Integrating gene and protein expression data with genome-scale metabolic networks to infer functional pathways

This article has been made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Pey et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The study of cellular metabolism in the context of high-throughput -omics data has allowed us to decipher novel mechanisms of importance in biotechnology and health. To continue with this progress, it is essential to efficiently integrate experimental data into metabolic modeling. Results: We present here an in-silico framework to infer relevant metabolic pathways for a particular phenotype under study based on its gene/protein expression data. This framework is based on the Carbon Flux Path (CFP) approach, a mixed-integer linear program that expands classical path finding techniques by considering additional biophysical constraints. In particular, the objective function of the CFP approach is amended to account for gene/protein expression data and influence obtained paths. This approach is termed integrative Carbon Flux Path (iCFP). We show that gene/protein expression data also influences the stoichiometric balancing of CFPs, which provides a more accurate picture of active metabolic pathways. This is illustrated in both a theoretical and real scenario. Finally, we apply this approach to find novel pathways relevant in the regulation of acetate overflow metabolism in Escherichia coli. As a result, several targets which could be relevant for better understanding of the phenomenon leading to impaired acetate overflow are proposed. Conclusions: A novel mathematical framework that determines functional pathways based on gene/protein expression data is presented and validated. We show that our approach is able to provide new insights into complex biological scenarios such as acetate overflow in Escherichia coli.Basque Governmen

Tracking advanced persistent threats in critical infrastructures through opinion dynamics

Advanced persistent threats pose a serious issue for modern industrial environments, due to their targeted and complex attack vectors that are difficult to detect. This is especially severe in critical infrastructures that are accelerating the integration of IT technologies. It is then essential to further develop effective monitoring and response systems that ensure the continuity of business to face the arising set of cyber-security threats. In this paper, we study the practical applicability of a novel technique based on opinion dynamics, that permits to trace the attack throughout all its stages along the network by correlating different anomalies measured over time, thereby taking the persistence of threats and the criticality of resources into consideration. The resulting information is of essential importance to monitor the overall health of the control system and cor- respondingly deploy accurate response procedures. Advanced Persistent Threat Detection Traceability Opinion Dynamics.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Enhancing security and dependability of industrial networks with opinion dynamics

Opinion Dynamics poses a novel technique to accurately locate the patterns of an advanced attack against an industrial infrastructure, compared to traditional intrusion detection systems. This distributed solution provides pro table information to identify the most a ected areas within the network, which can be leveraged to design and deploy tailored response mechanisms that ensure the continuity of the service. In this work, we base on this multi-agent collaborative approach to propose a response technique that permits the secure delivery of messages across the network. For such goal, our contribution is twofold: rstly, we rede ne the existing algorithm to assess not only the compromise of nodes, but also the security and quality of service of communication links; secondly, we develop a routing protocol that prioritizes the secure paths throughout the topology considering the information obtained from the detection system.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Implications for conservation and game management of the roadkill levels of the endemic Iberian hare (Lepus granatensis)

The Iberian hare (Lepus granatensis) is an important small game species endemic to the Iberian Peninsula for which the incidence of roadkill is unknown. We surveyed Iberian hare–vehicle accidents on road networks in southern Spain, focusing on roads that mainly run through favorable habitats for this species: Mediterranean landscapes with plots of arable crops, olive groves, and vineyards. We recorded roadkills over a 5-month period, estimated hare accident densities on roads, and compared these numbers to hare hunting yields in adjoining hunting estates. We also analyzed the spatial patterns of and potential factors influencing hare roadkills. We detected the existence of black spots for hare roadkills in areas with high landscape heterogeneity that also included embankments and nearby crossroads and had high traffic intensity. Hare roadkill levels ranged from 5 to 25% of the annual harvest of hares killed on neighboring hunting estates. We suggest that road collisions should be considered in Iberian hare conservation in addition to hunting, since they may represent an additive source of mortality. Game managers should address the issue of hare roadkill in harvest planning to compensate for hare accidents, adjusting hunting quotas to account for this unnatural source of mortality. Our results suggest future directions for applied research in road ecology, including further work on demographic compensation and roadkill mitigation