CHARACTERISATION OF ESSENTIAL PROTEINS IN PROTEINS INTERACTION NETWORKS (Pencirian Protein-protein Utama dalam Rangkaian Interaksi Protein)

The identification of essential proteins is theoretically and practically important as it is essential to understand the minimal surviving requirements for cellular lives, and it is fundamental of drug development. As conducting experimental studies to identify essential proteins are both time and resource consuming, here we present a computational approach in predicting them based on network topology properties from protein-protein interaction networks of Saccharomyces cerevisiae, Escherichia coli and Drosophila melanogaster. The proposed method, namely EP 3 NN (Essential Proteins Prediction using Probabilistic Neural Network), employed a machine learning algorithm called Probabilistic Neural Network as a classifier to identify essential proteins of the organism of interest. EP 3 NN uses degree centrality, closeness centrality, local assortativity and local clustering coefficient of each protein in the network for such predictions. Results show that EP 3 NN managed to successfully predict essential proteins with an average accuracy of 95% for our studied organisms. Results also show that most of the essential proteins are close to other proteins, have assortativity behaviour and form clusters/ sub-graph in the network.

[1]  Vol XXVmI,et al.  Public Health Reports , 1941, The Indian medical gazette.

[2]  D. F. Specht,et al.  Probabilistic neural networks for classification, mapping, or associative memory , 1988, IEEE 1988 International Conference on Neural Networks.

[3]  Donald F. Specht,et al.  Probabilistic neural networks and the polynomial Adaline as complementary techniques for classification , 1990, IEEE Trans. Neural Networks.

[4]  Timothy Masters,et al.  Advanced algorithms for neural networks: a C++ sourcebook , 1995 .

[5]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[6]  Alan F. Murray,et al.  IEEE International Conference on Neural Networks , 1997 .

[7]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[8]  P. Lasko The Drosophila melanogaster Genome: Translation Factors and RNA Binding Proteins , 2000 .

[9]  Ioannis Xenarios,et al.  DIP: the Database of Interacting Proteins , 2000, Nucleic Acids Res..

[10]  A. Servin,et al.  Escherichia coli strains colonising the gastrointestinal tract protect germfree mice againstSalmonella typhimuriuminfection , 2001, Gut.

[11]  David J. Galas,et al.  A duplication growth model of gene expression networks , 2002, Bioinform..

[12]  S. Cole Comparative mycobacterial genomics as a tool for drug target and antigen discovery , 2002, European Respiratory Journal.

[13]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[14]  A. Wagner How the global structure of protein interaction networks evolves , 2002, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[15]  J. W. Campbell,et al.  Experimental Determination and System Level Analysis of Essential Genes in Escherichia coli MG1655 , 2003, Journal of bacteriology.

[16]  G. Rubin,et al.  The Drosophila melanogaster genome. , 2003, Annual review of genomics and human genetics.

[17]  H. Bussey,et al.  Large‐scale essential gene identification in Candida albicans and applications to antifungal drug discovery , 2003, Molecular microbiology.

[18]  B. Yegnanarayana,et al.  Artificial Neural Networks , 2004 .

[19]  Ren Zhang,et al.  DEG: a database of essential genes. , 2004, Nucleic acids research.

[20]  Ka-Lok Ng,et al.  A cross-species study of the protein-protein interaction networks via the random graph approach , 2004, Proceedings. Fourth IEEE Symposium on Bioinformatics and Bioengineering.

[21]  R. Vogt,et al.  Escherichia Coli O157:H7 Outbreak Associated with Consumption of Ground Beef, June–July 2002 , 2005, Public health reports.

[22]  Alessandro Flammini,et al.  Characterization and modeling of protein–protein interaction networks , 2005 .

[23]  S. Coulomb,et al.  Gene essentiality and the topology of protein interaction networks , 2005, Proceedings of the Royal Society B: Biological Sciences.

[24]  G. Arndt,et al.  Genome‐wide screening for gene function using RNAi in mammalian cells , 2005, Immunology and cell biology.

[25]  Chien-Hung Huang,et al.  Study of the protein-protein interaction networks via random graph approach , 2005, Fourth IEEE Conference on Cognitive Informatics, 2005. (ICCI 2005)..

[26]  Michael R. Seringhaus,et al.  Predicting essential genes in fungal genomes. , 2006, Genome research.

[27]  Javid Taheri,et al.  Artificial Neural Networks , 2006, Handbook of Nature-Inspired and Innovative Computing.

[28]  Albert Y. Zomaya Handbook of Nature-Inspired and Innovative Computing - Integrating Classical Models with Emerging Technologies , 2006 .

[29]  Ernesto Estrada Virtual identification of essential proteins within the protein interaction network of yeast , 2005, Proteomics.

[30]  Stephen C. J. Parker,et al.  Towards the identification of essential genes using targeted genome sequencing and comparative analysis , 2006, BMC Genomics.

[31]  Max E. Valentinuzzi Handbook of bioinspired algorithms and applications , 2006, BioMedical Engineering OnLine.

[32]  Renata Vieira,et al.  In silico network topology-based prediction of gene essentiality , 2007, 0709.4206.

[33]  Falk Schreiber,et al.  Analysis of Biological Networks , 2008 .

[34]  Ney Lemke,et al.  Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information , 2009, BMC Bioinformatics.

[35]  V. Sheeba The Drosophila melanogaster circadian pacemaker circuit , 2008, Journal of Genetics.

[36]  S. Lovell,et al.  Protein-protein interaction networks and biology—what's the connection? , 2008, Nature Biotechnology.

[37]  Albert Y. Zomaya,et al.  Local assortativity and growth of Internet , 2009 .

[38]  Albert Y. Zomaya,et al.  Assortative mixing in directed biological networks , 2012, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[39]  Klaus Lehnertz,et al.  Assortative mixing in functional brain networks during epileptic seizures , 2013, Chaos.