Finding cliques in protein interaction networks via transitive closure of a weighted graph

Finding protein functional modules in protein interaction networks amounts to finding densely connected subgraphs. Standard methods such as cliques and k-cores produce very small subgraphs due to highly sparse connections in most protein networks. Furthermore, standard methods are not applicable on weighted protein networks. We propose a method to identify cliques on weighted graphs. To overcome the sparsity problem, we introduce the concept of transitive closure on weighted graphs which is based on enforcing a transitive affinity inequality on the connection weights, and an algorithm to compute them. Using protein network from TAP-MS experiment on yeast, we discover a large number of cliques that are densely connected protein modules, with clear biological meanings as shown on Gene Ontology analysis.

[1]  P. Legrain,et al.  A genomic approach of the hepatitis C virus generates a protein interaction map. , 2000, Gene.

[2]  Gary D Bader,et al.  Analyzing yeast protein–protein interaction data obtained from different sources , 2002, Nature Biotechnology.

[3]  B. Snel,et al.  Comparative assessment of large-scale data sets of protein–protein interactions , 2002, Nature.

[4]  L. Mirny,et al.  Protein complexes and functional modules in molecular networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Herzel,et al.  Is there a bias in proteome research? , 2001, Genome research.

[6]  Ting Chen,et al.  Assessment of the reliability of protein-protein interactions and protein function prediction , 2002, Pacific Symposium on Biocomputing.

[7]  B. Schwikowski,et al.  A network of protein–protein interactions in yeast , 2000, Nature Biotechnology.

[8]  Jong H. Park,et al.  Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast. , 2001, Journal of molecular biology.

[9]  D. Eisenberg,et al.  Detecting protein function and protein-protein interactions from genome sequences. , 1999, Science.

[10]  P. Bork,et al.  Functional organization of the yeast proteome by systematic analysis of protein complexes , 2002, Nature.

[11]  T. Ito,et al.  Toward a protein-protein interaction map of the budding yeast: A comprehensive system to examine two-hybrid interactions in all possible combinations between the yeast proteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Kaleem Siddiqi,et al.  Matching Hierarchical Structures Using Association Graphs , 1999, IEEE Trans. Pattern Anal. Mach. Intell..

[14]  R. Tibshirani.  Regression Shrinkage and Selection via the Lasso , 1996 .

[15]  Anton J. Enright,et al.  Protein interaction maps for complete genomes based on gene fusion events , 1999, Nature.

[16]  Hui Xiong,et al.  Identification of Functional Modules in Protein Complexes via Hyperclique Pattern Discovery , 2004, Pacific Symposium on Biocomputing.

[17]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[18]  David A. Gough,et al.  Predicting protein-protein interactions from primary structure , 2001, Bioinform..

[19]  Florian Iragne,et al.  IPPRED: Server for Proteins Interactions Inference , 2003, Bioinform..

[20]  J. Wojcik,et al.  The protein–protein interaction map of Helicobacter pylori , 2001, Nature.

[21]  Xiaofeng He,et al.  A unified representation of multiprotein complex data for modeling interaction networks , 2004, Proteins.

[22]  Roded Sharan,et al.  Identification of protein complexes by comparative analysis of yeast and bacterial protein interaction data , 2004, J. Comput. Biol..

[23]  S. Fields,et al.  Genome-wide analysis of vaccinia virus protein-protein interactions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[25]  T. Motzkin,et al.  Maxima for Graphs and a New Proof of a Theorem of Turán , 1965, Canadian Journal of Mathematics.