Using the ratio of means as the effect size measure in combining results of microarray experiments

<p>Abstract</p> <p>Background</p> <p>Development of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small.</p> <p>Results</p> <p>We propose a re-parameterization of the traditional mean difference based effect measure by using the log ratio of means as an effect size measure for each gene in each study. The estimated effect sizes for all studies were then combined under two modeling frameworks: the quality-unweighted random effects models and the quality-weighted random effects models. We defined the quality measure as a function of the detection p-value, which indicates whether a transcript is reliably detected or not on the Affymetrix gene chip. The new effect size measure is evaluated and compared under the quality-weighted and quality-unweighted data integration frameworks using simulated data sets, and also in several data sets of prostate cancer patients and controls. We focus on identifying differentially expressed biomarkers for prediction of cancer outcomes.</p> <p>Conclusion</p> <p>Our results show that the proposed effect size measure (log ratio of means) has better power to identify differentially expressed genes, and that the detected genes have better performance in predicting cancer outcomes than the commonly used effect size measure, the standardized mean difference (SMD), under both quality-weighted and quality-unweighted data integration frameworks. The new effect size measure and the quality-weighted microarray data integration framework provide efficient ways to combine microarray results.</p

Tissue-specific transcriptional biomarkers in medicinal plants: Application of large-scale meta-analysis and computational systems biology

© 2019 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (January 2019) in accordance with the publisher’s archiving policyBiosynthesis of secondary metabolites in plant is a complex process, regulated by many genes and influenced by several factors. In recent years, the next-generation sequencing (NGS) technology and advanced statistical analysis such as meta-analysis and computational systems biology have provided novel opportunities to overcome biological complexity. Here, we performed a meta-analysis on publicly available transcriptome datasets of twelve economically significant medicinal plants to identify differentially expressed genes (DEGs) between shoot and root tissues and to find the key molecular features which may be effective in the biosynthesis of secondary metabolites. Meta-analysis identified a total of 880 genes with differential expression between two tissues. Functional enrichment and KEGG pathway analysis indicated that the functions of those DEGs are highly associated with the developmental process, starch metabolic process, response to stimulus, porphyrin and chlorophyll metabolism, biosynthesis of secondary metabolites and phenylalanine metabolism. In addition, systems biology analysis of the DEGs was applied to find protein–protein interaction network and discovery of significant modules. The detected modules were associated with hormone signal transduction, transcription repressor activity, response to light stimulus and epigenetic processes. Finally, analysis was extended to search for putative miRNAs that are associated with DEGs. A total of 31 miRNAs were detected which belonged to 16 conserved families. The present study provides a comprehensive view to better understand the tissue-specific expression of genes and mechanisms involved in secondary metabolites synthesis and may provide candidate genes for future researches to improve yield of secondary metabolites

A COMPARISON OF META-ANALYSIS METHODS FOR DETECTING DIFFERENTIALLY EXPRESSED GENES IN MICROARRAY EXPERIMENTS: AN APPLICATION TO MALIGNANT PLEURAL MESOTHELIOMA DATA

The proliferation of microarray experiments and the increasing availability of relevant amount of data in public repositories have created a need for meta-analysis methods to efficiently integrate and validate microarray results from independent but related studies. Despite its increasing popularity, meta-analysis of microarray data is not without problems. In fact, although it shares many features with traditional meta-analysis, most classical meta-analysis methods cannot be directly applied to microarray experiments because of their unique issues. Several meta-analysis techniques have been proposed in the context of microarrays. However, only recently a comprehensive framework to carry out microarray data meta-analysis has been proposed. Moreover very few software packages for microarray meta-analysis implementation exist and most of them either have unclear manuals or are not easy to apply. We applied four meta-analysis methods, the Stouffer’s method, the moderated effect size combination approach, the t-based hierarchical modeling and the rank product method, to a set of three microarray studies on malignant pleural mesothelioma. We focused on differential expression analysis between normal and malignant mesothelioma pleural tissues. Both unfiltered and filtered data were analyzed. The lists of differentially expressed genes provided by each method for either kind of data were compared, also by pathway analysis. These comparisons highlighted a poor overlap between the lists of differentially expressed genes and the related pathways obtained using the unfiltered data. Conversely, a higher concordance of the results, both at the gene and the pathway level, was observed when filtered data were considered. The fact that a significant number of genes were identified by only one of the tested methods shows that the gene ranking is based on different perspectives. In fact, the analyzed methods are based on different assumptions and focus on diverse aspects in selecting significant genes. Since so far there is no consensus on what is (are) the ‘best’ meta-analysis method(s), it may be useful to select candidate genes for further analysis using a combination of different meta-analysis methods. In particular, differentially expressed genes detected by more than one method may be considered as the most reliable ones while genes identified by only a single method may be further explored to expand the knowledge of the biological phenomenon of interest