In silico construction of a protein interaction landscape for nucleotide excision repair

To obtain a systems-level perspective on the topological and functional relationships among proteins contributing to nucleotide excision repair (NER) in Saccharomyces cerevisiae, we built two models to analyze protein-protein physical interactions. A recursive computational model based on set theory systematically computed overlaps among protein interaction neighborhoods. A statistical model scored computation results to detect significant overlaps which exposed protein modules and hubs concurrently. We used these protein entities to guide the construction of a multi-resolution landscape which showed relationships among NER, transcription, DNA replication, chromatin remodeling, and cell cycle regulation. Literature curation was used to support the biological significance of identified modules and hubs. The NER landscape revealed a hierarchical topology and a recurrent pattern of kernel modules coupling a variety of proteins in structures that provide diverse functions. Our analysis offers a computational framework that can be applied to construct landscapes for other biological processes.