Abstract
BackgroundDysregulated gene expression patterns have been reported in several mental disorders. Limited by the difficulty of obtaining samples, psychiatric molecular mechanism research still relies heavily on clues from genetics studies. By using reference data from brain expression studies, multiple types of comprehensive gene expression pattern analysis have been performed on psychiatric genetic results. These systems-level spatial-temporal expression pattern analyses provided evidence on specific brain regions, developmental stages and molecular pathways that are possibly involved in psychiatric pathophysiology. At present, there is no online tool for such systematic analysis, which hinders the applications of analysis by non-informatics researchers such as experimental biologists and clinical molecular biologists.ResultsWe developed the BEST web server to support Brain Expression Spatio-Temporal pattern analysis. There are three highlighted features of BEST: 1) visualization: it generates user-friendly visual results that are easy to interpret, including heatmaps, Venn diagrams, gene co-expression networks and cluster-based Manhattan gene plots; these results illustrate the complex spatio-temporal expression patterns, including expression quantification and correlation between genes; 2) integration: it provides comprehensive human brain spatio-temporal expression patterns by integrating data from currently available databases; 3) multi-dimensionality: it analyses input genes as both a whole set and several subsets (clusters) which are enriched according to co-expression patterns, and it also presents the correlation between genetic and expression data.ConclusionsTo the best of our knowledge, BEST is the first data tool to support comprehensive human brain spatial-temporal expression pattern analysis. It helps to bridge disease-related genetic studies and mechanism studies, provides clues for key gene and molecular system identification, and supports the analysis of disease sensitive brain region and age stages. BEST is freely available at http://best.psych.ac.cn.
Highlights
Dysregulated gene expression patterns have been reported in several mental disorders
The expression statuses of interest genes were reviewed in different brain regions and age stages; the potential functional combinations of genes of interest were presented by their enrichment status in coexpression gene clusters, which were generated by Weighted Correlation Network Analysis (WGCNA) [17]
A job is often finished in several minutes, and the results page will be accessed automatically; a user can retrieve the result later by visiting the results URL link that is generated after job submission
Summary
For analysis with reference to RNA-Seq data from Brainspan (dataset 1) and microarray data from the Allen Brain Atlas (dataset 2), heatmaps in the Expression heatmap of enriched clusters Except for average expression quantification of all inputs, BEST calculates the average expression quantifications of genes in each enriched cluster and presents them in expression heatmap form. 262 genes were mapped from inputs and the detail gene list can be queried from the “Gene_set.txt” in the downloadable results fold These genes were enriched respectively in five, one and four co-expression clusters from the three selected data resources in the context of 16 by 10 spatio-temporal matrix. Specific for dataset 1, these genes were enriched in eight clusters in the context of 25 by 9 matrix These enriched coexpression clusters presented complex spatio-temporal expression features. It may play important role in the cluster-related biological processes
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