Enter IDs:

Maximum number of IDs: 5000 (response times may be slow with > 100 IDs)
Accepted IDs: Symbol (e.g., TP53), UniProt (e.g., P04637), Entrez Gene (e.g., 7157)

Select species where IDs are from:




Select retrieval strategy:


Select acceptable PPI sources:



Select minimum thresholds for experimental evidence





How should tissue filtering be applied?

How should localization filtering be applied?

How should disease filtering be applied?
Classes of proteins commonly targeted by drugs

Protein drug targets and their orthologs


How should drug filtering be applied?


Attributes selected for filtering will be shown in the results table. These attributes will be available for enrichment analysis.


Retrieved PPIs will be annotated with all attributes from the selected categories (e.g., selecting 'sub-cellular localizations' will include all 12 available localizations as columns in the results table). These attributes will be available for enrichment analysis.


Results

Select topology measures:




PPIs are not annotated with attributes that can be analyzed: tissues, localizations, diseases, druggability. Please specify some of these attributes in your query.

Numbers of interactions


Species Experimental Orthologous Predicted Total
alpaca 0 13 0 13
cat 0 296,308 0 296,308
chicken 399 223,386 0 223,701
cow 561 301,684 0 302,123
dog 59 292,826 0 292,857
duck 0 221,125 0 221,125
fly 62,249 51,916 0 111,975
guinea pig 0 294,510 0 294,510
horse 5 303,500 0 303,504
human 334,315 50,866 667,804 975,877
mouse 37,683 287,031 0 316,402
pig 76 300,884 0 300,945
rabbit 135 257,965 0 258,056
rat 6,929 276,002 0 281,909
sheep 3 289,985 0 289,986
turkey 2 201,945 0 201,947
worm 13,723 46,595 0 59,463
yeast 161,851 9,736 61,720 197,041
Total 617,990 3,706,277 729,524 4,927,742

What is IID?

IID is an on-line database of detected and predicted protein-protein interactions (PPIs) in 18 species including human, 5 model organisms, and 12 domesticated species. In each of these species, it can provide networks that are specific to tissues, sub-cellular localizations, diseases, and druggable proteins.


What makes IID different from other interaction databases?

  • the only database with context-specific networks for the common model organisms and domesticated species
  • provides the most comprehensive interaction networks for most of these species by integrating:
    • experimentally detected PPIs from 9 curated databases (BioGRID, IntAct, I2D, MINT, InnateDB, DIP, HPRD, BIND, BCI)
    • orthologous PPIs
    • high-confidence PPIs predicted by state-of-the-art computational methods (Rhodes, Nat. Biotech., 2005; Elefsinioti, Mol. Cell Proteomics, 2011; Zhang, Nature, 2012; Kotlyar Nat. Methods, 2015)
  • provides one of the largest selections of human context-specific networks (and the largest selections for most of the other included species)
    • networks can be specific to tissues, sub-cellular localizations, diseases, and druggability status - or any combination of these conditions
    • human networks are available for 120 tissues, including extensive options for brain and joint-related tissues

What organisms are in IID?

IID includes interactions for 18 species:

  • human (H. sapiens)
  • 5 model organisms: fly (D. melanogaster), mouse (M. musculus), rat (R. norvegicus), worm (C. elegans), and yeast (S. cerevisiae)
  • 12 domesticated species: alpaca (V. pacos), chicken (G. gallus), cat (F. catus), cow (B. taurus), dog (C. familiaris), duck (A. platyrhynchos), guinea pig (C. porcellus), horse (E. caballus), pig (S. scrofa), rabbit (O. cuniculus), sheep (O. aries), turkey (M. gallopavo)


Citation

Kotlyar M, Pastrello C, Malik Z, Jurisica I. IID 2018 update: context-specific physical protein-protein interactions in human, model organisms and domesticated species. Nucleic Acids Res. 2019;47(D1):D581-D589. doi:10.1093/nar/gky1037


Contact Us

iid@ai.utoronto.ca

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.





Analysis

Analyze topology

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.



Analyze PPIs

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.