In sigven/oncoEnrichR: Cancer-dedicated gene set interpretation

Protein-protein interaction network

We here create dedicated protein-protein interaction networks for members of the query set, shown using data from the two largest resources on protein-protein interactions:
BioGRID - a biomedical interaction repository with data compiled through comprehensive curation efforts
STRING - database of known and predicted protein-protein interactions, including direct (physical) and indirect (functional) associations
Three different views are shown for each resource:
- Complete protein-protein interaction network, also showing proteins with no known interactions
- Network community structures, as detected by the fast greedy modularity optimization algorithm by Clauset et al.
- Network centrality/hub scores pr. node, as measured by Kleinberg's score
All detailed evidence for each interaction (STRING scores and BioGRID evidence items) are provided in the Excel output of oncoEnrichR

General network legend:
Target set proteins are shaped as circles, other interacting proteins are shaped as rectangles (note that sizes of nodes do not carry any value), drugs are shaped as diamonds
Target genes with strong/very strong support in Network of Cancer Genes/Cancer Gene Census/CancerMine of having tumor suppressive function are HIGHLIGHTED IN RED
Target genes with strong/very strong support in Network of Cancer Genes/Cancer Gene Census/CancerMine of having oncogenic function HIGHLIGHTED IN GREEN
Genes with evidence of having dual roles (both oncogenic and tumor suppressive) are HIGHLIGHTED IN BLACK
Targeted cancer drugs (from Open Targets Platform):
- Compounds in late (3-4) clinical development phases are HIGHLIGHTED IN ORANGE
- Compounds in early (1-2) clinical development phases are HIGHLIGHTED IN PURPLE
Use the mouse to zoom in/out, alter the position of nodes, mouse-over edges and nodes to view gene names/drug mechanism of actions (with indications)/interaction scores (evidence support)

PPI network - STRING {.tabset}

STRING interaction network type: r onc_enrich_report[['config']][['ppi']][['string']][['network_type']]
- This reflects the network_type parameter in the STRING API
The STRING network is expanded with n = r onc_enrich_report[['config']][['ppi']][['string']][['add_nodes']] proteins that interact with proteins in the query set
- This reflects the add_nodes parameter in the STRING API
Minimum STRING interaction confidence score required: r onc_enrich_report[['config']][['ppi']][['string']][['minimum_score']] (range 0-1)
- This reflects the required_score parameter in the STRING API
Drugs added to the STRING network: r onc_enrich_report[['config']][['ppi']][['string']][['show_drugs']]
Show isolated nodes in the STRING network: r onc_enrich_report[['config']][['ppi']][['string']][['show_isolated_nodes']]

Complete network

visNetwork::visNetwork(
  onc_enrich_report[['data']][['ppi']][['string']][['complete_network']]$nodes, 
  onc_enrich_report[['data']][['ppi']][['string']][['complete_network']]$edges) |>
  visNetwork::visInteraction(multiselect = TRUE, tooltipDelay = 300) |>
  visNetwork::visIgraphLayout(layout="layout_nicely")

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No protein-protein interactions from STRING were found among members in the query set (with the required association score). Lowering the assocation score threshold of for interactions in STRING may provide a network. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

Network communities

visNetwork::visNetwork(
  onc_enrich_report[['data']][['ppi']][['string']][['community_network']]$nodes, 
  onc_enrich_report[['data']][['ppi']][['string']][['community_network']]$edges) |>
  visNetwork::visInteraction(multiselect = TRUE, tooltipDelay = 300) |>
  visNetwork::visIgraphLayout(layout="layout_nicely")

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No network communities were found among members in the query set (with the required association score). Lowering the assocation score threshold of for interactions in STRING may provide a network and associated communities. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

Network hubs

htmltools::br()
DT::datatable(onc_enrich_report[['data']][['ppi']][['string']][['hubscores']], 
              escape = F, extensions=c("Buttons","Responsive"), width = "100%",
              options=list(buttons = c('csv','excel'),dom = 'Bfrtip', pagelength = 20)) |>
  DT::formatStyle("symbol","hub_score", color = "white", backgroundColor = DT::styleInterval(onc_enrich_report[['config']][['disease']][['breaks']], onc_enrich_report[['config']][['disease']][['colors']]))

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No hubscores from the protein-protein interaction network were established for members in the query set (with the required association score). Lowering the assocation score threshold of for interactions in STRING may provide a network with hubscores. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

PPI network - BioGRID {.tabset}

The BioGRID network is expanded with n = r onc_enrich_report[['config']][['ppi']][['biogrid']][['add_nodes']] targets that are not part of the query set, but that interact with members of the query set
- These targets are selected based on the number of interactions that they have with members of the query set
Minimum evidence support required for each BioGRID interaction: r onc_enrich_report[['config']][['ppi']][['biogrid']][['minimum_evidence']]
Drugs added to the BioGRID network: r onc_enrich_report[['config']][['ppi']][['biogrid']][['show_drugs']]
Show isolated nodes in the BioGRID network: r onc_enrich_report[['config']][['ppi']][['biogrid']][['show_isolated_nodes']]

Complete network

visNetwork::visNetwork(
  onc_enrich_report[['data']][['ppi']][['biogrid']][['complete_network']]$nodes, 
  onc_enrich_report[['data']][['ppi']][['biogrid']][['complete_network']]$edges) |>
  visNetwork::visInteraction(multiselect = TRUE, tooltipDelay = 300) |>
  visNetwork::visIgraphLayout(layout="layout_nicely")

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No protein-protein interactions from BioGRID were found among members in the query set (with the required evidence support). Lowering the required evidence support for interactions in BioGRID may provide a network. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

Network communities

visNetwork::visNetwork(
  onc_enrich_report[['data']][['ppi']][['biogrid']][['community_network']]$nodes, 
  onc_enrich_report[['data']][['ppi']][['biogrid']][['community_network']]$edges) |>
  visNetwork::visInteraction(multiselect = TRUE, tooltipDelay = 300) |>
  visNetwork::visIgraphLayout(layout="layout_nicely")

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No network communities were found among members in the query set (with the required evidence support). Lowering the required evidence support for interactions in BioGRID may provide a network and associated communities. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

Network hubs

htmltools::br()
DT::datatable(onc_enrich_report[['data']][['ppi']][['biogrid']][['hubscores']], 
              escape = F, extensions=c("Buttons","Responsive"), width = "100%",
              options=list(buttons = c('csv','excel'),dom = 'Bfrtip', pagelength = 20)) |>
  DT::formatStyle("symbol","hub_score", color = "white", 
                  backgroundColor = DT::styleInterval(
                    onc_enrich_report[['config']][['disease']][['breaks']],                                                                                           onc_enrich_report[['config']][['disease']][['colors']])
  )

cat('<br>')
cat('\n <ul><li>  <i> <span style="font-size: 100%; padding: 3px; background-color:#989898; color:white">&nbsp;&nbsp;No hubscores from the protein-protein interaction network were established for members in the query set (with the required evidence support). Lowering the required evidence support for interactions in BioGRID may provide a network with hubscores. &nbsp;&nbsp; </span></i></li></ul>',sep='\n')
cat('\n')
cat('<br><br>')

{.unlisted .unnumbered .toc-ignore}

Citation Note : If you use the output of the Protein-protein interaction network module of oncoEnrichR in your research, please cite the following resources and tools as appropriate: