Specify Query IDs and their organism - the only mandatory part
In the search box, insert a maximum of 100 IDs (Gene Symbols, UniProt IDs, or Entrez Gene IDs) in tab, newline or comma separated format. The search is case sensitive.
On the right, select the species the Ids are from - only one species is allowed (human is the default). It is also possible to decide if to retrieve all interactions of query proteins (e.g. querying for TP53 and BRCA1 will give all interactions of TP53 and of BRCA1) or all interactions among query proteins (e.g. querying for TP53 and BRCA1 will give only the interaction between TP53 and BRCA1 and the interactions of the proteins with themselves, if present).
Filter interactions by evidence (optional)
It is possible to select any (multiple choices accepted) of the acceptable PPI sources (i.e. experimental, predicted or orthology based interactions) and minimum threshold for experimental evidence: to improve the confidence of retrieved PPIs it is possible to filter out interactions that have been reported by less than one study and/or that have been discovered by only one method (e.g. using only mass spectrometry or only yeast two hybrid).
Filter interactions by context (optional)
It is possible to use any (multiple choices accepted) tissue, sub-cellular localization, diseases and druggability features to filter interactions, and decide if to retrieve PPIs present in any selected feature or only PPIs should present in all selected features (for example, if kidney and liver are selected, it is possible to retrieve interactions that are annotated with either kidney or liver, or only interactions that are annotated with both tissues). Filters can include both detailed and high level tissues. Brain detailed tissues as well as diseases are built as ontologies so it is possible to select either the parent term (and automatically all terms below) or one/some child terms. For example, a researcher might be interested in retrieving for the proteins of interest normal lung tissue interactions as well as lung cancer interactions, to compare networks from healthy and diseased state of lungs. The researcher would then have to input proteins in the search box, select 'lung' under tissue filter and then lung cancer in the disease ontology. This will allow to retrieve interactions that present one or the other annotation.
Each attribute selected for filtering will be visible in the results table, and the attributes will be available for enrichment analysis.
Specify PPI annotations to retrieve (optional)
It is possible to retrieve all annotations for interactions of interest specifying them in this field. PPIs will be annotated with all attributes from the selected categories (e.g., selecting 'sub-cellular localizations' will include all 13 available localizations as columns in the results table). Tissues, localization, disease and druggability attributes will be available for enrichment analysis.
In order to obtain topology measures, a researcher must have input one or more proteins in the search tab and clicked 'view results'. In the analyze topology panel, it is possible to retrieve degree, clustering coefficient and betweenness for each query protein and the retrieved interactors. These topology measures are calculated for each searched set of proteins and are not the global values for the same proteins if all IID would be considered.
To run this analysis, a researcher must have input one or more proteins in the search tab, selected one or more filters among tissues, localizations, diseases and druggability, and clicked 'view results'. Once the type of attribute to analyze is selected and 'run analysis' is clicked, the results will be displayed in a table. The output shows number of occurrences of that attribute in the retrieved network, number of occurrences in the whole interactome (comprising all PPIs in the same species and with the same evidence as the retrieved network. - e.g., if retrieved PPIs are human and supported by at least 2 bioassays, the interactome will be comprised of all such PPIs), p-value and adjusted p-value obtained by hypergeometric distribution calculation.
All tables obtained in the analysis tab are downloadable as CSV or Excel format.