Assembling the interactome of human extracellular matrix to understand its role in health and disease

Graham Cromar and John Parkinson

Department of Molecular and Medical Genetics, University of TorontoProgram in Molecular Structure and Function, Hospital for Sick Children, Toronto

Goh et al. 2007. PNAS The human disease network.

Biological Networks

Aims

Gain insight into how the ECM network evolved

How is the Extracellular Matrix organized?•List of components?•How are they organized?•What are the important functional units?

Understand elastin within the context of surrounding matrix•What does it interact with?•How central is elastin to this network?

•Did important functional units always exit?•Did some proteins arise in association with specific adaptations?•What did the network look like when elastin emerged?

Approach

Ensembl

Database of ECM proteins

Search

Cellular Component = ECMBiological ProcessMolecular Function

Gene Ontology

RefSeqUniprot

Protein Databases

Filter

IntAct

Mint

DIP

BioGRID

Interaction Databases

Results

• Initial map consisting of 361 nodes (547 edges).

• A considerable number (40%) of ECM proteins appear to have no known interactions.

• Many human ECM proteins are incompletely annotated in GO.

• Rat proteins are well-annotated in comparison to their human orthologues.

NID2 FBN2 FBN1 FBLN2 FBLN1 LOX BGN DCN

MAFP FCN1 PRTN3 FKBP10 LYZ SPINK1

ELA2 ASS GALS3

ELN

Future Work• Expand the number of GO terms used

• Use annotations from Rat/Mouse orthologues to extend human network.

• Look at other interaction databases to complement this data.

Supported by:

Restracomp