Function Prediction of Protein Complexes with Domain Correlation Ya Zhang Xue-Wen Chen

1. C1 C2 C3 M1 M2 Function Prediction of Protein Complexes with Domain Correlation Ya Zhang Xue-Wen Chen University of Kansas Introduction • Protein complexes: groups of proteins that interact/associate with each other. • Many molecular machineries are protein complexes • e.g., proteasome, responsible for degradation of unwanted proteins, consists of more than 50 proteins Method • Domain functional modules • Set of domains that perform some elementary functions in protein complexes. • Extensively shared among protein complexes. Discover domain functional modules • Support of a set of domains X={d1, d2, .., dk}, is the fraction of protein complexes containing X. supp(X)=NX/N • H-confidence of X is: hconf(X)=supp(X)/maxi(supp(pi)) • A set of domains X ={d1, d2, .., dk} is a hyperclique pattern if hconf(X) ≥ hc and supp(X) ≥ s. Protein Complexes (Higher order functions) Domain Functional Modules (Elementary functions) • Understanding the composition and function of protein complexes is an important research focus in biological science. • The modules indicate the functions of the corresponding protein complexes. High-throughput Protein Complexes • High-throughput experiments have produced a large amount of protein complex data. • Gavin, et al. (Nature, 2002) • TAP : Tandem Affinity Purification • Ho, et al. (Nature, 2002) • HMS-PCI: High-throughput Mass Spectromic Protein Complex Identification • But the biological functions of the protein complexes are largely unknown. Results: hypercliques Discover domain functional modules • Discover domain functional modules as cliques in domain-domain network • Two criteria • Frequency of occurrence • Correlation / association Domain-domain network Nodes: domains Edges: shared membership • Identify domain functional modules as hyperclique patterns (Xiong et al. 2005). Motivation • Previous efforts in analyzing protein complex data were largely based on the protein constitution of the complexes. • Studying complexes at protein level does not always reveal the function linkage among complexes. • The cytoplasmic ribosomal large subunit vs. the mitochondrial ribosomal large subunit • In this study, we analyze the domain composition of protein complexes to predict the functions of protein complexes. Results: function prediction • The cytoplasmic ribosomal large subunit vs. the mitochondrial ribosomal large subunit: • Both function for protein synthesis • Share no single protein but 14 domains