IntAct

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):

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.

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.

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.

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.

• 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.

How is the number of interactions in other databases obtained?

What is the significance of the IMEx dataset?"

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:

Interacting with the widget

Displaying all interacting regions	Displaying one interacting region

Dynamic molecular interaction data