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Current methods for the detection of differential gene expression focus on finding individual genes that may be responsible for certain diseases or external irritants. However, for common genetic diseases, multiple genes and their interactions should be understood and treated together during the exploration of disease causes and possible drug design. The present study focuses on analyzing the dynamic patterns of co-regulated modules during biological progression and determining those having remarkably varying activities, using the yeast cell cycle as a case study. We first constructed dynamic active protein-protein interaction networks by modeling the activity of proteins and assembling the dynamic co-regulation protein network at each time point. The dynamic active modules were detected using a method based on the Bayesian graphical model and then the modules with the most varied dispersion of clustering coefficients, which could be responsible for the dynamic mechanism of the cell cycle, were identified. Comparison of results from our functional module detection with the state-of-art functional module detection methods and validation of the ranking of activities of functional modules using GO annotations demonstrate the efficacy of our method for narrowing the scope of possible essential responding modules that could provide multiple targets for biologists to further experimentally validate.


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Co-regulated Protein Functional Modules with Varying Activities in Dynamic PPI Networks

Show Author's information Yuan ZhangNan DuKang LiKebin Jia( )Aidong Zhang
Department of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124, China
Department of Computer Science and Engineering, State University of New York at Buffalo, Buffalo, NY 14260-2500, USA

Abstract

Current methods for the detection of differential gene expression focus on finding individual genes that may be responsible for certain diseases or external irritants. However, for common genetic diseases, multiple genes and their interactions should be understood and treated together during the exploration of disease causes and possible drug design. The present study focuses on analyzing the dynamic patterns of co-regulated modules during biological progression and determining those having remarkably varying activities, using the yeast cell cycle as a case study. We first constructed dynamic active protein-protein interaction networks by modeling the activity of proteins and assembling the dynamic co-regulation protein network at each time point. The dynamic active modules were detected using a method based on the Bayesian graphical model and then the modules with the most varied dispersion of clustering coefficients, which could be responsible for the dynamic mechanism of the cell cycle, were identified. Comparison of results from our functional module detection with the state-of-art functional module detection methods and validation of the ranking of activities of functional modules using GO annotations demonstrate the efficacy of our method for narrowing the scope of possible essential responding modules that could provide multiple targets for biologists to further experimentally validate.

Keywords: dynamic protein-protein interaction networks, dynamic active modules, varying activities, Bayesian graphical mode

References(23)

[1]
X.Chang, T.Xu, Y.Li, and K.Wang, Dynamic modular architecture of protein-protein interaction networks beyond the dichotomy of/date/’and/party/’hubs, Scientific Reports, vol. 3, article no. 1691, 2013.
[2]
K.Komurovand M.White, Revealing static and dynamic modular architecture of the eukaryotic protein interaction network, Molecular Systems Biology, vol. 3, no. 1, article no. 110, 2007.
[3]
U. deLichtenberg, L. J.Jensen, S.Brunak, and P.Bork, Dynamic complex formation during the yeast cell cycle, Science, vol. 307, no. 5710, pp. 724-727, 2005.
[4]
V. G.Tusher, R.Tibshirani, and G.Chu, Significance analysis of microarrays applied to the ionizing radiation response, Proceedings of the National Academy of Sciences, vol. 98, no. 9, pp. 5116-5121, 2001.
[5]
W.Pan, A comparative review of statistical methods for discovering differentially expressed genes in replicated microarray experiments, Bioinformatics, vol. 18, no. 4, pp. 546-554, 2002.
[6]
N.Du, Y.Zhang, K.Li, J.Gao, S. D.Mahajan, B. B.Nair, S. A.Schwartz, and A.Zhang, Evolutionary analysis of functional modules in dynamic ppi networks, in Proceedings of the ACM Conference on Bioinformatics, Computational Biology and Biomedicine, ACM, 2012, pp. 250-257.
[7]
J.-D.Han, N.Bertin, T.Hao, D. S.Goldberg, G. F.Berriz, L. V.Zhang, D.Dupuy, A. J.Walhout, M. E.Cusick, F. P.Roth, and M.Vidal, Evidence for dynamically organized modularity in the yeast protein-protein interaction network, Nature, vol. 430, no. 6995, pp. 88-93, 2004.
[8]
I. W.Taylor, R.Linding, D.Warde-Farley, Y.Liu, C.Pesquita, D.Faria, S.Bull, T.Pawson, Q.Morris, and J. L.Wrana, Dynamic modularity in protein interaction networks predicts breast cancer outcome, Nature Biotechnology, vol. 27, no. 2, pp. 199-204, 2009.
[9]
K.Tarassov, V.Messier, C. R.Landry, S.Radinovic, M. M. S.Molina, I.Shames, Y.Malitskaya, J.Vogel, H.Bussey, and S. W.Michnick, An in vivo map of the yeast protein interactome, Science, vol. 320, no. 5882, pp. 1465-1470, 2008.
[10]
X.Tang, J.Wang, B.Liu, M.Li, G.Chen, and Y.Pan, A comparison of the functional modules identified from time course and static ppi network data, BMC Bioinformatics, vol. 12, no. 1, p. 339, 2011.
[11]
J.Wang, X.Peng, M.Li, and Y.Pan, Construction and application of dynamic protein interaction network based on time course gene expression data, Proteomics, vol. 13, no. 2, pp. 301-312, 2013.
[12]
H. K.Lee, A. K.Hsu, J.Sajdak, J.Qin, and P.Pavlidis, Coexpression analysis of human genes across many microarray data sets, Genome Research, vol. 14, no. 6, pp. 1085-1094, 2004.
[13]
K.Basso, A. A.Margolin, G.Stolovitzky, U.Klein, R.Dalla-Favera, and A.Califano, Reverse engineering of regulatory networks in human b cells, Nature Genetics, vol. 37, no. 4, pp. 382-390, 2005.
[14]
N.Bhardwajand H.Lu, Correlation between gene expression profiles and protein-protein interactions within and across genomes, Bioinformatics, vol. 21, no. 11, pp. 2730-2738, 2005.
[15]
H.Kimand H.Park, Nonnegative matrix factorization based on alternating nonnegativity constrained least squares and active set method, SIAM Journal on Matrix Analysis and Applications, vol. 30, no. 2, pp. 713-730, 2008.
[16]
I.Psorakis, S.Roberts, M.Ebden, and B.Sheldon, Overlapping community detection using bayesian non-negative matrix factorization, Physical Review E, vol. 83, no. 6, p. 066114, 2011.
[17]
V. Y.Tanand C.Févotte, Automatic relevance determination in nonnegative matrix factorization with the β-divergence, arXiv preprint arXiv:1111.6085, 2011.
[18]
B. P.Tu, A.Kudlicki, M.Rowicka, and S. L.McKnight, Logic of the yeast metabolic cycle: Temporal compartmentalization of cellular processes, Science, vol. 310, no. 5751, pp. 1152-1158, 2005.
[19]
S.Pu, J.Wong, B.Turner, E.Cho, and S. J.Wodak, Up-to-date catalogues of yeast protein complexes, Nucleic Acids Research, vol. 37, no. 3, pp. 825-831, 2009.
[20]
F.Markowetzand O. G.Troyanskaya, Computational identification of cellular networks and pathways, Mol. Biosyst., vol. 3, no. 7, pp. 478-482, 2007.
[21]
Y.-R.Cho, L.Shi, and A.Zhang, Flownet: Flow-based approach for efficient analysis of complex biological networks, in Data Mining, 2009. ICDM’09. Ninth IEEE International Conference on, IEEE, pp. 91-100, 2009.
DOI
[22]
N. J.Krogan, G.Cagney, H.Yu, G.Zhong, X.Guo, A.Ignatchenko, J.Li, S.Pu, N.Datta, A. P.Tikuisis, et al., Global landscape of protein complexes in the yeast saccharomyces cerevisiae, Nature, vol. 440, no. 7084, pp. 637-643, 2006.
[23]
U. VonLuxburg, A tutorial on spectral clustering, Statistics and Computing, vol. 17, no. 4, pp. 395-416, 2007.
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Publication history

Received: 06 August 2013
Accepted: 07 August 2013
Published: 03 October 2013
Issue date: October 2013

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© The author(s) 2013

Acknowledgements

The research work was supported by the National Natural Science Foundation of China (No. 30970780) and Ph.D. Programs Foundation of Ministry of Education of China (No. 20091103110005).

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