Slider controls the number of genes displayed on the network, based on their richness in canSAR annotation features. Highly annotated genes are ranked higher.

The default canSAR annotation feature selection (drug targets and ligandability likelihood assessed by the canSAR structural and chemistry ligandability pipelines) can be customised under the prioritization tab. Each selected feature contributes one point to the gene annotation score (except drug target which contributes 10 points).

Slider controls the minimum confidence level for an interaction to be displayed on the network. Interaction confidence ranges from 0 (no evidence) to 1 (highly confident).

By default only the following highly confident interactions are shown:

• Pathway signalling events
• Postranslational modifications
• Crystallographically resolved interactions

The confidence slider is activated when alternative interaction types are selected. These are evaluated according to the number of published evidence for the interaction. Each publication contributes 0.2 to the confidence score, making interactions with five or more publications highly confident (score of 1).

Predictive interactions (e.g. MSigDB TFT geneset-derived interactions) are given a default low score of 0.1.

The user can select from the different types of interactions in the canSAR interactome. Interactions can be classified by binding and information transfer mode. Interaction types are prioritised for display purposes.

Types:

• Reaction: Directional interaction where information is passed from enzyme to substrate via direct binding, resulting in a post-translational modification.
• Pathway: Directional interaction that can be activating or inhibiting. Usually information transfer occurs via direct binding though not always guaranteed.
• Direct: Direct binding between two proteins with no particular directionality in information transfer. Crystallographically resolved binding interfaces are highlighted as a separate group (PDB).
• Transcription: Directional interactions between a transcriptional modulator and its target gene. Transcriptional up-regulation and down-regulation is provided when known. By default indirect binding as the interaction occurs at the DNA level.
• Complex: Undirected interaction between two proteins in the sample complex, but not necessarily bound directly to each other. Low confidence complex interactions are treated as a separate group: these are mostly co-localisation based interactions, where the same complex assumption cannot be made.

To reduce network complexity, only a single interaction type is drawn between two genes on the network. Display prioritisation is based on information transfer and binding mode:

Reaction > Pathway (activation == inhibition) > Direct (PDB) > Direct > Transcription (upregulation == downregulation) > Transcriptional > Complex > Complex (low)

Selecting an interaction from the network reveals details for the specific interaction as well as all other interaction types that are not displayed in the Details tab.