In Silico Construction of a Protein Interaction Landscape for Nucleotide Excision Repair
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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.
KeywordsDNA repair Excision Network Computation
We thank Keziban Űnsal-Kaçmaz and Marila Cordeiro-Stone for helpful discussions and ideas and Dan Reed for initial support of this work. Nancy Tran was supported by the Leon and Bertha Goldberg Fellowship. Funding was also provided by PHS grants (ES014635, ES011391, ES010126, CA081343, GM070335, CA074015) and NSF grants to the National Center for Supercomputing Applications (CA SCI-0525308 and CSA SCI-0438712).
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