Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

On the tractability of the piecewise-linear approximation for general discrete-choice network revenue management

The choice network revenue management (RM) model incorporates customer purchase behavioras customers purchasing products with certain probabilities that are a function of the offeredassortment of products, and is the appropriate model for airline and hotel network revenuemanagement, dynamic sales of bundles, and dynamic assortment optimization. The underlyingstochastic dynamic program is intractable and even its certainty-equivalence approximation, inthe form of a linear program called Choice Deterministic Linear Program (CDLP) is difficultto solve in most cases. The separation problem for CDLP is NP-complete for MNL with justtwo segments when their consideration sets overlap; the affine approximation of the dynamicprogram is NP-complete for even a single-segment MNL. This is in contrast to the independentclass(perfect-segmentation) case where even the piecewise-linear approximation has been shownto be tractable. In this paper we investigate the piecewise-linear approximation for network RMunder a general discrete-choice model of demand. We show that the gap between the CDLP andthe piecewise-linear bounds is within a factor of at most 2. We then show that the piecewiselinearapproximation is polynomially-time solvable for a fixed consideration set size, bringing itinto the realm of tractability for small consideration sets; small consideration sets are a reasonablemodeling tradeoff in many practical applications. Our solution relies on showing that forany discrete-choice model the separation problem for the linear program of the piecewise-linearapproximation can be solved exactly by a Lagrangian relaxation. We give modeling extensionsand show by numerical experiments the improvements from using piecewise-linear approximationfunctions.

Construction and performance of network codes

El principal objectiu d'aquest treball és implementar i exposar una descripció teòrica per a diferents esquemes de Physical Layer Network Coding. Utilitzant un esquema bàsic com a punt de partida, el projecte presenta la construcció i l'anàlisis de diferents esquemes de comunicació on la complexitat va augmentant a mesura que anem avançant en el projecte. El treball està estructurat en diferents parts: primer, es presenta una introducció a Physical Layer Network Coding i a Lattice Network Codes. A continuació, s'introdueixen les eines matemàtiques necessàries per entendre el CF System. Després, s'analitza i implementa el primer esquema bàsic. A partir del qual, implementem una versió vectorial del CF System i una versió codificada amb un Hamming q-ari. Finalment, s'estudien i implementen diferents estratègies per millorar la matriu de coeficients A.

Transfer entropy reconstruction and labeling of neuronal connections from simulated calcium imaging

Neuronal dynamics are fundamentally constrained by the underlying structural network architecture, yet much of the details of this synaptic connectivity are still unknown even in neuronal cultures in vitro. Here we extend a previous approach based on information theory, the Generalized Transfer Entropy, to the reconstruction of connectivity of simulated neuronal networks of both excitatory and inhibitory neurons. We show that, due to the model-free nature of the developed measure, both kinds of connections can be reliably inferred if the average firing rate between synchronous burst events exceeds a small minimum frequency. Furthermore, we suggest, based on systematic simulations, that even lower spontaneous inter-burst rates could be raised to meet the requirements of our reconstruction algorithm by applying a weak spatially homogeneous stimulation to the entire network. By combining multiple recordings of the same in silico network before and after pharmacologically blocking inhibitory synaptic transmission, we show then how it becomes possible to infer with high confidence the excitatory or inhibitory nature of each individual neuron.

Innovación y Aprendizaje: un nuevo modelo para la formación universitaria: ¿Por qué y para qué? = Innovation and Learning: a New Model for University Education: Why and for What?

The legislative reforms in university matters driven in recent years, beyond the provoked controversies, offer to universities the possibility to develop a new model in line with the European environment, focusing on quality aims and adapting to the socioeconomic current challenges. A new educational model centered on the student, on the formation of specific and transverse competitions, on the improvement of the employability and the access to the labor market, on the attraction and fixation of talent, is an indispensable condition for the effective social mobility and for the homogeneous development of a more responsible and sustainable socioeconomic and productive model

Parabolic and quasiparabolic subgroups of free partially commutative groups

Let Γ be a finite graph and G be the corresponding free partially commutative group. In this paper we study subgroups generated by vertices of the graph Γ, which we call canonical parabolic subgroups. A natural extension of the definition leads to canonical quasiparabolic subgroups. It is shown that the centralisers of subsets of G are the conjugates of canonical quasiparabolic centralisers satisfying certain graph theoretic conditions.

Stock market volatility and learning

Introducing bounded rationality in a standard consumption-based asset pricing model with time separable preferences strongly improves empirical performance. Learning causes momentum and mean reversion of returns and thereby excess volatility, persistence of price-dividend ratios, long-horizon return predictability and a risk premium, as in the habit model of Campbell and Cochrane (1999), but for lower risk aversion. This is obtained, even though our learning scheme introduces just one free parameter and we only consider learning schemes that imply small deviations from full rationality. The findings are robust to the learning rule used and other model features. What is key is that agents forecast future stock prices using past information on prices.

Implementació d'un demostrador wireless: network cording i virtualització d'interfícies sense fils

El treball realitzat en aquest projecte es basa en l'implementació d'un demostrador wireless, i més específicament, en l'estudi de les tècniques network coding i virtualització. Network coding és un nou mètode de transmissió de dades que es basa en la codificació de paquets per incrementar el rendiment fins ara obtingut als mètodes de transmissió convencionals. La virtualització és una tècnica que consisteix en compartir de forma més eficient els recursos d'un sistema. En el nostre cas s'utilitzarà la virtualització per dividir una interfície sense fils en diferents usuaris virtuals transmetent i rebent dades simultàniament. L'objectiu del projecte és realitzar un seguit de proves i estudis per veure els avantatges d'aquestes dues tècniques.

Deliberative ecological economics: emergence and research issues

We discuss the recent emergence of "deliberative ecological economics", a field that highlights the potential of deliberation for improving environmental governance. We locate the emergence of this literature in the long concern in ecological economics over the policy implications of limited views of human action and its encounter with deliberative democracy scholarship and the model of communicative rationality as an alternative to utilitarianism. Considering criticisms over methods used and the focus of research in deliberative decision-making, we put forward a research agenda for deliberative ecological economics. Given the promising potential of deliberative processes for improving the effectiveness and legitimacy of environmental decision-making, work in this area could help advance both theory and practice in environmental governance.

The Peace Processes in the Basque Country and Northern Ireland (1994-2006): a Comparative Approach

The peace process in Northern Ireland demonstrates that new sovereignty formulas need to be explored in order to meet the demands of the populations and territories in conflict. The profound transformation of the classic symbolic elements of the nation-state within the context of the European Union has greatly contributed to the prospects for a resolution of this old conflict. Today’s discussions are focused on the search for instruments of shared sovereignty that are adapted to a complex and plural social reality. This new approach for finding a solution to the Irish conflict is particularly relevant to the Basque debate about formulating creative and modern solutions to similar conflicts over identity and sovereignty. The notion of shared sovereignty implemented in Northern Ireland –a formula for complex interdependent relations– is of significant relevance to the broader international community and is likely to become an increasingly potent and transcendent model for conflict resolution and peace building.

A Method and Tool to Support the Analysis and Enhance the Understanding of Peer-to-Peer Learning Experiences

In this paper we look at how a web-based social software can be used to make qualitative data analysis of online peer-to-peer learning experiences. Specifically, we propose to use Cohere, a web-based social sense-making tool, to observe, track, annotate and visualize discussion group activities in online courses. We define a specific methodology for data observation and structuring, and present results of the analysis of peer interactions conducted in discussion forum in a real case study of a P2PU course. Finally we discuss how network visualization and analysis can be used to gather a better understanding of the peer-to-peer learning experience. To do so, we provide preliminary insights on the social, dialogical and conceptual connections that have been generated within one online discussion group.

An ATM distributed simulator for network management research

Due to the high cost of a large ATM network working up to full strength to apply our ideas about network management, i.e., dynamic virtual path (VP) management and fault restoration, we developed a distributed simulation platform for performing our experiments. This platform also had to be capable of other sorts of tests, such as connection admission control (CAC) algorithms, routing algorithms, and accounting and charging methods. The platform was posed as a very simple, event-oriented and scalable simulation. The main goal was the simulation of a working ATM backbone network with a potentially large number of nodes (hundreds). As research into control algorithms and low-level, or rather cell-level methods, was beyond the scope of this study, the simulation took place at a connection level, i.e., there was no real traffic of cells. The simulated network behaved like a real network accepting and rejecting SNMP ones, or experimental tools using the API node

Application for fault location in electrical power distribution systems

Fault location has been studied deeply for transmission lines due to its importance in power systems. Nowadays the problem of fault location on distribution systems is receiving special attention mainly because of the power quality regulations. In this context, this paper presents an application software developed in Matlabtrade that automatically calculates the location of a fault in a distribution power system, starting from voltages and currents measured at the line terminal and the model of the distribution power system data. The application is based on a N-ary tree structure, which is suitable to be used in this application due to the highly branched and the non- homogeneity nature of the distribution systems, and has been developed for single-phase, two-phase, two-phase-to-ground, and three-phase faults. The implemented application is tested by using fault data in a real electrical distribution power system

Estimation of zero-sequence impedance of undergrounds cables for single-phase fault location in distribution systems with electric arc

This paper focus on the problem of locating single-phase faults in mixed distribution electric systems, with overhead lines and underground cables, using voltage and current measurements at the sending-end and sequence model of the network. Since calculating series impedance for underground cables is not as simple as in the case of overhead lines, the paper proposes a methodology to obtain an estimation of zero-sequence impedance of underground cables starting from previous single-faults occurred in the system, in which an electric arc occurred at the fault location. For this reason, the signal is previously pretreated to eliminate its peaks voltage and the analysis can be done working with a signal as close as a sinus wave as possible

Minimizing recombinations in consensus networks for phylogeographic studies

Background: We address the problem of studying recombinational variations in (human) populations. In this paper, our focus is on one computational aspect of the general task: Given two networks G1 and G2, with both mutation and recombination events, defined on overlapping sets of extant units the objective is to compute a consensus network G3 with minimum number of additional recombinations. We describe a polynomial time algorithm with a guarantee that the number of computed new recombination events is within ϵ = sz(G1, G2) (function sz is a well-behaved function of the sizes and topologies of G1 and G2) of the optimal number of recombinations. To date, this is the best known result for a network consensus problem.Results: Although the network consensus problem can be applied to a variety of domains, here we focus on structure of human populations. With our preliminary analysis on a segment of the human Chromosome X data we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. These results have been verified independently using traditional manual procedures. To the best of our knowledge, this is the first recombinations-based characterization of human populations. Conclusion: We show that our mathematical model identifies recombination spots in the individual haplotypes; the aggregate of these spots over a set of haplotypes defines a recombinational landscape that has enough signal to detect continental as well as population divide based on a short segment of Chromosome X. In particular, we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. The agreement with mutation-based analysis can be viewed as an indirect validation of our results and the model. Since the model in principle gives us more information embedded in the networks, in our future work, we plan to investigate more non-traditional questions via these structures computed by our methodology.