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Bioinformatics Advance Access published online on October 27, 2004

Bioinformatics, doi:10.1093/bioinformatics/bti086
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received June 3, 2004
Revised September 1, 2004
Accepted October 5, 2004

Article

Statistical analysis of domains in interacting protein pairs

Tom M. W. Nye 1*, Carlo Berzuini 2, Walter R. Gilks 1, M. Madan Babu 3, and Sarah A. Teichmann 3

1 Medical Research Council Biostatistics Unit, Cambridge, UK
2 Medical Research Council Biostatistics Unit, Cambridge, UK; Dipartimento di Informatica e Sistemistica, Università di Pavia, Italy
3 Medical Research Council Laboratory of Molecular Biology, Cambridge, UK

* To whom correspondence should be addressed.
Tom M. W. Nye, E-mail: thomas.nye{at}mrc-bsu.cam.ac.uk


   Abstract

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 dataset 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 dataset.


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