MonaGO: a novel gene ontology enrichment analysis visualisation system

Abstract

Background: Gene ontology (GO) enrichment analysis is frequently undertaken during exploration of various -omics data sets. Despite the wide array of tools available to biologists to perform this analysis, meaningful visualisation of the overrepresented GO in a manner which is easy to interpret is still lacking.

Results: Monash Gene Ontology (MonaGO) is a novel web-based visualisation system that provides an intuitive, interactive and responsive interface for performing GO enrichment analysis and visualising the results. MonaGO supports gene lists as well as GO terms as inputs. Visualisation results can be exported as high-resolution images or restored in new sessions, allowing reproducibility of the analysis. An extensive comparison between MonaGO and 11 state-of-the-art GO enrichment visualisation tools based on 9 features revealed that MonaGO is a unique platform that simultaneously allows interactive visualisation within one single output page, directly accessible through a web browser with customisable display options.

Conclusion: MonaGO combines dynamic clustering and interactive visualisation as well as customisation options to assist biologists in obtaining meaningful representation of overrepresented GO terms, producing simplified outputs in an unbiased manner. MonaGO will facilitate the interpretation of GO analysis and will assist the biologists into the representation of the results.

Keywords: GO enrichment; Gene ontology; Interactive visualisation; Semantic web; Web services.

Fig. 1

MonaGO’s hierarchical clustering algorithm (Algorithm 1) to produce the dynamic chord diagram

Fig. 2

The main visualisation interface of MonaGO consisting of three components: A (left) the main visualisation panel on the left that shows the chord diagram of GO terms that can be hierarchically and dynamically clustered, B (top right) search box, and C (bottom right) the details panel with dynamic GO hierarchy visualisation

Fig. 3

An example usage of the manual clustering feature of MonaGO which allows to dynamically collapse or expand nodes in the hierarchy of enriched terms: A the GO chord diagram before clustering where GO1 and GO2 are to be merged and, B the GO chord diagram after clustering

Fig. 4

Using MonaGO to study functions of genes involved reprogramming fibroblasts to a pluripotent state. A List of clustered terms from GO enrichment of these genes using DAVID: A.i term clustering table; A.ii common genes display. B MonaGO clustering result of the same gene sets used in A, showing B.i clustering of the full set of terms; and B.ii manual clustering by node collapsing from fibroblast gene cluster 4 in Nefzget et al. 2017. C Visualisation of genes from 6 representative fibroblasts clusters by C.i REVIGO and C.ii MonaGO

Fig. 5

A Section of MonaGO’s visualisation with set of cardiac genes from zebrafish and overlapping genes as distance measurement. The GO terms ‘central nervous projection neuron axonogenesis’ and ‘anterior/posterior axon guidance’ showing 100% of overlapping genes, are highlighted in yellow. B Same visualisation as A but using Resnik similarity as distance measurement instead

Fig. 6

GO hierarchy between the Biological Process terms ‘central nervous system project neuron axonegenesis and ‘anterior/posterior axon guidance.’ These have Resnik similarity of 3.638, with their Most Informative Ancestor being ‘axonogenesis.’

Fig. 7

Section of MonaGO visualisation with set of cardiac genes from zebrafish and Resnik similarity as distance measurement. The GO terms ‘liver development’, ‘determination of liver left/right asymmetry’ and ‘thyroid gland development’ form a cluster of semantically similar terms with no genes overlap. This cluster shares overlapping genes with ‘determination of heart left/right asymmetry’ (highlighted in yellow)

Fig. 8

GO hierarchy between the Biological Process terms ‘determination of heart left/right asymmetry’ and ‘determination of liver left/right asymmetry.’ These have Resnik similarity of 4.229, with their Most Informative Ancestor being ‘determination of left/right symmetry.’