As the data accumulated in the IntAct database continues to grow and user requirements become more complex, a new website has been developed to meet the demands of an increased content load and to provide richer functionalities for searching, browsing and visualizing molecular interaction data. Some fundamental changes have been made in the way we present data, central to which is the initial presentation of the data as a list of binary interaction evidences. Users may now access the individual evidences that describe the interaction of two specific molecules, thus allowing users to filter result sets (e.g. by interaction detection method) to only retain user-defined evidences. For convenience purposes evidence pertaining to the same interactors are grouped together in the binary interaction evidence table.
In order to improve navigability, we have reorganized the layout of the website and grouped functionality in tabs enabling rapid access to specific sections of the web site. The following sections reflect the tabs available.
The home page provides general documentation, a simple search facility and a featured dataset of the month. The dataset of the month is usually emphasising a recent publication with directly submitted data, or a group of related publications curated in our targeted curation projects. The side bar menu gives easy access to both data and software downloads, documentation and statistics.
In addition to a simple Google-like text search facility, the IntAct website allows the use of the Molecular Interaction Query Language (MIQL) (Aranda et al., in preparation) to search data. This provides a set of predefined fields that can be combined, enabling the creation of complex queries via use of boolean logic. Users can use and combine these fields manually in the search field. Additionally, one can get assistance by opening the Advanced Field search and accessing a list of existing fields and, where appropriate, a list of existing values (e.g. datasets, expansion methods). Upon adding fields to the current query, the list of resulting interactions gets updated.
More specialized searches can be accessed from the search tab. Users can now search for interactors that are annotated with terms from the Gene Ontology (19
), InterPro, ChEBI and the UniProt Taxonomy, or interactions described using specific terms from the PSI-MI controlled vocabularies. Relevant suggestions are displayed while the user is typing a term name. Selecting a term in the suggestion list will display the matching set of interactions in the corresponding tab.
As IntAct now contains a growing set of interaction involving chemical compounds, a dedicated search module allowing users to search by chemical structure has been developed in collaboration with the ChEBI team. By drawing a chemical structure in the provided applet (requires a Java enabled browser), one can search for matching (exact, by similarity or substructure) molecules involved in IntAct interactions. Once the drawn structure is submitted, a matching list of molecules is displayed, each of which can then be selected to display interactions involving this compound.
Once a query has been submitted to the website, the ‘Interactions’ tab automatically opens and presents the list of interactions matching the query (). This table can be customized by clicking on the button ‘Change columns displayed’ in the table header so that one can choose the columns to be shown. When a large number of interactions match the query, the table will only show 30 interactions at a time and the user can browse subsequent pages using the navigation items in the table header. If the queried dataset contains spoke expanded interactions, a message will inform the user (above the table) and give the opportunity to easily filter these out. Should users wish to download a given dataset, it is possible to select one of the standard format such as PSI-MI XML or MITAB from the table header’s drop down menu and click on the export button to retrieve a data file.
Figure 1. The figure shows the interactions found after searching for Pubmed 16525503. Each row corresponds to one binary interaction with a list of evidences. Only the evidences matching the search criteria are shown in the results. In September 2009, 24 binary (more ...)
Clicking the magnifying glass in the far left-hand column will show to the user the detailed content of each interaction, which is explained in the section Interaction Details below.
Each participating molecule contains its ‘Links’ column, that contains the clickable logos to navigate to the main external resource about this molecule (e.g. UniProtKB or ChEBI). For proteins, a Dasty2 (20
) logo can be clicked to navigate to the ‘Molecule View’ tab, explained below.
One of the new features of the website is the possibility of browsing result sets by selected topics. The different options are classified in groups, according to the participant molecule type: Proteins, Chemicals, or Nucleic Acids.
Based on the UniProt Taxonomy or Gene Ontology annotation of protein interactors, the current result set can be analysed/refined using a hierarchical display of ontology terms and the numbers of matching interactions in the current result set (Supplementary Figure S3
). Other options link to external sites, and allow the visualization of InterPro domains, the involvement of molecules in Reactome pathways, the chromosomal location of the originating gene in Ensembl, or links to mRNA expression with ArrayExpress (21
). To avoid overloading external sites, the number of molecules that IntAct uses in the links has been globally reduced to 200. When this happens, a corresponding warning message is shown so the user can either choose to narrow the result set or browse through the first 200 results.
For chemicals, the ChEBI ontology browser is available, which classifies the interactors according to Chemical Ontology terms such as role, molecular structure or subatomic particle.
The aim of the ‘Lists’ tab is to display the list of participants involved in the interactions from the result set. The molecules are classified by type. For each type, a table is shown listing the participants with selected attributes, such as the originating species or a description (Supplementary Figure S4
). Depending on the molecule type, different actions can be performed using a custom selection of participants from the table. Most of the available options link to external sites using cross references as in the ‘Browse’ tab. This view also allows to expand the current result set, selecting some or all of the current interactors, and then searching all interactions these interactors participate in. From this view, it is possible to select specific molecules and search for the interactions in which they participate.
The interaction detail tab only becomes active when a single interaction has been selected from the interaction tab. This view shows the details of a given interaction and features additional manually annotated information, such as the binding domains, tags, and/or stoichiometry of the participants (Supplementary Figure S5
From here it is possible to find ‘similar’ interactions (i.e. interactions in which one or more of the participants of the interaction of interest have been also reported to interact). This may, for example, give additional evidence of the existence of a complex, suggest the architecture of a complex at the binary level, or give further interactions made by either a complex as a whole or by its components. The similar interactions are shown in a matrix where the columns are the participants and the rows are the interactions ().
The figure explains the ‘Find similar interactions’ matrix, which is accessible from the Details page.
In the tables from the ‘Interactions’ and ‘Lists’ views, clicking on the Dasty2 logo that can be found adjacent to protein molecules will redirect the user to the ‘Molecule View’ tab (see Supplementary Figure S6
). Using the DAS protocol (22
), this view shows protein features projected onto its sequence and, where available, its structure. It combines external data from UniProtKB, PDB, InterPro, among others, with IntAct data on e.g. interacting domains. Thus it is possible to obtain a visualization of, for example, an IntAct-annotated binding domain, its overlap with an InterPro domain and the localization of both features on a PDB structure, although none of the involved databases alone contains all the relevant data.
One of the most popular features of interaction databases is the rendition of a graphical network derived from a selected set of interactions. IntAct provides a simple static graph under the ‘Graph’ tab, but interoperability with external visualization tools, such as the open source tool Cytoscape (23
), has now become a priority. This has been made easily possible by the use of the PSI-MI standards by both IntAct and Cytoscape. Cytoscape can be started directly from within the IntAct website by clicking on the Cytoscape icon in the ‘Graph’ tab. The first time this is done it may take some time while the application is automatically downloaded and started. The ‘Graph’ tab is only active when the result set is relatively small (the current limit is set at 300 binary interactions) to avoid the complications related to data visualization of big networks. On the left-hand side, this view shows a simple representation of the network, where each line represents an interaction between two molecules. On the right of the page, the link to start Cytoscape on the fly using Java WebStart can be found.
Larger networks can be visualized by using a local installation of Cytoscape and exporting the interactions of interest using the Export but the ‘Interactions’ tab.