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Function Prediction of Protein Complexes Function Prediction of Protein Complexes with Domain Correlationwith Domain Correlation
Ya Zhang Xue-Wen Chen
University of Kansas
IntroductionIntroductionProtein 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
MotivationMotivationPrevious 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.
Discover domain functional modulesDiscover 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.
Understanding the composition and function of protein complexes is an important research focus in biological science.
Domain cytoplasmic mitochondrial
Ribosomal_L5 YGR085c; YPR102c YDR237w Ribosomal_L23 YOL127w YDR405wRibosomal_L11 YDR418w; YEL054c YNL185cRibosomal_L2 YFR031c-a;
YIL018wYEL050c
Ribosomal_L6 YGL147c; YNL067w YHR147c
The cytoplasmic ribosomal large subunit vs. the mitochondrial ribosomal large subunit:
Both function for protein synthesisShare no single protein but 14 domains
MethodMethodDomain functional modules
Set of domains that perform some elementary functions in protein complexes.Extensively shared among protein complexes.
Domain-domain networkNodes: domainsEdges: shared membership
High-throughput Protein ComplexesHigh-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.
ComplexID
Function(Pred.)
MIPS annotation
550.1.108 Protein synthesis
probably protein synthesis turnover
550.1.104 Protein synthesis
probably protein synthesis turnover
550.1.140; 550.1.142;550.1.155
DNA replication probably RNA metabolism
550.1.39; 550.1.42
oxidoreductase probably intermediate and energy metabolism
550.2.56 DNA replication N/A550.1.190550.1.211; 550.1.220; 550.1.205;550.1.228
DNA replication probably transcription/DNA maintanance/chromatin structure
Domain Functional Modules Protein Complexes
RNA_pol_Rpb1_1; RNA_pol_Rpb1_2; RNA_pol_Rpb1_3; RNA_pol_Rpb1_4; RNA_pol_Rpb1_5; RNA_pol_L; RNA_pol_A_bac; RNA_pol_Rpb2_1; RNA_pol_Rpb2_2; RNA_pol_Rpb2_3; RNA_pol_Rpb2_5; RNA_pol_Rpb2_6; RNA_pol_Rpb2_7; RNA_pol_Rpb5_N; RNA_pol_Rpb5_C; DNA_RNApol_7kD; RNA_pol_N; RNA_pol_Rpb8; RNA_pol_Rpb6
RNA polymerase I; RNA polymerase II; RNA polymerase III
Ribosomal_L14; Ribosomal_L1; Ribosomal_L5; Ribosomal_L5_C; Ribosomal_L23; Ribosomal_L6; KOW; Ribosomal_L11_N; Ribosomal_L11; Ribosomal_L2; Ribosomal_L2_C; L15; Ribosomal_L3; Ribosomal_L13
cytoplasmic ribosomal large subunit; mitochondrial ribosomal large subunit
Ribosomal_S17; Ribosomal_S9; S4; Ribosomal_S5; Ribosomal_S5_C; Ribosomal_S14; Ribosomal_S10; Ribosomal_S15; Ribosomal_S2; Ribosomal_S7; Ribosomal_S19
mitochondrial ribosomal small subunit; cytoplasmic ribosomal small subunit
Transket_pyr; Pyr_redox_2; Pyr_redox; Biotin_lipoyl; 2-oxoacid_dh; E1_dh; GIDA; Pyr_redox_dim
Pyruvate dehydrogenase; 2-oxoglutarate dehydrogenas
Results: hypercliquesResults: hypercliques
Results: function predictionResults: function prediction
Discover domain functional modulesDiscover domain functional modules Discover domain functional modules as
cliques in domain-domain network
Protein Complexes(Higher order
functions)Domain Functional
Modules(Elementary functions)
C1 C2
C3
M1 M2
Two criteria Frequency of
occurrence Correlation /
association
The modules indicate the functions of the corresponding protein complexes.
Identify domain functional modules as hyperclique patterns (Xiong et al. 2005).