Dan Lin

FABIA: factor analysis for bicluster acquisition

Motivation: Biclustering of transcriptomic data groups genes and samples simultaneously. It is emerging as a standard tool for extracting knowledge from gene expression measurements. We propose a novel generative approach for biclustering called ‘FABIA: Factor Analysis for Bicluster Acquisition’. FABIA is based on a multiplicative model, which accounts for linear dependencies between gene expression and conditions, and also captures heavy-tailed distributions as observed in real-world transcriptomic data. The generative framework allows to utilize well-founded model selection methods and to apply Bayesian techniques. Results: On 100 simulated datasets with known true, artificially implanted biclusters, FABIA clearly outperformed all 11 competitors. On these datasets, FABIA was able to separate spurious biclusters from true biclusters by ranking biclusters according to their information content. FABIA was tested on three microarray datasets with known subclusters, where it was two times the best and once the second best method among the compared biclustering approaches. Availability: FABIA is available as an R package on Bioconductor (http://www.bioconductor.org). All datasets, results and software are available at http://www.bioinf.jku.at/software/fabia/fabia.html Contact: hochreit@bioinf.jku.at Supplementary information: Supplementary data are available at Bioinformatics online.

An Investigation on Performance of Significance Analysis of Microarray (SAM) for the Comparisons of Several Treatments with one Control in the Presence of Small-variance Genes

One of multiple testing problems in drug finding experiments is the comparison of several treatments with one control. In this paper we discuss a particular situation of such an experiment, i.e., a microarray setting, where the many-to-one comparisons need to be addressed for thousands of genes simultaneously. For a gene-specific analysis, Dunnetts single step procedure is considered within gene tests, while the FDR controlling procedures such as Significance Analysis of Microarrays (SAM) and Benjamini and Hochberg (BH) False Discovery Rate (FDR) adjustment are applied to control the error rate across genes. The method is applied to a microarray experiment with four treatment groups (three microarrays in each group) and 16,998 genes. Simulation studies are conducted to investigate the performance of the SAM method and the BH-FDR procedure with regard to controlling the FDR, and to investigate the effect of small-variance genes on the FDR in the SAM procedure.

Performance of Gene Selection and Classification Methods in a Microarray Setting: A Simulation Study

In a previous article, we investigated the performance of several classification methods for cDNA-microarrays. Via simulations, various experimental settings could be explored without having to conduct expensive microarray studies. For the selection of genes, on which classification was based, one particular method was applied. Gene selection is, however, a very important aspect of classification. We extend the previous study by considering several gene selection methods. Furthermore, the stability of the methods with respect to distributional assumptions is examined by also considering data simulated from a symmetric and asymmetric Laplace distribution, in addition to normally distributed microarray data.

Translation of disease associated gene signatures across tissues

It has recently been shown that disease associated gene signatures can be identified by profiling tissue other than the disease related tissue. In this paper, we investigate gene signatures for Irritable Bowel Syndrome (IBS) using gene expression profiling of both disease related tissue (colon) and surrogate tissue (rectum). Gene specific joint ANOVA models were used to investigate differentially expressed genes between the IBS patients and the healthy controls taken into account both intra and inter tissue dependencies among expression levels of the same gene. Classification algorithms in combination with feature selection methods were used to investigate the predictive power of gene expression levels from the surrogate and the target tissues. We conclude based on the analyses that expression profiles of the colon and the rectum tissue could result in better predictive accuracy if the disease associated genes are known.

A Comparison of Procedures for Controlling the False Discovery Rate in the Presence of Small Variance Genes: A Simulation Study

The Significance Analysis of Microarrays (SAM; Tusher et al., 2001) method is widely used in analyzing gene expression data while controlling the FDR by using resampling-based procedure in the microarray setting. One of the main components of the SAM procedure is the adjustment of the test statistic. The introduction of the fudge factor to the test statistic aims at deflating the large value of test statistics due to the small standard error of gene-expression. Lin et al. (2008) pointed out that the fudge factor does not effectively improve the power and the control of the FDR as compared to the SAM procedure without the fudge factor in the presence of small variance genes. Motivated by the simulation results presented in Lin et al. (2008), in this article, we extend our study to compare several methods for choosing the fudge factor in the modified t-type test statistics and use simulation studies to investigate the power and the control of the FDR of the considered methods.