. Leake, Q. Boese, S. Scaringe, W.S. Marshall, A. Khvorova, Rational siRNA design for RNA interference, Nat. Biotechnol. 22 (2004) 326-330; K. Ui-Tei, Y. Naito, F. Takahashi, T. Haraguchi, H. Ohki-Hamazaki, A. Juni, R. Ueda, K. Saigo, Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference, Nucleic Acids Res. 32 (2004) 936-948; A.C. Hsieh, R. Bo, J. Manola, F. Vazquez, O. Bare, A. Khvorova, S. Scaringe, W.R. Sellers, A library of siRNA duplexes targeting the phosphoinositide 3-kinase pathway: determinants of gene silencing for use in cell-based screens, Nucleic Acids Res. 32 (2004) 893-901; M. Amarzguioui, H. Prydz, An algorithm for selection of functional siRNA sequences, Biochem. Biophys. Res. Commun. 316 (2004) 1050-1058) our RFR model achieved the best performance of all. A web-server, RFRCDB-siRNA (http://www.bioinf.seu.edu.cn/siRNA/index.htm), has been developed. RFRCDB-siRNA consists of two modules: a siRNA-centric database and a RFR prediction system. RFRCDB-siRNA works as follows: (1) Instead of directly predicting the gene silencing activity of siRNAs, the service takes these siRNAs as queries to search against the siRNA-centric database. The matched sequences with the exceeding the user defined functionality value threshold are kept. (2) The mismatched sequences are then processed into the RFR prediction system for further analysis.     

OptiRNAi, an RNAi design tool

RNA interference (RNAi), a recently developed reverse genetics tool, has many advantages compared to traditional gene knockout methods. Appropriate selection of double stranded RNAs identical to a specific region(s) of the target gene is critical for the successful implementation of this technology. Recently, Elbashir et al. [Methods 26 (2002) 199] has established empirical criteria for siRNA sequence selection that significantly improved the success rate for RNAi attempts. We have developed OptiRNAi, a computational tool, which uses the Elbashir et al. criteria to predict appropriate target sequences for siRNA production. Specificity of these siRNAs for the target of interest can then be assessed by the investigator using the embedded Blast search engine optimized for RNAi design. Thus, OptiRNAi is an efficient and user friendly tool for RNAi design based on criteria that are more stringent than other available tools.     

属性重要性评分方法的改进

研究信息系统的属性重要性评分方法,通过引入敏感系数构建神经网络模型,提出属性重要性评分算法,将信息系统的各条件属性和决策属性构造一个径向基函数(RBF)神经网络。经训练和学习后,综合考虑各属性间的关系,动态调整RBF网络的拓扑结构,评分各属性的重要性。以红籽西瓜性状数据作为样本数据和测试数据进行实例分析,验证该方法的有效性。     

Gene expression and protein–protein interaction data for identification of colon cancer related genes using <Emphasis Type="Italic">f</Emphasis>-information measures

One of the most important and challenging problems in functional genomics is how to select the disease genes. In this regard, the paper presents a new computational method to identify disease genes. It judiciously integrates the information of gene expression profiles and shortest path analysis of protein–protein interaction networks. While the \(f\)-information based maximum relevance-maximum significance framework is used to select differentially expressed genes as disease genes using gene expression profiles, the functional protein association network is used to study the mechanism of diseases. An important finding is that some \(f\)-information measures are shown to be effective for selecting relevant and significant genes from microarray data. Extensive experimental study on colorectal cancer establishes the fact that the genes identified by the integrated method have more colorectal cancer genes than the genes identified from the gene expression profiles alone, irrespective of any gene selection algorithm. Also, these genes have greater functional similarity with the reported colorectal cancer genes than the genes identified from the gene expression profiles alone. The enrichment analysis of the obtained genes reveals to be associated with some of the important KEGG pathways. All these results indicate that the integrated method is quite promising and may become a useful tool for identifying disease genes.     

基于OLS算法的RBF网设计方法与实现

在RBF网络学习中用随机数据点作为径向基函数中心,计算神经网络的权,这样的结果往往会造成网络过大或者结果不理想,从而无法满足要求。径向基函数中心的选择基于正交最小二乘法,逐个找出径向基函数的中心,构建出良好的网络。该算法选择的中心最大值不会产生数字的病态问题。正交最小二乘法策略简单、有效,设计的径向基函数网络效果很好。     

用RBF神经网络建立石墨化炉过程模型

研究用RBF神经网络建立石墨化炉过程模型,提出了RBF网络中心点选取方法,所建立的模型精度满足现场要求。     

A People-Counting System Using a Hybrid RBF Neural Network

A people-counting system using hybrid RBF neural network is described. The proposed system is effective and flexible for the purpose of performing on-line people counting. Compared with other conventional approach, this system introduces a novel method for feature extraction. In this Letter, a new type of hybrid RBF network is developed to enhance the classification performance. The hybrid RBF based people-counting system is thoroughly compared with other approaches. Extensive and promising results were obtained and the analysis indicates that the proposed hybrid RBF based system provides excellent people-counting results in an open passage. A supervised clustering method is proposed for initialising the hybrid RBF network. In order to substantiate the introduction of the hybrid RBF and the proposed supervised clustering algorithm, test results on a vowel recognition benchmark dataset are also included in the Letter.     

基于RBF神经网络和小波包的电动机故障诊断研究

针对传统的电动机故障诊断存在很难准确提取故障时的特征信号及对故障作出准确预测的问题,提出了一种基于RBF神经网络和小波包的电动机故障诊断的方法。该方法采用小波包分析技术提取电动机典型轴承故障、转子故障和绝缘故障振动信号的特征频段能量并组成向量作为RBF神经网络的输入,用于诊断电动机的故障。实验和仿真结果表明,使用RBF神经网络对电动机故障诊断是非常有效的,对电动机早期故障的发现及维修有积极意义。     

基于径向基神经网络的电涡流传感器输出特性拟合研究

针对电涡流传感器的输出特性参数非线性较大,不能精确地反映被测物理量的问题,提出了一种采用径向基神经网络对电涡流传感器的输出特性参数进行拟合的方案。该方案采用newrb函数创建一个径向基神经网络,以被测物理量作为输入矩阵、电涡流传感器输出电压作为输出矩阵,对该径向基神经网络进行训练,从而可得到均方根误差小且光滑的电涡流传感器输出特性拟合曲线。实验结果表明,只要选择合适的创建函数和扩展系数,径向基神经网络能有效地实现电涡流传感器输出特性的拟合。     

基于因果关系挖掘的概率基因调控网络的构建

科学的基因聚类方法是构建基因调控网络的前提,但仅以聚类作为构建网络的主要手段只能找到共同调控的基因,不能精确反映基因之间的相互作用过程。贝叶斯网络模型通过基于图的方式求得多变量之间条件独立的概率因果关系,但因其计算复杂性受到应用层面的限制。该文综合考虑几方面因素,在对基因进行聚类基础上,通过对调控关系的预测获得对目标基因的调控基因组,再利用LCD(local causal relation discovery)方法通过限制搜索条件发现基因间的独立关系,进而获得基因调控网络。实验结果表明了该方法的可行性和有效性。     

Classification of binary document images into textual or nontextual data blocks using neural network models

This paper describes a new method for the classification of binary document images as textual or nontextual data blocks using neural network models. Binary document images are first segmented into blocks by the constrained run-length algorithm (CRLA). The component-labeling procedure is used to label the resulting blocks. The features for each block, calculated from the coordinates of its extremities, are then fed into the input layer of a neural network for classification. Four neural networks were considered, and they include back propagation (BP), radial basis functions (RBF), probabilistic neural network (PNN), and Kohonen's self-organizing feature maps (SOFMs). The performance and behavior of these neural network models are analyzed and compared in terms of training times, memory requirements, and classification accuracy. The experiments carried out on a variety of medical journals show the feasibility of using the neural network approach for textual block classification and indicate that in terms of both accuracy and training time RBF should be preferred.     

丁二酸发酵过程的软测量建模研究

生物转化法生产丁二酸的间歇厌氧发酵过程存在明显的不确定性和高度非线性,其中某些参数(如丁二酸浓度)难以在线检测,给过程优化策略的有效实施带来了障碍.最小二乘支持向量机(LS-SVM)是标准支持向量机(SVM)的一种扩展,遵循结构风险最小化原则.将该算法用于丁二酸发酵过程建模.用具有RBF核函数的LS-SVM建立丁二酸浓度的模型,并通过MATLAB 7.0开发工具和径向基(RBF)人工神经网络的建模方法进行比较.结果表明LS-SVM方法比基于RBF神经网络的软测量建模方法降低了83.7%的外推误差,具有更好的泛化能力,使针对丁二酸浓度的在线预估与优化控制成为可能.     

Selecting radial basis function network centers with recursiveorthogonal least squares training

Recursive orthogonal least squares (ROLS) is a numerically robust method for solving for the output layer weights of a radial basis function (RBF) network, and requires less computer memory than the batch alternative. In the paper, the use of ROLS is extended to selecting the centers of an RBF network. It is shown that the information available in an ROLS algorithm after network training can be used to sequentially select centers to minimize the network output error. This provides efficient methods for network reduction to achieve smaller architectures with acceptable accuracy and without retraining. Two selection methods are developed, forward and backward. The methods are illustrated in applications of RBF networks to modeling a nonlinear time series and a real multiinput-multioutput chemical process. The final network models obtained achieve acceptable accuracy with significant reductions in the number of required centers.     

基于RBF和优化Wiener模型的轴承剩余寿命预测

针对滚动轴承寿命准确预测缺乏表征其健康状态的可靠退化指标的问题,提出径向基(RBF)神经网络及带有漂移参数的维纳(Wiener)模型进行剩余寿命预测。首先,使用小波包奇异谱熵提取轴承振动信号初始特征;其次,利用早期无故障样本特征和失效样本特征训练RBF神经网络模型,将已提取特征全寿命数据输入到RBF神经网络模型,计算隶属度,作为轴承退化指标;最后,根据滚动轴承的退化轨迹,选择不同Wiener模型进行退化建模,根据AIC信息准则和对数似然值选择合适的模型,利用极大化轮廓似然函数在线更新模型参数,预测轴承寿命。结果表明,所提出的轴承退化指标能够表征健康状态,基于该退化指标的Wiener模型能够准确预测轴承的剩余寿命。     

改进的RBFNN在运动员竞技状态预测中的应用

提出了一种改进的径向基函数(RBF)神经网络,该神经网络以模糊系统模型为基础。首先利用减法聚类算法确定径向基函数的中心数,然后通过模糊C均值聚类算法优化基函数中心与宽度,最后依据样本数据的聚类结果设计RBF神经网络并进行训练。将该神经网络应用于网球队运动员的竞技状态的预测。仿真结果表明:该算法先进有效、具有较高的精度,用其建立的模型具有较强的实用性。     

Detection of unusual RNA folding regions in HIV and SIV sequences

We have developed a method for detecting more stable and significant folding regions relative to others in the sequence. The algorithm is based on the calculation of the lowest free energy of RNA secondary structures and Monte Carlo simulation. For any given RNA segment, the stability and statistical significance of RNA folding are assessed by two measures: the stability score and the significance score. The stability score measures the degree of thermodynamic stability of the segment between all possible biological segments in the RNA sequence. The significance score characterizes the specific arrangement of the nucleotides in the segment that could imply a structural role for the sequence information. Using these two measures, we are able to detect a series of distinct folding regions where highly stable and statistically significant secondary structures occur in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) sequences.     

基于信息强度的RBF神经网络结构设计研究

在系统研究前馈神经网络的基础上,针对径向基函数(Radial basis function, RBF) 网络的结构设计问题,提出一种弹性RBF神经网络结构优化设计方法. 利用隐含层神经元的输出信息(Output-information, OI)以及隐含层神经元与输出层神经元间的交互信息(Multi-information, MI)分析网络的连接强度, 以此判断增加或删除RBF神经网络隐含层神经元, 同时调整神经网络的拓扑结构,有效地解决了RBF神经网络结构设计问题; 利用梯度下降的参数修正算法保证了最终RBF网络的精度, 实现了神经网络的结构和参数自校正. 通过对典型非线性函数的逼近与污水处理过程关键水质参数建模, 结果证明了该弹性RBF具有良好的动态特征响应能力和逼近能力, 尤其是在训练速度、泛化能力、最终网络结构等方面较之最小资源神经网络(Minimal resource allocation net works, MRAN)、增长修剪RBF 神经网络(Generalized growing and pruning RBF, GGAP-RBF)和自组织RBF神经网络(Self-organizing RBF, SORBF)有较大的提高.     

RBF神经网络在刀具状态监控中的应用研究

提出了一种用RBF神经网络模型监控刀具状态的方法,并以实例验证了RBF网络的有效性。