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What is this view?

Binary interactions

In this tab, we display the list of interactions that you have selected using one of our search features. Despite the fact that our data are annotated to accurately reflect the interactions reported in scientific literature, the data is shown in this view as binary interactions. Whenever the data was reported as a co-complex involving more than two molecules, we store it as such in the IntAct database and post-process it so the portal can show it as binary interaction. This post-processing is the Spoke Expansion model (connects bait to all preys):



sourceExp

At any moment you can choose to display the expansion column in this view in order to see which interaction are spoke expanded and which are not.

Description of what has changed

  • We have added more download options to allow users to retrieve their interaction set using more standard formats such as PSI-MI XML and PSIMITAB (version 2.5, 2.6 or 2.7) but also XGMML, RDF and Biopax (level 2 and 3).
  • We have now four different table views : minimal(molecule names and interaction AC), basic (minimal + molecule links, interaction detection method, negative), standard(minimal + molecule species, confidences, publication details, experiment details), expanded (standard + more experiment details) and complete (all mitab 2.7 columns).

Configuring the view to your need"

In the header of the interaction table you will find a button: ‘Change Column Display’ that will show you all the columns/Table views available and allow you to update the current selected set.

Downloading the data into Standard formats"

In the header of the interaction table you will find a drop down list that contains all the formats currently supported when downloading the interaction data. Select one of them and click the export button next to the list. Please note that PSI-MI XML is only available when the interaction set is no bigger than 1000 interactions.

Opening the interaction details"

Clicking on the magnifying glass in the first column of the interaction table will open the details of the corresponding interaction in the Interaction Details tab, giving you access to more details of the manually curated record.

What is this view?

Browsing (Browse Tab)

This tab is meant to give you access to more content based on the currently selected set of interactions. Please note that linking to third party resources will only include up to 200 molecules , if you exceed this number you will see the warning icon (This number has been reduced to 125 molecules for mRNA expression). Now let’s look at the features available to you:

Limiting the scope of the current dataset with the Uniprot Taxonomy ontology

Allows users to browse the Uniprot Taxonomy hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Limiting the scope of the current dataset with the GO ontology

Allows users to browse the GO hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Limiting the scope of the current dataset with the ChEBI ontology

Allows users to browse the ChEBI hierarchy as a tree and select terms in order to narrow down their dataset. Once a term is selected, you are taken back to the interaction tab to review your dataset.

Bulk linking to third party resources by using involved proteins

  • Proteins by Reactome pathway: Sends your proteins to the Reactome SkyPainter that will show you the pathways in which these molecules are know to play a role.
  • Proteins by Chromosomal location: Sends your list of proteins to Ensembl’s Karyotype viewer and overlays the proteins on the chromosomes.
  • Proteins by mRNA expression: Sends your set of proteins to the ArrayExpress Atlas that will show the known gene expression based on experimental studies.
What is this view?

Searching Interactions (Search Tab)

As you can see in this tab we are now trying to give you more targeted choice to do your queries, please note that the examples provided in this tab are live links so you can simply click them to see the resulting interactions sets.

Using the Quick Search

In this search panel you are free to type anything that might relate to interactions, whether it is properties of their interactor (gene name, identifiers, GO term…) or more specific to the interaction like publication, authors, experimental detection method, ...

Some examples:

  • Try the query: imatinib
    This is a drug for which we have curated a number of interactions.
    Once you press the search button you should be taken to the Interaction Tab that lists 130 binary interactions.
    If you want to construct more complex queries we recommend you take a look at the Molecular Interaction Query Language, accessible from the quick search panel.
  • Try the query: species:yeast AND type:"direct interaction"
    This query selects all interactions involving yeast interactors that have been shown to have direct interactions. If you customize the column display of the interaction tab, you will see that not only “direct interaction” have been selected but also children terms in the PSI-MI ontology.

Using the Ontology Search

Open the Rearch Tab. This panel is specialised to give you an easy access to ontology search. So far you can search on 4 ontologies:

  • Gene Ontology
  • InterPro
  • PSI-MI
  • ChEBI

Whenever you start typing a query in this search panel, the system will search as you type and propose a list of matching controlled vocabulary terms. You can then select one of them and select matching interactions.

For example, type: cancer
You will be presented with a few choices, please note that each term is followed by the count of matching interactions in the IntAct database.

Select a term with the mouse or using the keyboard cursor keys and you will be taken to the interaction tab.

Searching the Compound chemical structure

In this panel you will be able to draw all or part of a chemical structure and search for chemical compounds. If you get any matched, you can then see all interactions involving them.

First you have to open up the chemical search panel so that the applet can load, it might take a few seconds. Then you can start drawing your structure, for instance:

Once you have drawn your structure, select Similarity and press Search. You should be presented with a list of matching compound. Now choose one molecule and click the link: IntAct interactions. You will be taken to the interaction tab to review the data.

Complex Expansion

Binary interactions generated by co-complex expansion

Why should you care about complex expansion ?

Some experimental methods such as Tandem Affinity Purification do generate molecular interactions that can involve more than 2 molecules. Despite the fact that IntAct curation team do capture the molecular interaction as they were reported in the corresponding experiment, when you search using the intact web site, the results of your query is always shown as set of binary interactions (i.e. 2 molecules). We would like to draw your attention on the fact that whenever the reported interaction was a co-complex we do apply an expansion algorithm that transform this n-ary interaction into a set of binary interactions. While none of these agorithms is perfect and will very likely generate some false positive interactions, it is useful to present the data in a consistent manner. Bear in mind that we will strive to differentiate in the search results which interactions are a real experimental binary from expanded ones.

Existing expansion algorithm

There are several known algorithm allowing to transform an n-ary interaction into a set of binaries. The illustration below present the two well known expansion model and illustrates why they can be incorrect.



sourceExp

  • Spoke expansion: Links the bait molecule to all prey molecules. If N is the count of molecule in the complex, it generated N-1 binary interactions.
  • Matrix expansion: Links all molecule to all other molecule present in the complex. If N is the count of molecule in the complex, it generated (N*(N-1))/2 binary interactions.

Now the issue (as illustrated at the bottom right of the diagram above) with these two models lies in the fact that the real complex might not be articulated around the experimental bait but instead, this bait might be linked to a smaller complex, hence most binary interaction generated by spoke and matrix expansion result in false positive.



PSICQUIC

How is the number of interactions in other databases obtained?

PSICQUIC is a standard way to access molecular interaction databases across which it repeats the same query. The number of databases providing data may vary, depending on the status of their services and only those that are active are used in this query. By clicking on the number of interactions you will be redirected to the PSICQUIC View, where you can browse the results in those other resources.

The services currently active are:

Check the PSICQUIC site for more information.

IMEx

What is the significance of the IMEx dataset?"

IMEx is a network of databases which have agreed to supply a non-redundant set of data expertly manually annotated to the same consistent detailed standard which, as such, represents a high-quality subset of the data each individually provides. The number of databases providing data may vary, depending on the status of their services and only those that are active are used in this query. By clicking on the number of interactions you will be redirected to the IMEx View, where you can browse the results in those other resources.

The services currently active are:

Check the IMEx site for more information.

What is this view?

Representation of Experimental Features

This section shows the graphical representation of experimental features, where each participant is represented as a white rectangle with a black border and a line for each hundredth amino acid. All available features are attached to their associated participant and their categories are represented in the right side of the legend. The left side of the legend dynamically shows the range statuses occuring in the shown interaction. These are the possible range statuses:

sourceExp

Interacting with the widget

Hover over a feature to see more information in a tooltip.
sourceExp

To display a single interacting region click on it and click again to display all interacting regions.
Displaying all interacting regionsDisplaying one interacting region
sourceExpsourceExp
What is this view?

Dynamic molecular interaction data

This section shows the graphical representation of dynamic molecular interactions. By default it displays all the interactions from one experiment using radio buttons to allow users to highlight interactions in different variable conditions.

Datasets

Curated datasets are publications tagged, either computationally or manually by a curator, as being relevant to a specific area of biology. These are actively maintained and grow with every release.
New datasets can be requested, if relevant to your work, by mailing intact-help@ebi.ac.uk.

Manually selected datasets

  • Affinomics - Interactions curated for the Affinomics consortium. PSI 2.5

    This dataset contains interactions which have been derived in the context of the EU Affinomics project (Grant number 241481). This comprises interactions directly submitted by the consortium partners as well as interaction derived from the literature. The current focus is on interactions derived by Proximity Ligation Assay (MI:0813), a method pioneered by the group of consortium partner Ulf Landegreen.

  • Alzheimers - Interaction dataset based on proteins with an association to Alzheimer disease. PSI 2.5

    The compilation of this dataset and its curation was carried out in collaboration with Perreau V.M. University of Melbourne, Australia. Interactions were investigated in the context of Alzheimers disease with a particular focus on APP (A4) protein. The articles to be curated were determined based on protein annotations and literature scanning.

    Publications based on this dataset: PMID: 20391539

  • BioCreative - Critical Assessment of Information Extraction systems in Biology. PSI 2.5

    The Biocreative dataset is a large dataset of curated publications from the Journal of Biological Chemistry (2006) and Nature publishing house which were manually curated by IntAct curators. This dataset has been used in BioCreative II (Critical Assessment of Information Extraction systems in Biology): Protein-Protein Interaction Task . The protein-protein interaction task focused on the prediction of protein interactions from full text articles, which are represented in the Biocreative dataset. The Biocreative dataset provided by IntAct is a resource for text mining development and testing. The data file (source-text.txt) that provides a mapping between IntAct interactions and the sentence(s) of the publication that allowed an IntAct curator to identify the interaction is available here.

    Publications based on this dataset: PMID: 18834496, 18834487, 19208158

  • Cancer - Interactions investigated in the context of cancer. PSI 2.5

    This dataset consists of interactions of proteins that are involved in cancer. An ongoing literature survey was carried out to determine publications of interest. Protein annotations were also considered when choosing the publications to be curated.

  • Cardiac - Interactions involving cardiac related proteins. PSI 2.5

    A collection of interactions relating to proteins identified as associated with the cardiovascular system. These annotations create a PPI network which can be used to advance the understanding of protein interactions within the cardiovascular system. The gene lists have been assembled by the Cardiovascular Gene Annotation group at the University College, London and the dataset has also largely been assembled by that group, funded by the British Heart Foundation grant RG/13/5/30112, with the help of IntAct curators located at the EBI. This work is a collaboration with the Cardiac Proteomics and Signalling Laboratory at UCLA, funded by NHLBI Proteomics Center Award HHSN268201000035C.

  • Chromatin - Epigenetic interactions resulting in chromatin modulation. PSI 2.5

    Chromatin relevant protein-protein interaction studies have been curated by IntAct curators from peer reviewed literature. These comprise interactions which are involved in modulating, modifying or forming chromatin. This dataset aims at capturing major epigenetic interactions resulting in chromatin modulation. Most of the publications were derived from 'Chromatin Papers ListServe' maintained by Bone J.

  • Coronavirus - Interactions investigated in the context of Coronavirus. PSI 2.5

    Dataset of molecular interactions extracted from publications involving viral proteins from the Coronaviridae family and human proteins, along with a certain proportion of other model organisms. The data features mostly protein-protein and some RNA-protein interactions and covers SARS-CoV2 and SARS-CoV primarily, with some interactions from other members of Coronaviridae as well. Interactions between human proteins relevant for SARS-CoV2 infection have also been included.

  • Crohn's disease - Interactions of proteins identified as having a link to Crohn's disease. PSI 2.5

    Interactions extracted from publications focused on proteins involved in Crohn's disease.

  • Cyanobacteria - Interaction dataset based on Cyanobacteria proteins and related species. PSI 2.5

    This dataset was obtained in a collaboratice effort with Franck Chauvat, Corinne Cassier-Chauvat, Jean-Cristophe Aude, Magali Michaut, and Pierre Legrain from DBJC, CEA Saclay, Gif-Sur-Yvette, France. Cyanobacteria like Synechocystis sp. can be used as model organism as they undergo both oxidative respiration and photosythesis. Cyanobacteria have many features common to bacteria including a lack of compartmentalisation. This dataset is used to gather articles showing interactions relevant to plant photosynthesis, redox metabolism, resistance to metal and oxidative stress. Most interactors belong to Cyanobacteria species, with a focus on Synechocystis sp. (strain PCC 6803), TaxID 1148, but some interactors belong to species where biological events seen in Cyanobacteria may also occurs like plants for photosynthesis. Also, the dataset contains a number of hybrid experiments using electron transfer between proteins from different species.

    Publications based on this dataset: PMID: 18508856

  • Diabetes - Interactions investigated in the context of Diabetes. PSI 2.5

    This dataset consists of interactions of proteins that are involved in diabetes.

  • Huntington's - Publications describing interactions involved in Huntington's disease. PSI 2.5

    Interactions extracted from publications focused on proteins involved in Huntington's disease.

  • IBD - Inflammatory bowel disease PSI 2.5

    Interactions extracted from publications focused on proteins involved in Inflammatory Bowel Disease.

  • Neurodegeneration - Publications depicting interactions involved in neurodegenerative diseases PSI 2.5

    Interactions extracted from publications focused on proteins involved in neurodegenerative diseases.

  • Parkinsons - Interactions investigated in the context of Parkinsons disease PSI 2.5

    Interactions were investigated in the context of Parkinsons disease with a particular focus on LRRK2 protein and were derived in the context of the The Michael J. Fox Foundation for Parkinson's Research LRRK2 Biology LEAPS Award 2012.

  • Rare diseases - Interactions investigated in the context of Rare genetic disease PSI 2.5

    This is a dataset of molecular interactions extracted from publications focused on the study of any rare disease. 'A rare disease' is defined according to the European Union Regulation on Orphan Medicinal Products (1999): a disease that affects not more than 1 person per 2000 in the European population. The dataset is enriched with experimentally proven impact of clinical mutations on interactions, and also with the non-clinical mutations which are found to have effect on protein functionality.

  • Ulcerative colitis - Interactions of proteins identified as having a link to ulcerative colitis PSI 2.5

    Interactions extracted from publications focused on proteins involved in ulcerative colitis.

Computationally maintained datasets

These datasets are computationally maintained but additional papers may be manually added to this set by a curator during the curation process. When datasets are computationally added to a publication, the large scale papers (more than 100 interactions per experiment) are excluded.

  • AFCS - Interactions from the Alliance for Cell Signaling database PSI 2.5

    This dataset was obtained from the Alliance for Cell Signaling database. The Alliance of Cellular Signalling (AFCS) consisted of around 20 institutions which were engaged in a collaborative effort to investigate and understand cellular signalling networks (http://www.afcs.org/). The AfCS used high-throughput methods to detect protein-protein interactions between signaling molecules expressed in B cells and cardiac myocytes. The AfCS arranged a collaboration with Myriad Genetics to perform large-scale yeast two-hybrid screens. IntAct acted as a data repository of protein-protein interaction data generated by the AFCS project.

  • Apoptosis - Interactions involving proteins with a function related to apoptosis PSI 2.5

    Datasets of apoptosis relevant protein-protein interaction studies are curated by IntAct curators from peer reviewed literature. These datasets are a resource for biologists seeking to understand protein interaction networks and cell death. Small-scale interactions involving proteins annotated with the GO terms "Apoptosis" are included in this set.

  • Archaea - Interaction dataset based on Archaea proteins PSI 2.5

    Archaea are phylogenetically very different from Bacteria and Eukarya and show many differences in their biochemistry from other forms of life. This was considered of interest and peer reviewed literature that is curated is scanned for interactions involving proteins from this group.

  • PDBe - Data obtained from the Protein Data Bank Europe PSI 2.5

    The Protein Data Bank in Europe (PDBe) is the European project for the collection, management and distribution of data about macromolecular structures, in collaboration with Worldwide Protein Data Bank (wwPDB). IntAct has incorporated a subset of the data from this database involving heterodimeric protein interactions.

  • NDPK - Interactions involving proteins containing InterPro domain IPR001564, Nucleoside diphosphate kinase, core. PSI 2.5

    NDPKs, which play a major role in the synthesis of nucleoside triphosphates other than ATP, also possess other enzymatic activities and are required for cell proliferation, differentiation and development.

    Publications based on this dataset: PMID: 19415463

  • Synapse - Interactions of proteins with an established role in the presynapse. PSI 2.5

    This dataset has been created for proteins-protein interactions involving at least one protein with an established link to the synapse. The list of human, rat and mouse gene names used for computationnally maintaining this dataset are available here. Interactions made by orthologous proteins have been added manually by IntAct curators.

  • Virus - Publications including interactions involving viral proteins. PSI 2.5

    The MINT and HPIDb databases are major contributors to this dataset.

Species-based datasets

Species specific datasets are generated from the protein-protein interaction data curated from peer reviewed journals and are available here. The data are based on the taxonomy of the proteins taking part in the interaction. Analysis of one such dataset, which involved Arabidopsis proteins has been discussed in PMID: 20371643.

Mutations influencing interactions dataset:

Download

The latest mutation dataset is available here: mutations.tsv

Introduction

This dataset is the result of the deep-curation policies used within the IMEx Consortium and it provides a set of protein sequence changes (mutations) and their effect over interaction outcome. The information given in the dataset expands the information that can be found in the "Feature(s) interactor A/B" columns in the PSI-MITAB 2.7 standard format and within the attribute "feature" in PSI-MI-XML format.

Dataset description

This dataset contains over 28,000 instances where mutations have been experimentally shown to affect a protein interaction. There are several types of mutations covered, the terms used have been described in the PSI-MI controlled vocabularies, accessible at www.ebi.ac.uk/ols4/ontologies/mi:

  • Mutation (MI:0118): A change in a sequence or structure in comparison to a reference entity due to a insertion, deletion or substitution event. This root term is used when there is a mutation present in a protein and the wild type version has not been tested or shown to interact in the referenced paper.
    • Mutation causing an interaction (MI:2227): A change in a sequence or structure in comparison to a reference entity due to a insertion, deletion or substitution event that enables an interaction when compared with the wild-type, which does not interact.
    • Mutation decreasing interaction (MI:0119): Region of a molecule whose mutation or deletion decreases significantly interaction strength or rate (in the case of interactions inferred from enzymatic reaction).
      • Mutation decreasing interaction rate (MI:1130): Region of a molecule whose mutation or deletion decreases significantly interaction rate (in the case of interactions inferred from enzymatic reaction).
      • Mutation decreasing interaction strength (MI:1133): Region of a molecule whose mutation or deletion decreases significantly interaction strength.
      • Mutation disrupting interaction (MI:0573): Region of a molecule whose mutation or deletion totally disrupts an interaction strength or rate (in the case of interactions inferred from enzymatic reaction).
        • Mutation disrupting interaction rate (MI:1129): Region of a molecule whose mutation or deletion totally disrupts an interaction rate (in the case of interactions inferred from enzymatic reaction).
        • Mutation disrupting interaction strength (MI:1128): Region of a molecule whose mutation or deletion totally disrupts an interaction strength.
    • Mutation increasing interaction (MI:0382): Region of a molecule whose mutation or deletion increases significantly interaction strength or rate (in the case of interactions inferred from enzymatic reaction).
      • Mutation increasing interaction rate (MI:1131): Region of a molecule whose mutation or deletion increases significantly interaction rate (in the case of interactions inferred from enzymatic reaction).
      • Mutation increasing interaction strength (MI:1132): Region of a molecule whose mutation or deletion increases significantly interaction strength.
    • Mutation with no effect (MI:2226): A change in a sequence or structure in comparison to a reference entity due to a insertion, deletion or substitution event that does not have any effect over an interaction when compared with the wild-type.

Output format description

We provide a tab-delimited flatfile download with the full dataset. Every instance of a mutation affecting a given interaction is given a unique identifier (“Feature AC”). Please notice that some mutations will affect more than one residue position range in non-consecutive order. Each one of these non-consecutive ranges is recorded in a separate line, hence there will always be a difference between the number of lines in the file and the number of unique mutations. Here is a brief description of the different columns used in the file:

  • Feature AC: Accession number for that particular mutation feature.
  • Feature short label: Human-readable short label summarizing the amino acid changes and their positions, compliant with the Human Genome Variation Society recommendations (see http://varnomen.hgvs.org/recommendations/protein/) .
  • Feature range(s): Position(s) in the protein sequence affected by the mutation.
  • Original sequence: Wild type amino acid residue(s) affected, in one letter code.
  • Resulting sequence: Replacement sequence (or deletion) in one letter code.
  • Feature type: Mutation type, following the PSI-MI controlled vocabularies as stated above.
  • Feature annotation: Specific comments about the feature that can be of interest.
  • Affected protein AC: Affected protein identifier (preferably UniProtKB accession, if available).
  • Affected protein symbol: As given by UniProtKB.
  • Affected protein full name: As given by UniProtKB.
  • Affected protein organism: TaxID and species name as given by UniProtKB.
  • Interaction participants: Identifiers for all participants in the affected interaction, along with their species and molecule type between brackets.
  • PubMedID: Reference to the publication where the interaction evidence was reported.
  • Figure legend: Reference to the specific figures in the paper where the interaction evidence was reported.
  • Interaction AC: Interaction accession within our databases. This can be used to obtain further information about the interaction.

Further columns will be added once the dataset is enriched with cross-references to other databases such as UniProt and Ensembl.

Mutations dataset format example

Feature AC Feature short label Feature range(s) Original sequence Resulting sequence Feature type Feature annotation Affected protein AC Affected protein symbol Affected protein full name Affected protein organism Interaction participants PubMedID Figure legend Interaction AC
EBI-1203484 p.Asp3702_Tyr3703delinsAlaAla 3702-3703 DY AA mutation decreasing strength(MI:1133) uniprotkb:P20659 TRX Histone-lysine N-methyltransferase trithorax (EC 2.1.1.43) (Lysine N-methyltransferase 2A) 7227 - Drosophile melanogaster (Fruit fly) uniprotkb:P20659 (protein, 7227 - Drosophile melanogaster (Fruit fly)) 10656681 5A EBI-1203452
EBI-709274 p.Leu152Glu 152-152 L E mutation decreasing(MI:0119) uniprotkb:O43521 B2L11 Bcl-2-like protein 11 (Bcl2-L-11) (Bcl2-interacting mediator of cell death) 9606 - Homo sapiens uniprotkb:O43521(protein, 9606 - Homo sapiens);uniprotkb:P97287(protein, 10090 - Mus musculus) 15694340 EBI-709266
EBI-10762087 p.Pro116_Gly117insXaa 116-117 PG PXG mutation(MI:0118) comment:Feature - insertion of crosslinkable amino acid p-benzoyl-L-phenylalanine (pBpa) uniprotkb:P69411 RCSF Outer membrane lipoprotein RcsF 83333 - Escherichia coli (strain K12) uniprotkb:P69411 (protein, 83333 - Escherichia coli (strain K12));uniprotkb:P0A940 (protein, 83333 - Escherichia coli (strain K12)) 25525882 Fig. 2C Supp Fig.3D EBI-10761554