Abstract Motivation: The building blocks of biological networks are individual protein–protein interactions (PPIs). The cumulative PPI data set in Saccharomyces cerevisiae now exceeds 78 000. Studying the network of these interactions will provide valuable insight into the inner workings of cells. Results: We performed a systematic graph theory-based analysis of this PPI network to construct computational models for describing and predicting the properties of lethal mutations and proteins participating in genetic interactions, functional groups, protein complexes and signaling pathways. Our analysis suggests that lethal mutations are not only highly connected within the network, but they also satisfy an additional property: their removal causes a disruption in network structure. We also provide evidence for the existence of alternate paths that bypass viable proteins in PPI networks, while such paths do not exist for lethal mutations. In addition, we show that distinct functional classes of proteins have differing network properties. We also demonstrate a way to extract and iteratively predict protein complexes and signaling pathways. We evaluate the power of predictions by comparing them with a random model, and assess accuracy of predictions by analyzing their overlap with MIPS database. Conclusions: Our models provide a means for understanding the complex wiring underlying cellular function, and enable us to predict essentiality, genetic interaction, function, protein complexes and cellular pathways. This analysis uncovers structure–function relationships observable in a large PPI network. Supplementary information: We are placing the full predicted tables on the web page: http://www.cs.utoronto.ca/~juris/data/b03/SuppDataTables.zip
Abstract Improved bioassays have significantly increased the rate of identifying new protein-protein interactions (PPIs), and the number of detected human PPIs has greatly excee...
Abstract The elucidation of the cell's large‐scale organization is a primary challenge for post‐genomic biology, and understanding the structure of protein interaction networks ...
A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integr...
Abstract Much of the complexity within cells arises from functional and regulatory interactions among proteins. The core of these interactions is increasingly known, but novel i...
Abstract Cellular life depends on a complex web of functional associations between biomolecules. Among these associations, protein–protein interactions are particularly importan...
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