Cell-Cell Interaction Database

Overview

This page describes the automated construction of a cell-cell interaction database by filtering existing curated protein-protein interaction (PPI) data. Cell-cell interactions are important for understanding tissue organization. We and others have built cell-cell interaction databases (1-5). The resource available from this website represents an automatically built set of protein-protein interactions that can mediate cell-cell communication that is expanded compared to previous databases we have built.

Receptors

Receptor genes were defined based on the union of the annotations from

the set of Gene Ontology (GO) terms (6,7):

GO:0043235 - receptor complex,

GO:0008305 - integrin complex,

GO:0072657 - protein localized to membrane

GO:0043113 - receptor clustering

GO:0004872 - receptor activity,

GO:0009897 - external side of plasma membrane)

UniProt annotations

search term -"Receptor [KW-0675]" go:0005886 organism:human.

This created a set of 4364 receptor genes (prior to manual curation)

Ligands

Ligand genes were defined based on the union of the below annotations

the GO terms (6,7):

GO:0005102 - receptor binding

the set of proteins labelled as secreted in the Secretome dataset (http://www.proteinatlas.org/humanproteome/secretome) (8).

This created a set of 3209 Ligand genes (prior to manual curation)

Extracellular Matrix

Extracellular Matrix (ECM) genes were defined based on the union of the annotations from

the GO terms (6,7):

GO:0031012 - extracellular matrix

GO:0005578 - proteinacious extracellular matrix

GO:0005201 - extracellular matrix structural constituent

GO:1990430 - extracellular matrix protein binding

GO:0035426 - extracellular matrix cell signalling

This created a set of 433 ECM genes (prior to manual curation)

Manual Curation

ECM, Receptor and ligand lists were manually curated

genes that were neither receptors or ligands were removed

misclassified genes were moved to the correct list (i.e. receptors found on the ligand list or vice versa)

After curation, the resulting ligand, receptor and ECM sets consisted of:

Receptors - 1851 genes

Ligands - 1593 genes

ECM - 433 genes

In each of the above sets there are genes that are part of other sets (e.g. a gene can be ECM and ligand at the same time)

Interaction Data

The set of protein interactions were downloaded from:

iRefIndex (version 14) (9). - all BioGRID interactions were excluded from the iRefIndex set as we imported the original source.

Pathway Commons (version 8) (10).

BioGRID (version 3.4.147) (11).

The entire interaction set was filtered to only include interactions that contained receptor-ligand, receptor-receptor, ligand-ligand, receptor-ecm, ligand-ecm or ecm-ecm interactions where the receptor, ligands and ecm were defined by the above lists.

The resulting Receptor-Ligand network contained 2,593 unique proteins and 38,446 unique interactions (115,900 interaction total)

Data files

ligands.txt - table of ligands. (contains HGNC symbol and classification (Ligand, Ligand/ECM, Ligand/Receptor, Ligand/ECM/Receptor)

receptors.txt - table of receptors. (contains HGNC symbol and classification (Receptor, Receptor/ECM, Ligand/Receptor, Ligand/ECM/Receptor)

ecm.txt - table of ECM. (contains HGNC symbol and classification (ECM, ECM/Receptor, ECM/Ligand, Ligand/ECM/Receptor)

protein_types.txt - table of unique set of receptor, ligand and ECM genes (all of the above tables: contains HGNC symbol as well as classification (Receptor, Ligand, ECM, ECM/Receptor, ECM/Ligand, Receptor/Ligand, Ligand/ECM/Receptor)

receptor_ligand_interactions_mitab_v1.0_April2017.txt(.zip/.gz) - tab delimited file in mitab 2.5 format containing the following columns:

AliasA - main Alias for molecule A (often the recognized gene symbol)

AliasB- main Alias for molecule B (often the recognized gene symbol)

uidA - unique identifier for molecule A (depending on the source database this can be one of the following types uniprot, refseq, entrez gene id, ensembl)

uidB - unique identifier for molecule A (depending on the source database this can be one of the following types uniprot, refseq, entrez gene id, ensembl)

altA - list of alternate identifiers for molecule A.

altB - list of alternate identifiers for molecule B.

aliasA - list of alternate aliases for molecule A.

aliasB - list of alternate aliases for molecule B.

method - list of psi-mi terms indicating experimental methods used to discover interaction.

author - text listing authors

pmids - list of pmids associated with the interaction.

taxa - taxon id for molecule A.

taxb - taxon id for molecule B.

interactionType - list of psi-mi terms indicating the type of interactions it is.

sourcedb - source database.

interactionIdentifier - source database interaction identifier

confidence - confidence of interaction as supplied by database source

References

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Razick S, Magklaras G, Donaldson IM. iRefIndex: a consolidated protein interaction database with provenance. BMC Bioinformatics. 2008 Sep 30;9:405
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Cerami EG, Gross BE, Demir E, Rodchenkov I, Babur O, Anwar N, Schultz N, Bader GD, Sander C. Pathway Commons, a web resource for biological pathway data. Nucleic Acids Res. 2011 Jan;39(Database issue):D685-90.2010 Nov 10.
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Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M. BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9.
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