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. 2019 Apr 3;10(1):1523.
doi: 10.1038/s41467-019-09234-6.

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

Yingyao Zhou  1 , Bin Zhou  2 , Lars Pache  3 , Max Chang  4 , Alireza Hadj Khodabakhshi  2 , Olga Tanaseichuk  2 , Christopher Benner  4 , Sumit K Chanda  5
Affiliations

Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

Yingyao Zhou et al. Nat Commun. .

Abstract

A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Schematic outline of the Metascape analysis workflow. Upon gene list submission, Custom Analysis enables users to navigate the analysis workflow and output a report. The Express Analysis instead takes a streamlined approach by running the analysis steps with popular default settings, simplifying the user experience
Fig. 2
Fig. 2
Visualizations of functional enrichment and interactome analysis results. a Screenshot of a portion of the directed acyclic graph rendered by Babelomics based on enriched GO terms. b Screenshot of a portion of the gene-term association matrix rendered by g:profile, where enriched GO terms are organized hierarchically. c Screenshot of a portion of the tabular display of enriched terms rendered by DAVID based on all GO terms, KEGG pathways, Reactome, and CORUM. The terms related to “viral gene expression” were missed in the visualizations generated by Babelomics and g:profile, but were identified by DAVID (in cluster 8 with ranks around 20). d Metascape bar graph for viewing top non-redundant enrichment clusters, one per cluster, using a discrete color scale to represent statistical significance. e Metascape enrichment network visualization showing the intra-cluster and inter-cluster similarities of enriched terms, up to ten terms per cluster. Cluster annotations are shown in color code. f A complex interactome network generated by g:profile with the Brass gene list. g Metascape visualization of the interactome network formed by all 121 gene candidates from the Brass list, where the MCODE complexes are colored according to their identities. h Seven MCODE complexes automatically identified in Metascape, colored by their identities. Their functional labels are generated based on the top-three functional enriched terms, if available
Fig. 3
Fig. 3
Visualizations of meta-analysis results based on multiple gene lists. a Heatmap showing the top enrichment clusters, one row per cluster, using a discrete color scale to represent statistical significance. Gray color indicates a lack of significance. The category GO:0016032 (viral process) is common to all studies, while GO:0046777 (protein autophosphorylation) is enriched exclusively in a single study, and is therefore likely a process associated with one particular experimental system. b Enrichment network visualization for results from the three gene lists, where nodes are represented by pie charts indicating their associations with each input study. Cluster labels were added manually. Color code represents the identities of gene lists. The network shows that processes such as viral gene expression, nucleocytoplasmic transport, and cellular response to external stimuli are generally shared among all three lists. RNA metabolism is shared between the Brass and Karlas lists; cellular development processes are mostly shared between the Karlas and Konig lists. c Selected MCODE components identified from the combined list of 541 genes, where each node represents a protein with a pie chart encoding its origin. The complex related to viral process is shared among all three lists, while the complex related to the MAP kinase cascade is specific to the Konig list. Supplementary Figure 12 presents all MCODE components identified
Fig. 4
Fig. 4
Schematic diagram of the semi-automatic data synchronization workflow
Fig. 5
Fig. 5
Citation statistics illustrating the use of Metascape visualizations in publications. a 62% of publications adopted visualizations prepared by Metascape. b Visualization types sorted according to their popularity, where the enrichment bar graph, network, and heatmap are frequently used to summarize functional enrichment outputs
See this image and copyright information in PMC

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