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The topological characteristics of biological networks enable us to identify the key nodes in terms of modularity. However, due to a large size of the biological networks with many hubs and functional modules across intertwined layers within the network, it often becomes difficult to accomplish the task of identifying potential key regulators. We use for the first time a generalized formalism of Hamiltonian Energy (HE) with a recursive approach. The concept, when applied to the Apoptosis Regulatory Gene Network (ARGN), helped us identify 11 Motif hubs (MHs), which influenced the network up to motif levels. The approach adopted allowed to classify MHs into 5 significant motif hubs (S-MHs) and 6 non-significant motif hubs (NS-MHs). The significant motif hubs had a higher HE value and were considered as high-active key regulators; while the non-significant motif hubs had a relatively lower HE value and were considered as low-active key regulators, in network control mechanism. Further, we compared the results of the HE analyses with the topological characterization, after subjecting to the three conditions independently: (i) removing all MHs, (ii) removing only S-MHs, and (iii) removing only NS-MHs from the ARGN. This procedure allowed us to cross-validate the role of 5 S-MHs, NFk-B1, BRCA1, CEBPB, AR, and POU2F1 as the potential key regulators. The changes in HE calculations further showed that the removal of 5 S-MHs could cause perturbation at all levels of the network, a feature not discernible by topological analysis alone. [ABSTRACT FROM AUTHOR]

The breast cancer network constructed from 70 experimentally verified genes is found to follow hierarchical scale free nature with heterogeneous modular organization and diverge leading hubs. The topological parameters (degree distributions, clustering co-efficient, connectivity and centralities) of this network obey fractal rules indicating absence of centrality lethality rule, and efficient communication among the components. From the network theoretical approach, we identified few key regulators out of large number of leading hubs, which are deeply rooted from top to down of the network, serve as backbone of the network, and possible target genes. However, p53, which is one of these key regulators, is found to be in low rank and keep itself at low profile but directly cross-talks with important genes BRCA2 and BRCA3. The popularity of these hubs gets changed in unpredictable way at various levels of organization thus showing disassortive nature. The local community paradigm approach in this network shows strong correlation of nodes in majority of modules/sub-modules (fast communication among nodes) and weak correlation of nodes only in few modules/sub-modules (slow communication among nodes) at various levels of network organization. [ABSTRACT FROM AUTHOR]

Background: India is endemic to Japanese encephalitis virus (JEV) and recurrent outbreaks occur mainly in rice growing areas. Pigs are considered to be the amplifying host for JEV and infection in gestating pigs results in reproductive failure. Most studies conducted on JEV infection in Indian pigs have been serological surveys and very little is known about JEV genotypes circulating in pigs. So the potential risk posed by pigs in JEV transmission and the genetic relationship between viruses circulating in pigs, mosquitoes and humans is poorly understood. Methodology/Principal Findings: This study was conducted in pigs with a history of reproductive failure characterized by stillborn piglets with neuropathological lesions. Japanese encephalitis (JE) suspected brain specimens inoculated intracerebrally into mice and Vero cells resulted in successful isolation of JEV/SW/IVRI/395A/2014. Clinicopathological observations in infected mice, demonstration of JEV antigen in brain, and analysis of the envelope protein identified the swine isolate as being neurovirulent. Phylogenetic analysis based on prM and E gene sequences showed that it belonged to genotype III. This swine isolate was closely related to JEV associated with the 2005 outbreak in India and JaoArS982 from Japan. Phylogenetic analysis of JEV strains collected between 1956 and 2014 in India categorized the GIII viruses into different clades blurring their spatial distribution, which has been discernible in the previous century. Conclusions/Significance: Isolation of JEV from stillborn piglets and its close genetic relationship with viruses detected at least three decades ago in humans and mosquitoes in Japan suggests that the virus may have been circulating among Indian pigs for several decades. The close similarity between the present swine isolate and those detected in humans affected in the 2005 outbreak in Uttar Pradesh, India, suggests the need for more intensive surveillance of pigs and implementation of suitable strategies to control JE in India. [ABSTRACT FROM AUTHOR]