Interaction - Methods summary

Summary

The Interaction resource presents interaction networks for 15216 genes based on protein-protein interaction data from IntAct, BioGRID, BioPlex and OpenCell that has been integrated with data related to protein expression, location and classification from the Human Protein Atlas. In addition AlphaFold 3 predicted 3D structures for the interactions present in more than one dataset (consensus) are displayed. The IntAct database relies on experimental molecular interaction data derived from literature curation or direct user submissions, the BioGRID contains curated data derived from publications, BioPlex contributes with interactions based on AP-MS experiments in HEK293T and HCT116 cells and OpenCell provides interaction data based on IP-MS experiments in CRISPR-edited HEK293T cells.

Key publications

Abramson J et al., Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature. (2024)
PubMed: 38718835 DOI: 10.1038/s41586-024-07487-w

Orchard S et al., The MIntAct project--IntAct as a common curation platform for 11 molecular interaction databases. Nucleic Acids Res. (2014)
PubMed: 24234451 DOI: 10.1093/nar/gkt1115

Oughtred R et al., The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions. Protein Sci. (2021)
PubMed: 33070389 DOI: 10.1002/pro.3978

Huttlin EL et al., The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell. (2015)
PubMed: 26186194 DOI: 10.1016/j.cell.2015.06.043

Cho NH et al., OpenCell: Endogenous tagging for the cartography of human cellular organization. Science. (2022)
PubMed: 35271311 DOI: 10.1126/science.abi6983

What can you learn from the Interaction Resource?

Learn about:

• the interaction partners of proteins
• the predicted 3D structures of consensus interactions
• the predicted and subcellular location of the proteins in the network
• the expression specificity of the proteins in the network
• the interaction partners expressed in the same cell type for genes with specific expression

Data overview

How has the data been generated?

Interactions included are direct interaction and physical associations with high and medium confidence from IntAct, physical multivalidated interactions from BioGRID, interactions with>75% probability from BioPlex and significant physical interactions from OpenCell. The consensus network plot consists of interaction pairs present in more than one of the datasets, but since BioPlex and OpenCell data is integrated in the IntAct database interaction pairs present only in IntAct and BioPlex or in Intact and OpenCell will not be shown in the consensus plot.

The predicted 3D protein structures have been generated in-house based on the AlphaFold 3 source code developed by Deepmind. The structure predictions were run on National Supercomputer Centre (NSC) at Linköping University.

The AI-system Alphafold is a machine learning approach in which the primary amino acid sequence and aligned sequences of homologues together with physical and biological knowledge about related protein structures are incorporated into the design of a deep learning algorithm to directly predict the 3D structure of a protein. Structure predictions have been made for consensus interaction pairs based on protein isoforms preferably mapped to UniProt identifiers, with a length between 6 aa and 4000 aa and containing exclusively standard amino acids.

All structures are displayed using the NGL Viewer.

Figure 1. Genes grouped by the number of first level consensus interaction partners

What is presented in the resource?

This resource presents interaction data for in total 15216 genes based on interactions for 12051 genes from IntAct, 11647 genes from BioGRID, 6374 genes from BioPlex and 4654 genes from OpenCell. The protein-protein interaction data on the gene pages is displayed as a network with nodes representing interaction partners and edges representing the number of datasets in which the interaction is present. The nodes can be coloured according to subcellular location based on data in the Subcellular resource, predicted location based on signal peptide and transmembrane region predictions, single cell type specificity based on RNA expression profiles or proteinclass, by using the highlight bar in the top of the plot. For genes classified as single cell type enriched or group enriched there is also an option to highlight interactors expressed in the same cell type. There is also an option for custom highlighting of 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 predicted 3D protein structures of consensus interactions can be explored by clicking on the blue points on the edges in the interaction networks and are displayed together with the corresponding PAE plots and predicted template modelling scores.