874 research outputs found

    Bayesian Models for Gene Regulatory Networks Applied to Cancer Tissues

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    Cellular behavior is controlled through multivariate interactions between various biological molecules such as proteins and DNA. Various methods have previously been proposed to model such interactions. However many of these methods require large volumes of data to effectively estimate the associated unknown parameters. In this work we explore the use of Bayesian methods to exploit the prior knowledge about pathway information in combination with collected data in order to make accurate and useful inferences about tissue level behavior. These predictions would in turn help in the discovery of better therapeutic strategies such as the development of better combination therapies involving kinase inhibiting drugs. Various problems of modeling cancerous and healthy tissues from a Bayesian perspective have been addressed in this work. We give a short description of these problems here in this section. An important problem in the study of cancer is the understanding of the heterogeneous nature of the cell population. The clonal evolution of the tumor cells results in the tumors being composed of multiple sub-populations. Each sub-population reacts differently to any given therapy. This calls for the development of novel (regulatory network) models, which can accommodate heterogeneity in cancerous tissues. Here we present a new approach to model heterogeneity in cancer. We model heterogeneity as an ensemble of deterministic Boolean networks based on prior pathway knowledge. We develop the model considering the use of qPCR data. By observing gene expressions when the tissue is subjected to various stimuli, the compositional breakup of the tissue under study can be determined. We demonstrate the viability of this approach by using our model on synthetic data, and real world data collected from fibroblasts. Another problem which is addressed in this work is the determination of locations of dysregulations in a Boolean network used to model signal transduction networks. Knowledge about which proteins/genes are dysregulated in a regulatory network, such as in the Mitogen Activated Protein Kinase (MAPK) Network, can be used not only to decide upon which therapy to use for a particular case of cancer, but also help in discovering effective targets for new drugs. The posterior inference problem is solved using a version of the message passing algorithm. We have done simulation experiments on synthetic data to verify the efficacy of the algorithm as compared to the results from the much more computationally intensive Markov Chain Monte-Carlo methods. We also applied the model to analyze data collected from fibroblasts, thereby demonstrating how this model can be used on real world data. Another important issue in Bayesian computation is that the processing of the collected data must be done as efficiently as possible in terms of computational speed and memory requirements. The use of Markov Chain Monte Carlo methods is time consuming and hence other methods need to be used for the analysis. The use of conjugate exponential models is investigated in the modeling of the heterogeneity of cancerous tissues where variational methods could be used in a straightforward manner. Variational algorithms, which allow for the fast computations of posterior probability distributions of variables of interest, have been used in the inference of the compositional breakup of the heterogeneous tissue under study. The efficacy of these methods has been demonstrated by comparing them with other methods such as Markov chain Monte Carlo and Expectation maximization

    Optimal fault-tolerant placement of relay nodes in a mission critical wireless network

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    The operations of many critical infrastructures (e.g., airports) heavily depend on proper functioning of the radio communication network supporting operations. As a result, such a communication network is indeed a mission-critical communication network that needs adequate protection from external electromagnetic interferences. This is usually done through radiogoniometers. Basically, by using at least three suitably deployed radiogoniometers and a gateway gathering information from them, sources of electromagnetic emissions that are not supposed to be present in the monitored area can be localised. Typically, relay nodes are used to connect radiogoniometers to the gateway. As a result, some degree of fault-tolerance for the network of relay nodes is essential in order to offer a reliable monitoring. On the other hand, deployment of relay nodes is typically quite expensive. As a result, we have two conflicting requirements: minimise costs while guaranteeing a given fault-tolerance. In this paper address the problem of computing a deployment for relay nodes that minimises the relay node network cost while at the same time guaranteeing proper working of the network even when some of the relay nodes (up to a given maximum number) become faulty (fault-tolerance). We show that the above problem can be formulated as a Mixed Integer Linear Programming (MILP) as well as a Pseudo-Boolean Satisfiability (PB-SAT) optimisation problem and present experimental results com- paring the two approaches on realistic scenarios

    Online adaptation in Boolean network robots

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    Questa tesi si concentra su molteplici processi di adattamento online utilizzati su un robot autonomo, che è controllato da una rete booleana; l’obiettivo è adattare il suo comportamento ad un ambiente e ad un compito specifici. I risultati mostrano che il robot può adattarsi per navigare l’ambiente ed evitare le collisioni, seguendo inoltre un altro robot in movimento; riesce anche a generalizzare, quando posizionato in un’arena diversa rispetto a quella usata in allenamento. Con due dei processi di adattamento testati, il robot può esprimere più fenotipi (comportamenti) dallo stesso genotipo (nodi e connessioni della rete booleana), ottenendo così la plasticità fenotipica. Ciò si ottiene modificando l’accoppiamento tra i sensori o gli attuatori del robot con la rete

    Dagstuhl Reports : Volume 1, Issue 2, February 2011

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    Online Privacy: Towards Informational Self-Determination on the Internet (Dagstuhl Perspectives Workshop 11061) : Simone Fischer-Hübner, Chris Hoofnagle, Kai Rannenberg, Michael Waidner, Ioannis Krontiris and Michael Marhöfer Self-Repairing Programs (Dagstuhl Seminar 11062) : Mauro Pezzé, Martin C. Rinard, Westley Weimer and Andreas Zeller Theory and Applications of Graph Searching Problems (Dagstuhl Seminar 11071) : Fedor V. Fomin, Pierre Fraigniaud, Stephan Kreutzer and Dimitrios M. Thilikos Combinatorial and Algorithmic Aspects of Sequence Processing (Dagstuhl Seminar 11081) : Maxime Crochemore, Lila Kari, Mehryar Mohri and Dirk Nowotka Packing and Scheduling Algorithms for Information and Communication Services (Dagstuhl Seminar 11091) Klaus Jansen, Claire Mathieu, Hadas Shachnai and Neal E. Youn

    Structure and topology of transcriptional regulatory networks and their applications in bio-inspired networking

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    Biological networks carry out vital functions necessary for sustenance despite environmental adversities. Transcriptional Regulatory Network (TRN) is one such biological network that is formed due to the interaction between proteins, called Transcription Factors (TFs), and segments of DNA, called genes. TRNs are known to exhibit functional robustness in the face of perturbation or mutation: a property that is proven to be a result of its underlying network topology. In this thesis, we first propose a three-tier topological characterization of TRN to analyze the interplay between the significant graph-theoretic properties of TRNs such as scale-free out-degree distribution, low graph density, small world property and the abundance of subgraphs called motifs. Specifically, we pinpoint the role of a certain three-node motif, called Feed Forward Loop (FFL) motif in topological robustness as well as information spread in TRNs. With the understanding of the TRN topology, we explore its potential use in design of fault-tolerant communication topologies. To this end, we first propose an edge rewiring mechanism that remedies the vulnerability of TRNs to the failure of well-connected nodes, called hubs, while preserving its other significant graph-theoretic properties. We apply the rewired TRN topologies in the design of wireless sensor networks that are less vulnerable to targeted node failure. Similarly, we apply the TRN topology to address the issues of robustness and energy-efficiency in the following networking paradigms: robust yet energy-efficient delay tolerant network for post disaster scenarios, energy-efficient data-collection framework for smart city applications and a data transfer framework deployed over a fog computing platform for collaborative sensing --Abstract, page iii

    Proceedings of the Second NASA Formal Methods Symposium

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    This publication contains the proceedings of the Second NASA Formal Methods Symposium sponsored by the National Aeronautics and Space Administration and held in Washington D.C. April 13-15, 2010. Topics covered include: Decision Engines for Software Analysis using Satisfiability Modulo Theories Solvers; Verification and Validation of Flight-Critical Systems; Formal Methods at Intel -- An Overview; Automatic Review of Abstract State Machines by Meta Property Verification; Hardware-independent Proofs of Numerical Programs; Slice-based Formal Specification Measures -- Mapping Coupling and Cohesion Measures to Formal Z; How Formal Methods Impels Discovery: A Short History of an Air Traffic Management Project; A Machine-Checked Proof of A State-Space Construction Algorithm; Automated Assume-Guarantee Reasoning for Omega-Regular Systems and Specifications; Modeling Regular Replacement for String Constraint Solving; Using Integer Clocks to Verify the Timing-Sync Sensor Network Protocol; Can Regulatory Bodies Expect Efficient Help from Formal Methods?; Synthesis of Greedy Algorithms Using Dominance Relations; A New Method for Incremental Testing of Finite State Machines; Verification of Faulty Message Passing Systems with Continuous State Space in PVS; Phase Two Feasibility Study for Software Safety Requirements Analysis Using Model Checking; A Prototype Embedding of Bluespec System Verilog in the PVS Theorem Prover; SimCheck: An Expressive Type System for Simulink; Coverage Metrics for Requirements-Based Testing: Evaluation of Effectiveness; Software Model Checking of ARINC-653 Flight Code with MCP; Evaluation of a Guideline by Formal Modelling of Cruise Control System in Event-B; Formal Verification of Large Software Systems; Symbolic Computation of Strongly Connected Components Using Saturation; Towards the Formal Verification of a Distributed Real-Time Automotive System; Slicing AADL Specifications for Model Checking; Model Checking with Edge-valued Decision Diagrams; and Data-flow based Model Analysis
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