A Bayesian mixture model for differential gene expression

Summary.  We propose model-based inference for differential gene expression, using a nonparametric Bayesian probability model for the distribution of gene intensities under various conditions. The probability model is a mixture of normal distributions. The resulting inference is similar to a popular empirical Bayes approach that is used for the same inference problem. The use of fully model-based inference mitigates some of the necessary limitations of the empirical Bayes method. We argue that inference is no more difficult than posterior simulation in traditional nonparametric mixture-of-normal models. The approach proposed is motivated by a microarray experiment that was carried out to identify genes that are differentially expressed between normal tissue and colon cancer tissue samples. Additionally, we carried out a small simulation study to verify the methods proposed. In the motivating case-studies we show how the nonparametric Bayes approach facilitates the evaluation of posterior expected false discovery rates. We also show how inference can proceed even in the absence of a null sample of known non-differentially expressed scores. This highlights the difference from alternative empirical Bayes approaches that are based on plug-in estimates.     

Efficient Stratified Testing Procedure for a False Discovery Rate

The false discovery rate (FDR) has become a popular error measure in the large-scale simultaneous testing. When data are collected from heterogenous sources and form grouped hypotheses testing, it may be beneficial to use the distinct feature of groups to conduct the multiple hypotheses testing. We propose a stratified testing procedure that uses different FDR levels according to the stratification features based on p-values. Our proposed method is easy to implement in practice. Simulations studies show that the proposed method produces more efficient testing results. The stratified testing procedure minimizes the overall false negative rate (FNR) level, while controlling the overall FDR. An example from a type II diabetes mice study further illustrates the practical advantages of this new approach.     

文明基因的解读——水流动力学的启示

通过比较河流动力学与海洋动力学的不同,揭示水流动力学机制对世界文明的深远影响。海洋动力学机制使西方文明彰显出开放、多元的梯形结构,河流动力学机制则构造了大河文明的基因。     

A new class of mixture models for differential gene expression in DNA microarray data

One of the fundamental issues in analyzing microarray data is to determine which genes are expressed and which ones are not for a given group of subjects. In datasets where many genes are expressed and many are not expressed (i.e., underexpressed), a bimodal distribution for the gene expression levels often results, where one mode of the distribution represents the expressed genes and the other mode represents the underexpressed genes. To model this bimodality, we propose a new class of mixture models that utilize a random threshold value for accommodating bimodality in the gene expression distribution. Theoretical properties of the proposed model are carefully examined. We use this new model to examine the problem of differential gene expression between two groups of subjects, develop prior distributions, and derive a new criterion for determining which genes are differentially expressed between the two groups. Prior elicitation is carried out using empirical Bayes methodology in order to estimate the threshold value as well as elicit the hyperparameters for the two component mixture model. The new gene selection criterion is demonstrated via several simulations to have excellent false positive rate and false negative rate properties. A gastric cancer dataset is used to motivate and illustrate the proposed methodology.     

Locating genes involved in human diseases

The increasing amount of information that is becoming available about the structure and composition of the DNA constituting the human chromosomes has provided new opportunities to locate genes that affect susceptibilities to a range of diseases. The accurate location of these genes is important in genetic counselling and in understanding the effects of genes that may result in disease. Various methods of analysing the data when DNA information is available at a single marker locus for an affected child and his or her parents are reviewed and applied to data on insulin-dependent diabetes mellitus . The importance of distinguishing between the association of alleles at a marker locus and at a disease locus resulting from chromosomal linkage from that resulting from other causes is emphasized.     

植物抗寒基因研究进展

本文综述了国内外抗寒基因的研究方法和抗寒基因的表达控制的新进展。     

The genetic heterogeneity of deer mouse populations ( Peromyscus maniculatus ) in an insular landscape

A survey of the genetic variability in deer mouse populations was performed using specimens collected from six different islands on a lake covering approximately 50 km². Random amplified polymorphic DNA (RAPD) was used to measure the extent of the genetic differences in this insular system. An analysis of molecular variance (AMOVA) revealed that populations are clearly separated at this microgeographic scale (F _st = 0.13863; P < 0.001). The homogeneity of molecular variance test (HOMOVA) indicated that within-population levels vary greatly (B _p = 0.76831; P < 0.001). The within-population molecular variance was found to be mainly correlated with the accessibility of the islands, computed as the inverse of the geographic distance separating an island from the lakeshore (r = 0.916; P < 0.003). Received: March 5, 1999 / Accepted: July 16, 1999     

采用非线性核支持向量机并基于基因表达数据的基因选择和分类

在基于微阵列的癌症分类中,由于变量(基因表达)较多,而实验条件较少,因此特征选择和分类方法非常重要。对于疾病诊断,分类器的性能直接影响到最终结果的准确性。本文提出一种新的基因选择和分类方法,这种方法使用基于递归特征排除(RFE)的非线性核支持向量机(SVM)。实验表明本文方法比其它线性分类方法具有更好的整体表现,如线性核支持向量机和Fisher线性判别分析方法;同样本文方法也比一些非线性分类方法更好,如采用非线性核的最小二乘支持向量机(LS-SVM)。实验除了使用测试集,还使用留一校验算法(leave-one-out)用于测试分类器的泛化性能。实验采用可通过互联网获得的AML/ALL数据集和遗传性乳腺癌数据集。     

Analysis of Survival Data with Group Lasso

Identification of influential genes and clinical covariates on the survival of patients is crucial because it can lead us to better understanding of underlying mechanism of diseases and better prediction models. Most of variable selection methods in penalized Cox models cannot deal properly with categorical variables such as gender and family history. The group lasso penalty can combine clinical and genomic covariates effectively. In this article, we introduce an optimization algorithm for Cox regression with group lasso penalty. We compare our method with other methods on simulated and real microarray data sets.