Integrating protein-protein interaction networks with phenotypes reveals signs of interactions.

Nat Methods 2014 Jan 17;11(1):94-9. Epub 2013 Nov 17.

1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Howard Hughes Medical Institute, Boston, Massachusetts, USA.

A major objective of systems biology is to organize molecular interactions as networks and to characterize information flow within networks. We describe a computational framework to integrate protein-protein interaction (PPI) networks and genetic screens to predict the 'signs' of interactions (i.e., activation-inhibition relationships). We constructed a Drosophila melanogaster signed PPI network consisting of 6,125 signed PPIs connecting 3,352 proteins that can be used to identify positive and negative regulators of signaling pathways and protein complexes. We identified an unexpected role for the metabolic enzymes enolase and aldo-keto reductase as positive and negative regulators of proteolysis, respectively. Characterization of the activation-inhibition relationships between physically interacting proteins within signaling pathways will affect our understanding of many biological functions, including signal transduction and mechanisms of disease.

Download full-text PDF

Source
http://www.nature.com/articles/nmeth.2733
Publisher Site
http://dx.doi.org/10.1038/nmeth.2733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877743PMC
January 2014
11 Reads

Publication Analysis

Top Keywords

negative regulators
8
positive negative
8
activation-inhibition relationships
8
signaling pathways
8
protein-protein interaction
8
proteins identify
4
3352 proteins
4
connecting 3352
4
identify positive
4
protein complexes
4
pathways protein
4
ppis connecting
4
regulators signaling
4
complexes identified
4
6125 signed
4
constructed drosophila
4
relationships constructed
4
interactions activation-inhibition
4
'signs' interactions
4
drosophila melanogaster
4

References

(Supplied by CrossRef)

KG Guruharsha et al.
Cell 2011

AC Gavin et al.
Nature 2006

NJ Krogan et al.
Nature 2006

U Stelzl et al.
Cell 2005

JF Rual et al.
Nature 2005

A Friedman et al.
Cell 2007

B Kholodenko et al.
Sci. Signal. 2012

DR Hyduke et al.
Nat. Rev. Genet. 2010

DC Kirouac et al.
BMC Syst. Biol. 2012

A Vinayagam et al.
Sci. Signal. 2011

W Liu et al.
Mol. Cell Proteomics 2009

Similar Publications