10 research outputs found
Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks
The idea of 'date' and 'party' hubs has been influential in the study of
protein-protein interaction networks. Date hubs display low co-expression with
their partners, whilst party hubs have high co-expression. It was proposed that
party hubs are local coordinators whereas date hubs are global connectors. Here
we show that the reported importance of date hubs to network connectivity can
in fact be attributed to a tiny subset of them. Crucially, these few, extremely
central, hubs do not display particularly low expression correlation,
undermining the idea of a link between this quantity and hub function. The
date/party distinction was originally motivated by an approximately bimodal
distribution of hub co-expression; we show that this feature is not always
robust to methodological changes. Additionally, topological properties of hubs
do not in general correlate with co-expression. Thus, we suggest that a
date/party dichotomy is not meaningful and it might be more useful to conceive
of roles for protein-protein interactions rather than individual proteins. We
find significant correlations between interaction centrality and the functional
similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure
Structure of Protein Interaction Networks and Their Implications on Drug Design
Protein-protein interaction networks (PINs) are rich sources of information that enable the network properties of biological systems to be understood. A study of the topological and statistical properties of budding yeast and human PINs revealed that they are scale-rich and configured as highly optimized tolerance (HOT) networks that are similar to the router-level topology of the Internet. This is different from claims that such networks are scale-free and configured through simple preferential-attachment processes. Further analysis revealed that there are extensive interconnections among middle-degree nodes that form the backbone of the networks. Degree distributions of essential genes, synthetic lethal genes, synthetic sick genes, and human drug-target genes indicate that there are advantageous drug targets among nodes with middle- to low-degree nodes. Such network properties provide the rationale for combinatorial drugs that target less prominent nodes to increase synergetic efficacy and create fewer side effects