Graph-based exploitation of gene ontology using GOxploreR for scrutinizing biological significance

Abstract

Gene ontology (GO) is an eminent knowledge base frequently used for providing biological interpretations for the analysis of genes or gene sets from biological, medical and clinical problems. Unfortunately, the interpretation of such results is challenging due to the large number of GO terms, their hierarchical and connected organization as directed acyclic graphs (DAGs) and the lack of tools allowing to exploit this structural information explicitly. For this reason, we developed the R package GOxploreR. The main features of GOxploreR are (I) easy and direct access to structural features of GO, (II) structure-based ranking of GO-terms, (III) mapping to reduced GO-DAGs including visualization capabilities and (IV) prioritizing of GO-terms. The underlying idea of GOxploreR is to exploit a graph-theoretical perspective of GO as manifested by its DAG-structure and the containing hierarchy levels for cumulating semantic information. That means all these features enhance the utilization of structural information of GO and complement existing analysis tools. Overall, GOxploreR provides exploratory as well as confirmatory tools for complementing any kind of analysis resulting in a list of GO-terms, e.g., from differentially expressed genes or gene sets, GWAS or biomarkers. Our R package GOxploreR is freely available from CRAN.