ConceptGen: a gene set enrichment and gene set relation mapping tool

Abstract

Motivation: The elucidation of biological concepts enriched with differentially expressed genes has become an integral part of the analysis and interpretation of genomic data. Of additional importance is the ability to explore networks of relationships among previously defined biological concepts from diverse information sources, and to explore results visually from multiple perspectives. Accomplishing these tasks requires a unified framework for agglomeration of data from various genomic resources, novel visualizations, and user functionality.

Results: We have developed ConceptGen, a web-based gene set enrichment and gene set relation mapping tool that is streamlined and simple to use. ConceptGen offers over 20,000 concepts comprising 14 different types of biological knowledge, including data not currently available in any other gene set enrichment or gene set relation mapping tool. We demonstrate the functionalities of ConceptGen using gene expression data modeling TGF-beta-induced epithelial-mesenchymal transition and metabolomics data comparing metastatic versus localized prostate cancers.

Fig. 1.

Inter-connectivity among concept types. Connectivity is defined as s/n where s = No. of tests between concept types with q-value <0.05 and n = total number of possible connections. Values were clustered using complete linkage hierarchical clustering in R.

Fig. 2.

ConceptGen Network Graph after 30 min TGFβ-induction of A549 cells shows TGF-β receptors, SMAD proteins, Myod1 interactions, and transcription factor activity to be enriched. Shown are all concepts with q-value <0.05 after filtering for Gene Expression.

Fig. 3.

Heatmap of enriched Concept profiles throughout TGF-β-induced EMT transition in the A549 cell line for concept types other than GO and Gene Expression: rows are concepts from KEGG, Biocarta, and Panther Pathways, MiMI protein interactions, MeSH, Pfam and Transfac. All concepts with q-value <0.05 for ≥1 time point were clustered using −log₁₀(p-values) to create a ‘bird's eye view’ of which processes were turning on and off throughout the time course. For presentation, enriched concepts were summarized for each main cluster. Heatmaps for GO and gene expression concepts are presented in Supplementary Material.

Fig. 4.

ConceptGen Network Graph after 8hrs of TGFβ induction in A549 cells shows extracellular matrix, cell adhesion, cell movement and metallothioneins are enriched, consistent with the migratory and invasive phenotypes acquired during EMT. Shown are the top significant concepts from Pfam, MeSH, and MiMI. GO biological processes indicated that vascular and blood vessel development were also enriched.

Fig. 5.

Protein interactions among differentially expressed genes after 1hr of TGFβ induction in A549 cells, visualized by clicking on the gear icon for the uploaded concept in the network browser view, which links to the MiMI NetBrowser view of known protein interactions.