ToppGene Suite for gene list enrichment analysis and candidate gene prioritization

Abstract

ToppGene Suite (http://toppgene.cchmc.org; this web site is free and open to all users and does not require a login to access) is a one-stop portal for (i) gene list functional enrichment, (ii) candidate gene prioritization using either functional annotations or network analysis and (iii) identification and prioritization of novel disease candidate genes in the interactome. Functional annotation-based disease candidate gene prioritization uses a fuzzy-based similarity measure to compute the similarity between any two genes based on semantic annotations. The similarity scores from individual features are combined into an overall score using statistical meta-analysis. A P-value of each annotation of a test gene is derived by random sampling of the whole genome. The protein–protein interaction network (PPIN)-based disease candidate gene prioritization uses social and Web networks analysis algorithms (extended versions of the PageRank and HITS algorithms, and the K-Step Markov method). We demonstrate the utility of ToppGene Suite using 20 recently reported GWAS-based gene–disease associations (including novel disease genes) representing five diseases. ToppGene ranked 19 of 20 (95%) candidate genes within the top 20%, while ToppNet ranked 12 of 16 (75%) candidate genes among the top 20%.

Proteome profiling of extracellular vesicles captured with the affinity peptide Vn96: comparison of Laemmli and TRIzol© protein‐extraction methods

“…Proteomics data were assessed to identify enriched gene ontologies using the ToppFun application within the ToppGene suite [16]. Where proteomic-based gene annotation did not match HUGO gene symbols, ToppFun performed automatic re-annotation.…”

Disease gene identification strategies for exome sequencing

“…44 Recently, Erlich et al 45 demonstrated how gene prediction tools typically applied in combination with traditional mapping approaches, can also successfully be applied to prioritize candidate genes from exome resequencing experiments. They used three different bioinformatics tools (SUSPECTS, 46 ToppGene, 47 and Endeavour 15 ) to prioritize KIF1A as the most likely candidate gene for hereditary spastic paraparesis. Prioritization of the variants itself using MutationTaster, 48 Polyphen, 49 and SIFT 50 independently pointed to the variant in KIF1A as being the most likely pathogenic variant.…”

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.…”