GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists

Abstract

BackgroundSince the inception of the GO annotation project, a variety of tools have been developed that support exploring and searching the GO database. In particular, a variety of tools that perform GO enrichment analysis are currently available. Most of these tools require as input a target set of genes and a background set and seek enrichment in the target set compared to the background set. A few tools also exist that support analyzing ranked lists. The latter typically rely on simulations or on union-bound correction for assigning statistical significance to the results.ResultsGOrilla is a web-based application that identifies enriched GO terms in ranked lists of genes, without requiring the user to provide explicit target and background sets. This is particularly useful in many typical cases where genomic data may be naturally represented as a ranked list of genes (e.g. by level of expression or of differential expression). GOrilla employs a flexible threshold statistical approach to discover GO terms that are significantly enriched at the top of a ranked gene list. Building on a complete theoretical characterization of the underlying distribution, called mHG, GOrilla computes an exact p-value for the observed enrichment, taking threshold multiple testing into account without the need for simulations. This enables rigorous statistical analysis of thousand of genes and thousands of GO terms in order of seconds. The output of the enrichment analysis is visualized as a hierarchical structure, providing a clear view of the relations between enriched GO terms.ConclusionGOrilla is an efficient GO analysis tool with unique features that make a useful addition to the existing repertoire of GO enrichment tools. GOrilla's unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation. GOrilla is publicly available at:

Landscape of nuclear transport receptor cargo specificity

“…Gene Ontology enrichment analysis was performed on ranked list of proteins using log‐transformed P ‐values or specificity scores using GOrilla (Eden et al , 2009) followed by GO term redundancy reduction performed by REVIGO (Supek et al , 2011). …”

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

“…Perform GO analysis with Gorilla; select significant networks (P < 0.03) for further analysis (Bauer et al, 2008;Eden et al, 2009). Functional classification of selected genes can be viewed in pie chart with Panther (Mi et al, 2016).…”

An integrative analysis of reprogramming in human isogenic system identified a clone selection criterion

“…Expression changes more than 2-fold and b-value differences more than 0.2 were considered significant. The gene ontology term analysis was performed using GREAT, 40 Gorilla, 41 and WebGestalt 42 tools. 3D principal component analyses (ellipsoids) of the expression data were constructed on the basis of the covariance matrix with 2 standard deviation scaling.…”