Assortativity of aging key players in the dynamical networks

Human aging is the main social and medicinal challenge where it is one of the factors lead to disease. Understanding the process will be advantageous in the drugs and medicinal fields. In this study, we analyze the process through dynamic protein-protein interaction (PPI) networks by observing the topological changes of the network across ages. The dynamic networks consist of 14 ages, they are within 80 – 99 years, where we call aging-related protein networks. In each of the network, we analyzed the property of assortativity as proposed by recent study. Assortativity in PPI network is a measure to quantify the tendency of proteins to communicate with other similar proteins in the network. However, recent study proposes local assortativity for individual nodes in the network. Consequently, we are able to analyze the characteristics of aging network; i) Aging-related protein networks are disassortative with positive non-linear local assortativity, ii) there are strong and weak assortative key-players, iii) assortative key players are not close to all proteins in aging network, and iv) assortative hubs decrease the robustness of the networks.

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

[2]  Piraveenan Mahendra,et al.  Node Assortativity in Complex Networks: An Alternative Approach , 2014, ICCS.

[3]  James Nazroo,et al.  Physical activity in older age: perspectives for healthy ageing and frailty , 2016, Biogerontology.

[4]  Paolo G. V. Martini,et al.  PANP - a New Method of Gene Detection on Oligonucleotide Expression Arrays , 2007, 2007 IEEE 7th International Symposium on BioInformatics and BioEngineering.

[5]  Tijana Milenkovic,et al.  Dynamic networks reveal key players in aging , 2014, BCB.

[6]  Gesine Reinert,et al.  The Importance of Age and High Degree, in Protein-Protein Interaction Networks , 2012, J. Comput. Biol..

[7]  Albert Y. Zomaya,et al.  Classifying Complex Networks using Unbiased Local Assortativity , 2010, ALIFE.

[8]  Jhih-Rong Lin,et al.  Systems-level analysis of human aging genes shed new light on mechanisms of aging. , 2016, Human molecular genetics.

[9]  Siti Raihan Halilan,et al.  Characteristics of aging related proteins in old age , 2019, THE 2018 UKM FST POSTGRADUATE COLLOQUIUM: Proceedings of the Universiti Kebangsaan Malaysia, Faculty of Science and Technology 2018 Postgraduate Colloquium.

[10]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[11]  Adam J. Smith,et al.  The Database of Interacting Proteins: 2004 update , 2004, Nucleic Acids Res..

[12]  Amy E. Morgan,et al.  Modelling the molecular mechanisms of aging , 2017, Bioscience reports.

[13]  Tesshi Yamada,et al.  β-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells. , 2012, Gastroenterology.

[14]  M E J Newman.  Assortative mixing in networks. , 2002, Physical review letters.

[15]  I. Kohane,et al.  Gene regulation and DNA damage in the ageing human brain , 2004, Nature.

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

[17]  C. Kenyon.  The genetics of ageing , 2010, Nature.

[18]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[19]  Ashish Rajput,et al.  Systematic analysis of the gerontome reveals links between aging and age-related diseases , 2016, Human molecular genetics.

[20]  Carl W. Cotman,et al.  Gene expression changes in the course of normal brain aging are sexually dimorphic , 2008, Proceedings of the National Academy of Sciences.

[21]  Albert Y. Zomaya,et al.  Local assortativeness in scale-free networks , 2008 .

[22]  Albert Y. Zomaya,et al.  CHARACTERISATION OF ESSENTIAL PROTEINS IN PROTEINS INTERACTION NETWORKS (Pencirian Protein-protein Utama dalam Rangkaian Interaksi Protein) , 2013 .

[23]  Zilong Qiu,et al.  A Calcium-Dependent Switch in a CREST-BRG1 Complex Regulates Activity-Dependent Gene Expression , 2008, Neuron.

[24]  Marco Punta,et al.  PROTEIN INTERACTIONS AND DISEASE , 2007 .

[25]  J. Han,et al.  A modular network model of aging , 2007, Molecular systems biology.

[26]  Dean P. Jones,et al.  A network perspective on metabolism and aging. , 2010, Integrative and comparative biology.