总体平均处理效应的拟极大似然估计

本文给出可交换条件下多维协变量的带有测量误差的多维结构回归模型,利用该模型研究总体平均处理效应的估计,给出当暴露组和对照组的协变量测量误差同分布时总体平均处理效应的拟极大似然估计及其性质．     

最大似然法和贝叶斯推论与似然比检验探讨泽泻目系统发育关系

应用最大似然法(ML)、贝叶斯推论(BI)、邻接法(NJ)和似然比检验(hLRTs)进行泽泻目分子系统学研究。所用的rbcL基因序列代表了泽泻目14科46属以及作为外类群的6相关属。研究结果表明,*等级制似然比检验表明泽泻目rbcL序列最适合的DNA进化模型为GTR+I+G,最大似然法、贝叶斯法和邻接法构建的系统发育树拓扑结构相似,没有显著的差异,但贝叶斯树支持率较高;泽泻目为一单系类群,由两个主要谱系分支构成,深层分布格局由5个主要分支构成。基于分子系统发育树,文中对泽泻目科间、水鳖科+茨藻科、泽泻科+花蔺科+黄花蔺科、和\"Cymodoeaceae complex\"的系统发育关系进行了讨论。研究结果还表明,泽泻目系统发育关系可能还需要更多的证据进一步的澄清。     

非线性再生散度随机效应模型的极大似然估计及随机逼近算法

非线性再生散度随机效应模型包括了非线性随机效应模型和指数族非线性随机效应模型等．通过视模型中的随机效应为假想的缺失数据和应用Metropolis-Hastings(简称MH) 算法,提出了模型参数极大似然估计的随机逼近算法．模拟研究和实例分析表明了该算法的可行性．     

非线性再生散度随机效应模型的极大似然估计及EM算法

非线性再生散度随机效应模型是指数族非线性随机效应模型和非线性再生散度模型的推广和发展．通过视模型中的随机效应为假想的缺失数据和应用Metropolis-Hastings（MH）算法,提出了模型参数极大似然估计的Monte-Carlo EM（MCEM）算法,并用模拟研究和实例分析说明了该算法的可行性．     

远交群体动态性状基因定位的似然分析Ⅰ.理论方法

受动物遗传育种中用来估计动态性状育种值的随机回归测定日模型思想的启发 ,将关于时间 (测定日期 )的Legendre多项式镶嵌在遗传模型的每个遗传效应中 ,以刻画QTL对动态性状变化过程的作用 ,从而建立起动态性状基因定位的数学模型。利用远交设计群体 ,阐述了动态性状基因定位的似然分析原理 ,推导了定位参数似然估计的EM法两步求解过程。结合动态性状遗传分析的特点和普通数量性状基因定位研究进展 ,还提出了有关动态性状基因定位进一步研究的设想     

突变积累实验中极大似然法和距法的比较

最近,人们突变积累实验（MA）中测定有害基因突变（DGM）的兴趣大增。在MA实验中有两种常见的DGM估计方法（极大似然法ML和距法MM）,依靠计算机模拟和处理真实数据的应用软件来比较这两种方法。结论是：ML法难于得到最大似然估计（MLEs),所以ML法不如MM法估计有效;即使MLEs可得,也因其具严重的微样误差（据偏差和抽样差异）而产生估计偏差;似然函数曲线较平坦而难于区分高峰态和低峰态的分布。     

在雌不发生交换的鳞翅目类昆虫中使用F2群体作图显隐性分子标记连锁图谱的极大似然(ML)法

在鳞坡目昆虫中,雌性个体的减数分裂细胞不发生遗传重组。这类物种的杂效Ｆ２群体中杂合子基因型的与一般物种中雌雄个体的减数分裂细胞都发生遗传重组的Ｆ２群体杂合子表型不同,由于这个原因,作用这类物种的遗传连锁图谱通常中使用回交群体。但是,用回效群体傻所得的图谱是不完整的,因为图谱上所有的标记都是百轮回亲本提供的,因此 不会超过杂交Ｆ２各体的一半。另外,目前还没有任何方法和软件可以用杂效Ｆ２群体来作图鳞翅     

删失数据下非线性半参数回归模型中参数的经验似然推断

考察了响应变量在随机删失情形下的非线性半参数回归模型,构造了未知参数的经验对数似然比统计量和调整经验对数似然比统计量,证明在一定条件下,所构造的经验似然比统计量渐近于X~2分布,并由此构造出未知参数的置信域.此外,又构造了未知参数的最小二乘估计量,证明了它的渐近性质.通过模拟研究表明,经验似然方法在置信域的覆盖概率以及精度方面要优于最小二乘法.     

基于线粒体基因组全序列的鲟形目鱼类(Pisces: Acipenseriformes)的分子系统发育重建

为厘清鲟形目鱼类的系统发育, 研究新测定了中华鲟(Acipenser sinensis)、长江鲟(A. dabryanus)、短吻鲟(A. brevirostrum)、纳氏鲟(A. naccarii)、鳇(Huso dauricus)和匙吻鲟(Polyodon spathula)共6种鲟类的线粒体全基因组序列。联合已测的17种鲟类的线粒体基因组数据, 利用最大似然法和贝叶斯法重建了鲟形目鱼类的分子系统发育关系, 并采用似然值检验对不同的树拓扑结构进行了评价。结果表明, 6种新测鲟类的线粒体基因组大小为16521—16766 bp, 编码13个蛋白质编码基因、22个转运RNA基因和2个核糖体基因, 与大多数已测的鲟类的线粒体基因组结构高度相似。基于23种鲟形目鱼类线粒体基因组数据, 系统发育分析的结果表明: (1)鲟形目的两个科, 匙吻鲟科(Polyodontidae)和鲟科(Acipenseridae)均为单系; (2)鲟科的内部亲缘关系复杂, 鲟属和鳇属的物种均不构成单系群。鲟科鱼类按分子系统发育重建结果可以分为3个类群: 尖吻鲟类(A. sturio - A. oxyrinchus clade)、大西洋鲟类(Atlantic clade)和太平洋鲟类(Pacific clade)。树拓扑结构的检验结果表明, 鲟科的系统发育关系为(尖吻鲟类(太平洋鲟类, 大西洋鲟类))。铲鲟属(Scaphirhynchus)是大西洋鲟类的基部类群。研究也说明线粒体基因组数据在鲟形目鱼类系统与进化研究方面具有重要应用价值。     

基于rDNA ITS序列对绒泡菌目黏菌系统发育的探讨

绒泡菌目Physarida是黏菌纲Myxogastria最大的一个目,对其系统发育关系的研究一直是根据形态特征。为了从分子水平探讨绒泡菌目乃至黏菌纲的系统发育关系,以黏菌r DNA ITS通用引物对绒泡菌目5属8种黏菌的r DNA ITS进行扩增和测序,结合Gen Bank中已有的黏菌r DNA ITS序列,利用贝叶斯推断法(Bayesian inference,BI)和最大似然法(Maximum likelihood,ML)构建系统发育树。结果表明:绒泡菌目不同物种的r DNA ITS区在碱基组成和长度上差异明显,长度为777–1 445bp,G+C mol%在53.4%–61.9%之间。绒泡菌目与发网菌目Stemonitida聚类为两个明显的分支,在绒泡菌目分支上,绒泡菌科Physaraceae和钙皮菌科Didymiaceae各聚为一支,支持了形态学上以孢丝是否具有石灰质为依据区分这两个科的观点。由多份不同地理来源的鳞钙皮菌Didymium squamulosum材料组成的钙皮菌科又形成3个分支,证实了这个形态种是由地域来源广泛、繁殖亲和性各异和遗传变异较大的不同生物种组成的复合体。     

Bayesian Methods for Examining Hardy–Weinberg Equilibrium

Summary .  Testing for Hardy–Weinberg equilibrium is ubiquitous and has traditionally been carried out via frequentist approaches. However, the discreteness of the sample space means that uniformity of  p -values under the null cannot be assumed, with enumeration of all possible counts, conditional on the minor allele count, offering a computationally expensive way of  p -value calibration. In addition, the interpretation of the subsequent  p -values, and choice of significance threshold depends critically on sample size, because equilibrium will always be rejected at conventional levels with large sample sizes. We argue for a Bayesian approach using both Bayes factors, and the examination of posterior distributions. We describe simple conjugate approaches, and methods based on importance sampling Monte Carlo. The former are convenient because they yield closed-form expressions for Bayes factors, which allow their application to a large number of single nucleotide polymorphisms (SNPs), in particular in genome-wide contexts. We also describe straightforward direct sampling methods for examining posterior distributions of parameters of interest. For large numbers of alleles at a locus we resort to Markov chain Monte Carlo. We discuss a number of possibilities for prior specification, and apply the suggested methods to a number of real datasets.     

Hypothesis testing for the genetic background of quantitative traits

The testing of Bayesian point null hypotheses on variance component models have resulted in a tough assignment for which no clear and generally accepted method exists. In this work we present what we believe is a succeeding approach to such a task. It is based on a simple reparameterization of the model in terms of the total variance and the proportion of the additive genetic variance with respect to it, as well as on the explicit inclusion on the prior probability of a discrete component at origin. The reparameterization was used to bypass an arbitrariness related to the impropriety of uninformative priors onto unbounded variables while the discrete component was necessary to overcome the zero probability assigned to sets of null measure by the usual continuous variable models. The method was tested against computer simulations with appealing results.     

Elicitation of a beta prior for Bayesian inference in clinical trials

When making Bayesian inferences we need to elicit an expert's opinion to set up the prior distribution. For applications in clinical trials, we study this problem with binary variables. A critical and often ignored issue in the process of eliciting priors in clinical trials is that medical investigators can seldom specify the prior quantities with precision. In this paper, we discuss several methods of eliciting beta priors from clinical information, and we use simulations to conduct sensitivity analyses of the effect of imprecise assessment of the prior information. These results provide useful guidance for choosing methods of eliciting the prior information in practice.     

利用序列保守模体和局部构象信息预测转录因子结合位点

转录因子结合位点的计算预测是研究基因转录调控的重要环节,但常用的位置特异得分矩阵方法预测特异性偏低.通过深入分析结合位点的生物特征,提出了一种综合利用序列保守模体和局部构象信息的结合位点预测方法,以极大相关得分矩阵作为保守模体的描述模型,并根据二苷参数模型计算位点序列的局部构象,将两类信息得分组合为多维特征向量,在二次判别分析的框架下进行训练和滑动预测.预测过程中还引入了位置信息量以优化似然得分和过滤备选结果.针对大肠杆菌CRP和Fis结合位点数据的留一法测试结果表明,描述模型的改进和多种信息的融合能有效地改善预测方法的性能,大幅度提高特异性.     

利用表达序列标签电子克隆cDNA全序列的策略

基因组计划的进展及表达序列标签数据的迅速扩增使得电子克隆方法孕育而生,为进行基因克隆开辟了一条新的路径。介绍了表达序列标签和电子克隆的原理及过程,重点分析电子克隆过程中遇到的问题及解决方法,展望其在新基因功能研究中的作用。     

Accounting for uncertainty in the tree topology has little effect on the decision-theoretic approach to model selection in phylogeny estimation

Currently available methods for model selection used in phylogenetic analysis are based on an initial fixed-tree topology. Once a model is picked based on this topology, a rigorous search of the tree space is run under that model to find the maximum-likelihood estimate of the tree (topology and branch lengths) and the maximum-likelihood estimates of the model parameters. In this paper, we propose two extensions to the decision-theoretic (DT) approach that relax the fixed-topology restriction. We also relax the fixed-topology restriction for the Bayesian information criterion (BIC) and the Akaike information criterion (AIC) methods. We compare the performance of the different methods (the relaxed, restricted, and the likelihood-ratio test [LRT]) using simulated data. This comparison is done by evaluating the relative complexity of the models resulting from each method and by comparing the performance of the chosen models in estimating the true tree. We also compare the methods relative to one another by measuring the closeness of the estimated trees corresponding to the different chosen models under these methods. We show that varying the topology does not have a major impact on model choice. We also show that the outcome of the two proposed extensions is identical and is comparable to that of the BIC, Extended-BIC, and DT. Hence, using the simpler methods in choosing a model for analyzing the data is more computationally feasible, with results comparable to the more computationally intensive methods. Another outcome of this study is that earlier conclusions about the DT approach are reinforced. That is, LRT, Extended-AIC, and AIC result in more complicated models that do not contribute to the performance of the phylogenetic inference, yet cause a significant increase in the time required for data analysis.     

Bayesian Insight into a Robust Test for Linear Contrast Based on Asymmetric Censored Samples

A robust test for linear contrast using modified maximum likelihood estimators based on symmetrically censored samples proposed by Tiku (1973, 1982a) is studied in this paper from the Bayesian point of view. The effects of asymmetric censoring on this testing procedure is investigated and a good approximation to its posterior distribution in this case is worked out. We also present an example which illustrates the method of obtaining the highest posterior density interval for the linear combination of the unknown location parameters.     

Detection of Seven Major Evolutionary Lineages in Cyanobacteria Based on the 16S rRNA Gene Sequence Analysis with New Sequences of Five Marine Synechococcus Strains

Although molecular phylogenetic studies of cyanobacteria on the basis of the 16S rRNA gene sequence have been reported, the topologies were unstable, especially in the inner branchings. Our analysis of 16S rRNA gene phylogeny by the maximum-likelihood and neighbor-joining methods combined with rate homogeneous and heterogeneous models revealed seven major evolutionary lineages of the cyanobacteria, including prochlorophycean organisms. These seven lineages are always stable on any combination of these methods and models, fundamentally corresponding to phylogenetic relationships based on other genes, e.g., psbA, rbcL, rnpB, rpoC, and tufA. Moreover, although known genotypic and phenotypic characters sometimes appear paralleled in independent lineages, many characters are not contradictory within each group. Therefore we propose seven evolutionary groups as a working hypothesis for successive taxonomic reconstruction. New 16S rRNA sequences of five unicellular cyanobacterial strains, PCC 7001, PCC 7003, PCC 73109, PCC 7117, and PCC 7335 of Synechococcus sp., were determined in this study. Although all these strains have been assigned to ``marine clusters B and C,' they were separated into three lineages. This suggests that the organisms classified in the genus Synechococcus evolved diversely and should be reclassified in several independent taxonomic units. Moreover, Synechococcus strains and filamentous cyanobacteria make a monophyletic group supported by a comparatively high statistical confidence value (80 to 100%) in each of the two independent lineages; therefore, these monophylies probably reflect the convergent evolution of a multicellular organization. Received: 3 September 1998 / Accepted: 30 November 1998