ToppCluster: a multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems

Abstract

ToppCluster is a web server application that leverages a powerful enrichment analysis and underlying data environment for comparative analyses of multiple gene lists. It generates heatmaps or connectivity networks that reveal functional features shared or specific to multiple gene lists. ToppCluster uses hypergeometric tests to obtain list-specific feature enrichment P-values for currently 17 categories of annotations of human-ortholog genes, and provides user-selectable cutoffs and multiple testing correction methods to control false discovery. Each nameable gene list represents a column input to a resulting matrix whose rows are overrepresented features, and individual cells per-list P-values and corresponding genes per feature. ToppCluster provides users with choices of tabular outputs, hierarchical clustering and heatmap generation, or the ability to interactively select features from the functional enrichment matrix to be transformed into XGMML or GEXF network format documents for use in Cytoscape or Gephi applications, respectively. Here, as example, we demonstrate the ability of ToppCluster to enable identification of list-specific phenotypic and regulatory element features (both cis-elements and 3′UTR microRNA binding sites) among tissue-specific gene lists. ToppCluster’s functionalities enable the identification of specialized biological functions and regulatory networks and systems biology-based dissection of biological states. ToppCluster can be accessed freely at http://toppcluster.cchmc.org.

Pediatric Crohn disease patients exhibit specific ileal transcriptome and microbiome signature

“…These analyses provided a way to identify which known transcriptional regulators, biologic processes, and immune cell types were likely to be upregulated or downregulated within the ileum based on a given gene expression pattern. Analyses were conducted using ToppGene (20), ToppCluster (21), and Ingenuity Pathway Analysis software. The relative degree of upregulation or downregulation of a given transcriptional regulator or biologic process was provided by the activation z score obtained as an output from Ingenuity Pathway Analysis software (Supplemental Figure 2B), while P values for the specific cell type, pathway, phenotype, and biologic function associated with upregulated or downregulated genes were obtained as an output from ToppGene (Supplemental Excel files 4-6).…”

“…Immunohistochemistry confirmed the expected apical localization of DUOX2 within villous enterocytes in the CD ileum, in conjunction with suppression of epithelial APOA1 and evidence of increased lipid peroxidation (Figure 2A). We next performed functional annotation enrichment analyses of the DUOX2 and APOA1 gene coexpression signatures using Ingenuity Pathway Analysis, ToppCluster (21), and Cytoscape (ref. 27 and Figure 2B).…”

RNAseq profiling of primary microglia and astrocyte cultures in near-term ovine fetus: A glial in vivo-in vitro multi-hit paradigm in large mammalian brain

“…To select relevant genes among up and down regulated DE genes, perform enrichment analysis with ToppGenes and ToppCluster (Chen et al, 2009;Kaimal et al, 2010) for functional annotation enrichment pathways, biologic process and pathway with FDR p < 0.05.…”

Metadichol, A Novel ROR Gamma Inverse Agonist and Its Applications in Psoriasis

“…with a safe product like Metadichol [36,37,38]. Based on the experimental finding of Metadichol binding to the receptors that have a role in Psoriasis a software program like Topp Cluster [39,40] show that these clusters of genes target many skin related disease as shown in Figure 21. All Diseases are connected through networks, and their complexity suggests that there is a need to modulate multiple targets for a superior therapeutic effect compared to ligands focused on a single target.…”