Statistical analysis of domains in interacting protein pairs

• Published in: Bioinformatics 2005-04, Vol.21 (7), p.993-1001
• Main Authors: Nye, Tom M. W., Berzuini, Carlo, Gilks, Walter R., Babu, M. Madan, Teichmann, Sarah A.
• Format: Article
• Language: English
• Subjects: Algorithms; Binding Sites; Biological and medical sciences; Computer Simulation; Databases, Protein; Fundamental and applied biological sciences. Psychology; General aspects; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Models, Chemical; Models, Statistical; Protein Binding; Protein Interaction Mapping - methods; Protein Structure, Tertiary; Saccharomyces cerevisiae Proteins - analysis; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - classification; Saccharomyces cerevisiae Proteins - metabolism; Sequence Alignment - methods; Sequence Analysis, Protein - methods; Structure-Activity Relationship
• ISSN: 1367-4803; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/bti086

Motivation: Several methods have recently been developed to analyse large-scale sets of physical interactions between proteins in terms of physical contacts between the constituent domains, often with a view to predicting new pairwise interactions. Our aim is to combine genomic interaction data, in which domain–domain contacts are not explicitly reported, with the domain-level structure of individual proteins, in order to learn about the structure of interacting protein pairs. Our approach is driven by the need to assess the evidence for physical contacts between domains in a statistically rigorous way. Results: We develop a statistical approach that assigns p-values to pairs of domain superfamilies, measuring the strength of evidence within a set of protein interactions that domains from these superfamilies form contacts. A set of p-values is calculated for SCOP superfamily pairs, based on a pooled data set of interactions from yeast. These p-values can be used to predict which domains come into contact in an interacting protein pair. This predictive scheme is tested against protein complexes in the Protein Quaternary Structure (PQS) database, and is used to predict domain–domain contacts within 705 interacting protein pairs taken from our pooled data set. Contact: [e-mail]