Evaluating the differential expression of a set of genes belonging to a common biological process or ontology has proven to be a very useful tool for biological discovery. However, existing gene-set association methods are limited to applications that evaluate differential expression across k ≥ 2 treatment groups or biological categories. This limitation precludes researchers from most effectively evaluating the association with other phenotypes that may be more clinically meaningful, such as quantitative variables or censored survival time variables. Projection onto the Orthogonal Space Testing (POST) is proposed as a general procedure that can robustly evaluate the association of a gene-set with several different types of phenotypic data (categorical, ordinal, continuous, or censored). For each gene-set, POST transforms the gene profiles into a set of eigenvectors and then uses statistical modeling to compute a set of z-statistics that measure the association of each eigenvector with the phenotype. The overall gene-set statistic is the sum of squared z-statistics weighted by the corresponding eigenvalues. Finally, bootstrapping is used to compute a p-value. POST may evaluate associations with or without adjustment for covariates. In simulation studies, it is shown that the performance of POST in evaluating the association with a categorical phenotype is similar to or exceeds that of existing methods. In evaluating the association of 875 biological processes with the time to relapse of pediatric acute myeloid leukemia, POST identified the well-known oncogenic WNT signaling pathway as its top hit. These results indicate that POST can be a very useful tool for evaluating the association of a gene-set with a variety of different phenotypes.

MOTIVATION: There is a substantial body of works in the biology literature that seeks to characterize the cyclic behavior of genes during cell division. Gene expression microarrays made it possible to measure the expression profiles of thousands of genes simultaneously in time-course experiments to assess changes in the expression levels of genes over time. In this context, the commonly used procedures for testing include the permutation test by de Lichtenberg et al. and the Fisher's G-test, both of which are designed to evaluate periodicity against noise. However, it is possible that a gene of interest may have expression that is neither cyclic nor just noise. Thus, there is a need for a new test for periodicity that can identify cyclic patterns against not only noise but also other non-cyclic patterns such as linear, quadratic or higher order polynomial patterns. RESULTS: To address this weakness, we have introduced an empirical Bayes approach to test for periodicity and compare its performance in terms of sensitivity and specificity with that of the permutation test and Fisher's G-test through extensive simulations and by application to a set of time-course experiments on the Schizosaccharomyces pombe cell-cycle gene expression. We use 'conserved' and 'cycling' genes by Lu et al. to assess the sensitivity and CESR genes by Chenet al. to assess the specificity of our new empirical Bayes method. AVAILABILITY AND IMPLEMENTATION: The SAS Macro for our empirical Bayes test for periodicity is included in the supplementary materials along with a sample run of the MACRO program. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

In this work, we characterize genes using an oligonucleotide affymetrix gene expression dataset and propose a novel gene selection method based on samples from the posterior distributions of class-specific gene expression measures. We construct a hierarchical Bayesian framework for a random effect ANOVA model that allows us to obtain the posterior distributions of the class-specific gene expressions. We also formalize a novel class prediction scheme based on the samples from new posterior distributions of group specific gene expressions. Our experimental results show the class-discriminating power of the selected genes. Furthermore, we demonstrate that our prediction scheme classifies tissue samples into appropriate treatment groups with high accuracy. The computations are implemented by using Gibbs sampling. We compare the efficacy of our proposed gene selection and prediction methods with that of Pomeroy et. al (Nature, 2002) on the same CNS tumor sample dataset.

This paper proposes a procedure for finding significance of gene ranking. The microarray data usually has a large number of genes that are not differentially expressed across multiple conditions. In microarray analysis, it is a common practice to first discard these genes as uninformative based on some filtering criterion. This filtering process results in the information loss as the uninformative genes may be used to construct an empirical distribution of genes under the null hypothesis. The distribution of the non-differentially expressed genes is complex and may be regarded as a mixture of distributions. The null hypothesis is that the gene is not differentially expressed. The significance of the differentially expressed genes therefore may be estimated by using the empirical distribution function of the large number of insignificant genes. The proposed method is efficient, less computation intensive and may be applied on microarray datasets of any sample size.