Type

Journal Article

Authors

Gerard Cagney
Denis C. Shields
Nevan Krogan
Fergal Casey

Subjects

Biochemistry

Topics
molecular sequence annotation metabolism epistasis genetic multiprotein complexes models biological protein interaction domains and motifs physiology protein interaction maps yeasts

Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs. (2011)

Abstract Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Gerard Cagney, Denis C. Shields, Nevan Krogan, Fergal Casey

Experts in our system

1
Gerard Cagney
Royal College of Surgeons in Ireland
Total Publications: 54
 
2
Denis C. Shields
University College Dublin
Total Publications: 123
 
3
Nevan J. Krogan
University College Dublin
Total Publications: 15