Interaction - Methods summary

Summary

The Interaction Section contains information about human protein-protein and metabolic interaction networks. The protein-protein interaction networks are based on data from the EMBL-EBI IntAct database that relies on experimental molecular interaction data derived from literature curation or direct user submissions. The metabolic interaction network contains information on the genes that encode for human metabolic reactions. The network has been constructed in silico, and is the result of experiments whose data has been deposited in a wide range of databases and has references to around 2900 different articles and books.

Key publications

Orchard S et al. (2014) "The MIntAct project - IntAct as a common curation platform for 11 molecular interaction databases." Nucleic Acids Research, 42(Database issue):D358-63

Robinson JL et al. (2020) "An atlas of human metabolism" Sci Signal. 12 (624): aaz1482

What can you learn from the Interaction Section?

Learn about:

• the interactions of a protein with other proteins
• features of the protein-protein interaction networks
• what pathways/subsystems a metabolic gene is part of
• which genes are nearby in the metabolic network
• how the expression of the genes in a pathway/subsystem varies across different tissues

How has the data been generated?

The protein-protein interaction data selected from the IntAct database are protein pairs that have at least one interaction classified as direct interaction or physical association and where both proteins belong to the ensembl gene set in the Human Protein Atlas. The set of interactions have also been filtrated based on the MI score which is set for all interactions in IntAct. The MI score is based on detection method, interaction type and number of publications reporting the interaction, and only interactions with score >0.45 are presented.

The human metabolic network, Human-GEM, is the most recent development in a series of genome-scale metabolic models. Thus, Human-GEM integrates previously developed metabolic networks (Figure 2), reconciling information such as gene-reaction associations. Since the first public release in August 2018, Human-GEM has reached version 1.10.0 in its 39th release in September 2021.

Figure 2. The evolution of the human metabolic networks by publication year, with arrows indicating incorporation or reconciliation.

What is presented in the section?

The protein-protein interaction data on the gene pages is displayed as a network with nodes representing interaction partners and edges representing the interaction type and the confidence level of the MI score for the interaction. The type of interaction (direct interaction or physical association) is reflected by the colour of the edges, while the confidence of the interaction is reflected by the thickness of the edges with scores larger than 0.6 (high confidence) having a thicker line and those with score 0.45-0.6 (medium confidence). The nodes can be coloured according to subcellular location based on data in the Subcellular section, predicted location based on signalpeptide and transmembrane region predictions, tissue specificity based on RNA tissue expression profiles or proteinclass, by using the highlight bar in the top of the plot. There is also an option to highlight nodes using the top left Filter option in which a query can be built to for example label all nodes that are tissue enriched in both human and mouse brain or belongs to a certain tissue expression cluster.

The metabolic part presents gene information in 3 parts: general information, a metabolic summary table, and the pathway map. The general information includes the gene description, protein class, and other Human Protein Atlas information. In the metabolic summary table, the gene-reaction association is combined with reaction-subsystem associations and reaction-metabolite-compartment associations to deliver two key insights: what pathways/subsystems the gene contributes to, and in which cellular compartment(s) the associated reactions are expected to take place based on metabolite information. The size of the respective pathways are also included next to the number of reactions the gene catalyzes. The interactive part of the page is shown after clicking on a pathway in the metabolic summary table: the associated metabolic network map is shown, together with a gene-tissue heatmap that shows the expression of genes in that pathway among different tissues.