基于临床与基因图谱的结肠癌基因标签提取

由于基因间的调控和相互作用表现为功能基因组合的形式,在对样本的分类能力是以特征集合的形式整体体现出来的.由此,考察由多个基因构成的基因簇作为区分常人和癌症患者的分类因素,利用独立成分分析(ICA)技术最大程度地降低基因之间的相互影响,从而获得基因簇信息.随后采用了支持向量机,依据提取出的基因簇进行分类,筛选出致病的癌症基因.为了能够得到最好的分类因素,将问题转化为稀疏表示的优化问题.此外,还利用含噪声的ICA和带松弛因子的非光滑优化模型来研究含噪声的基因图谱.最后,借助于条件概率模型,将临床结论与基因图谱相结合,对病人数据进行了筛选.     

基于基因表达谱的肿瘤识别与分类特征基因提取研究

针对基因表达谱信息基因提取的问题,使用Wilcoxon秩和检验方法进行"无关基因"的剔除,基于高低水平基因表达的特点,建立了关于高/低表达水平的双线性回归模型,基于残差分析提取了19个特征基因.使用启发式宽度优先搜索算法搜索最优基因子集,确定结肠癌的基因"标签",运用支持向量机对分类效果进行检验,分类效果良好.     

不确定条件下工程项目的多目标模糊均衡优化

在工程项目多目标优化问题研究基础上,研究不确定环境下工程项目多目标均衡优化问题.利用模糊数表示费用变化率和质量变化率,考虑模糊集的不同可能性水平,建立工程项目多目标模糊均衡优化模型,给出模型的求解方法和步骤,得到不同可能性水平下多目标优化问题的最优折衷解变化范围.优化方法使决策者能够根据决策风险的大小进行最优目标值的确定.     

基于SMA模型的扩张型心肌病影响基因分析

医学研究表明约30%的扩张型心肌病与遗传因素有关,因此从基因水平寻找其病因及发病机制越来越引起国内外学者的重视.采用针对超高维数据的序贯模型平均(SMA)方法对扩张型心肌病转基因小鼠微阵列数据建立回归模型,确定哪些基因对小鼠中G蛋白偶联受体的过表达有影响从而导致小鼠的心肌病,结果发现Msa.2877.0,Msa.741.0,Msa.768.0和Msa.2604.0四个基因是影响小鼠扩张型心肌病的主要基因,且SMA对该数据的拟合和预测都明显优于以往常用的SIS,L2boost及Lasso等变量选择方法.研究结果对进一步了解人类心脏病的发病机理有一定的借鉴意义.     

考虑共享不确定因素的应急设施最大覆盖选址模型

为提升应急设施的服务质量和抵御中断风险的能力,研究应急设施最大覆盖选址-分配决策问题。扩展无容量限制的固定费用的可靠性选址决策模型,建立考虑共享不确定因素的应急设施最大覆盖选址优化模型,通过在目标和约束中引入budget不确定集刻画共享不确定因素,基于Bertsimas和Sim鲁棒优化方法建立混合整数规划模型,并将非线性问题转化为易于求解的鲁棒等价模型,利用带混沌搜索策略的改进灰狼优化算法求解模型,并对不确定鲁棒水平和中断概率进行敏感性分析。最后通过案例及数据仿真结果的对比分析,验证了模型的合理性和有效性,并给出最优的选址分配布局。     

基于模糊神经网络建模的RFID室内定位算法

将模糊神经网络FNN应用于基于RFID技术的室内定位系统IPS,提出一种基于模糊神经网络的RFID室内定位算法,算法将参考标签数据作为神经网络的训练样本,建立"标签接收信号强度与标签读写器间距离RSSI-DIST"的映射模型,然后利用最小二乘解确定目标的位置坐标.同时,对比了传统BP神经网络和FNN网络在建模和定位中的性能.在仿真和硬件平台测试中,模糊神经网络都要比BP表现出更优异的性能,表明基于模糊神经网络的算法更适合于IPS系统.     

工期与收益的最优化模型

运用经济学原理及最优决策方案 ,建立了如何选择最优工期和制定奖惩措施的动态优化模型 .利用泛函变分法求出在各种情况下的最优工期 ,并确定出影响最优工期的各种因素 ;然后确定出使双方都有利的激励强度 ;最后利用计算机对模型进行了模拟分析 ,并对结果给出了详细的分析 .     

急性髓细胞白血病基因筛选模型的贝叶斯分析

基因表达数据蕴含着大量的生物信息,在生物基因信息研究中,筛选表达水平发生显著变化的差异基因是认识疾病形成机理和辅助靶点药物研究的关键问题.根据急性髓细胞白血病(AML)的基因表达数据,构造基因均值差序列,建立贝叶斯分层混合模型,并为模型的参数赋予具有基因生物特征的先验信息.采用马尔可夫链蒙特卡洛(MCMC)算法对模型参数进行估计,并筛选出急性髓细胞白血病差异表达基因.在实际数据分析中,从美国生物信息中心(NCBI)的高通量基因表达数据库中获取急性髓细胞白血病基因数据集,从经过非特异滤波预处理的14688个急性髓细胞白血病基因中筛选出711个差异表达基因,差异表达基因数仅占急性髓细胞白血病基因总数的4.84%,这一结果与基因差异表达的生物学原理相吻合.     

组合预测方法在大气环境评价中的应用

李振亮．组合预测方法在大气环境评价中的应用．数理统计与管理，１９９７，１６（４），１２～１５．本文利用组合预测理论和方法，建立了一种大气环境质量评价的组合模型。实例分析表明，该组合评价模型具有利用各单一评价模型提供的信息和集中各单一模型的优点，是一种稳健和优化的环境质量评价模型。     

利用动态贝叶斯网构建基因调控网络的研究进展

构建基因调控网络是21世纪人类科学所面临的重要挑战之一。基因调控网络是一个基因组内基因相互作用而形成的关系网络,它从全基因组水平上以系统和全局的角度来研究复杂的生命现象及其本质。本文阐述了近几年来此领域的研究进展,着重介绍利用动态贝叶斯网络重构基因调控网络的若干模型,包括加权核l1模型,正则化模型、高斯混合贝叶斯网模型和自回归时间变化模型。     

Problems in gene clustering based on gene expression data

In this work, we assess the suitability of cluster analysis for the gene grouping problem confronted with microarray data. Gene clustering is the exercise of grouping genes based on attributes, which are generally the expression levels over a number of conditions or subpopulations. The hope is that similarity with respect to expression is often indicative of similarity with respect to much more fundamental and elusive qualities, such as function. By formally defining the true gene-specific attributes as parameters, such as expected expression across the conditions, we obtain a well-defined gene clustering parameter of interest, which greatly facilitates the statistical treatment of gene clustering. We point out that genome-wide collections of expression trajectories often lack natural clustering structure, prior to ad hoc gene filtering. The gene filters in common use induce a certain circularity to most gene cluster analyses: genes are points in the attribute space, a filter is applied to depopulate certain areas of the space, and then clusters are sought (and often found!) in the “cleaned” attribute space. As a result, statistical investigations of cluster number and clustering strength are just as much a study of the stringency and nature of the filter as they are of any biological gene clusters. In the absence of natural clusters, gene clustering may still be a worthwhile exercise in data segmentation. In this context, partitions can be fruitfully encoded in adjacency matrices and the sampling distribution of such matrices can be studied with a variety of bootstrapping techniques.     

基因调控网络推断研究进展

随着高通量技术的发展,越来越多的生物医学组学数据亟需处理与分析,基于运筹优化的生物信息学方法是有效解析高维生物医学数据的重要途径之一。综述了近年来在基因调控网络推断方面的研究进展。针对不同类型的转录组学数据和研究目的,分别建立了相应的基因调控网络推断方法,主要包括先验基因调控网络数据库的建立、基于条件互信息的因果网络推断、基于微分方程的动态基因调控网络推断、转录调控和转录后调控协同作用的网络推断以及基因调控网络活性评价等,并展望了基因调控网络推断的重要研究方向。     

Game Theory applied to gene expression analysis

This is a summary of the author’s Ph.D. thesis supervised by Fioravante Patrone and Stefano Bonassi and defended on 25 May 2006 at the Università degli Studi di Genova. The thesis in written in English and a copy is available from the author upon request. This work deals with the discussion and the application of a methodology based on Game Theory for the analysis of gene expression data. Nowadays, microarray technology is available for taking “pictures” of gene expressions. Within a single experiment of this sophisticated technology, the level of expression of thousands of genes can be estimated in a sample of cells under given conditions. Roughly speaking, the starting point is the observation of a “picture” of gene expressions in a sample of cells under a biological condition of interest, for example a tumor. Then, Game Theory plays a primary role to quantitatively evaluate the relevance of each gene in regulating or provoking the condition of interest, taking into account the observed relationships in all subgroups of genes.      

基于FCM算法的小脑基因模糊聚类分析

探讨基因表达数据的聚类分析方法,结合一种聚类结果的评判准则,应用于胎儿小脑基因表达数据,得到了最优的聚类结果,并做出了生物学解释.利用Matlab软件进行了仿真,利用模糊聚类Xie-Beni指数得到了最优聚类数,并把每一类对应的基因标号输出到txt文件,最后进行生物学解释.得到的小脑基因最优聚类数为3类,与生物学意义比较吻合,各类中的基因功能接近.基于FCM算法的基因模糊聚类是有效的,结果具有一定生物学意义,能对生物学基因聚类有一定指导作用.     

Finding predictive gene groups from microarray data

Microarray experiments generate large datasets with expression values for thousands of genes, but not more than a few dozens of samples. A challenging task with these data is to reveal groups of genes which act together and whose collective expression is strongly associated with an outcome variable of interest. To find these groups, we suggest the use of supervised algorithms: these are procedures which use external information about the response variable for grouping the genes. We present Pelora, an algorithm based on penalized logistic regression analysis, that combines gene selection, gene grouping and sample classification in a supervised, simultaneous way. With an empirical study on six different microarray datasets, we show that Pelora identifies gene groups whose expression centroids have very good predictive potential and yield results that can keep up with state-of-the-art classification methods based on single genes. Thus, our gene groups can be beneficial in medical diagnostics and prognostics, but they may also provide more biological insights into gene function and regulation.     

Singular perturbation analysis and gene regulatory networks with delay

The problem of how the dynamics of the smooth gene networks is related to the simplified dynamics of the Boolean networks is studied. The emphasis is put on the gene regulatory networks with delay. Asymptotic analysis which is applied in the paper goes back to Tikhonov’s theory of singular perturbed differential equations and a modified algorithm of reducing delay equations to ordinary differential equations. A number of illustrative examples complements the theory which is offered in the paper.     

An optimization approach to gene stacking

We present a multi-objective integer programming model for the gene stacking problem, which is to bring desirable alleles found in multiple inbred lines to a single target genotype. Pareto optimal solutions from the model provide strategic stacking schemes to maximize the likelihood of successfully creating the target genotypes and to minimize the number of generations associated with a stacking strategy. A consideration of genetic diversity is also incorporated in the models to preserve all desirable allelic variants in the target population. Although the gene stacking problem is proved to be NP-hard, we have been able to obtain Pareto frontiers for smaller sized instances within one minute using the state-of-the-art commercial computer solvers in our computational experiments.     

Sparse graphical models for exploring gene expression data

We discuss the theoretical structure and constructive methodology for large-scale graphical models, motivated by their potential in evaluating and aiding the exploration of patterns of association in gene expression data. The theoretical discussion covers basic ideas and connections between Gaussian graphical models, dependency networks and specific classes of directed acyclic graphs we refer to as compositional networks. We describe a constructive approach to generating interesting graphical models for very high-dimensional distributions that builds on the relationships between these various stylized graphical representations. Issues of consistency of models and priors across dimension are key. The resulting methods are of value in evaluating patterns of association in large-scale gene expression data with a view to generating biological insights about genes related to a known molecular pathway or set of specified genes. Some initial examples relate to the estrogen receptor pathway in breast cancer, and the Rb-E2F cell proliferation control pathway.     

On some multidimensional models of gene network functioning

We obtain some sufficient conditions for the nonuniqueness of cycles in nonlinear dynamical systems considered as the models of gene network functioning. The constructive methods for the determination of these cycles and the invariant surfaces containing the mare described as well.