Probabilistic reasoning and inference for systems biology

One of the important challenges in Systems Biology is reasoning and performing hypotheses testing in uncertain conditions, when available knowledge may be incomplete and the experimental data may contain substantial noise. In this thesis we develop methods of probabilistic reasoning and inference that operate consistently within an environment of uncertain knowledge and data. Mechanistic mathematical models are used to describe hypotheses about biological systems. We consider both deductive model based reasoning and model inference from data. The main contributions are a novel modelling approach using continuous time Markov chains that enables deductive derivation of model behaviours and their properties, and the application of Bayesian inferential methods to solve the inverse problem of model inference and comparison, given uncertain knowledge and noisy data. In the first part of the thesis, we consider both individual and population based techniques for modelling biochemical pathways using continuous time Markov chains, and demonstrate why the latter is the most appropriate. We illustrate a new approach, based on symbolic intervals of concentrations, with an example portion of the ERK signalling pathway. We demonstrate that the resulting model approximates the same dynamic system as traditionally defined using ordinary differential equations. The advantage of the new approach is quantitative logical analysis; we formulate a number of biologically significant queries in the temporal logic CSL and use probabilistic symbolic model checking to investigate their veracity. In the second part of the thesis, we consider the inverse problem of model inference and testing of alternative hypotheses, when models are defined by non-linear ordinary differential equations and the experimental data is noisy and sparse. We compare and evaluate a number of statistical techniques, and implement an effective Bayesian inferential framework for systems biology based on Markov chain Monte Carlo methods and estimation of marginal likelihoods by annealing-melting integration. We illustrate the framework with two case studies, one of which involves an open problem concerning the mediation of ERK phosphorylation in the ERK pathway

Dispute Resolution Using Argumentation-Based Mediation

Mediation is a process, in which both parties agree to resolve their dispute by negotiating over alternative solutions presented by a mediator. In order to construct such solutions, mediation brings more information and knowledge, and, if possible, resources to the negotiation table. The contribution of this paper is the automated mediation machinery which does that. It presents an argumentation-based mediation approach that extends the logic-based approach to argumentation-based negotiation involving BDI agents. The paper describes the mediation algorithm. For comparison it illustrates the method with a case study used in an earlier work. It demonstrates how the computational mediator can deal with realistic situations in which the negotiating agents would otherwise fail due to lack of knowledge and/or resources.Comment: 6 page

Multi-Paradigm Reasoning for Access to Heterogeneous GIS

Accessing and querying geographical data in a uniform way has become easier in recent years. Emerging standards like WFS turn the web into a geospatial web services enabled place. Mediation architectures like VirGIS overcome syntactical and semantical heterogeneity between several distributed sources. On mobile devices, however, this kind of solution is not suitable, due to limitations, mostly regarding bandwidth, computation power, and available storage space. The aim of this paper is to present a solution for providing powerful reasoning mechanisms accessible from mobile applications and involving data from several heterogeneous sources. By adapting contents to time and location, mobile web information systems can not only increase the value and suitability of the service itself, but can substantially reduce the amount of data delivered to users. Because many problems pertain to infrastructures and transportation in general and to way finding in particular, one cornerstone of the architecture is higher level reasoning on graph networks with the Multi-Paradigm Location Language MPLL. A mediation architecture is used as a “graph provider” in order to transfer the load of computation to the best suited component – graph construction and transformation for example being heavy on resources. Reasoning in general can be conducted either near the “source” or near the end user, depending on the specific use case. The concepts underlying the proposal described in this paper are illustrated by a typical and concrete scenario for web applications

Benefits and challenges of applying Semantic Web Services in the e-Government domain

Joining up services in e-Government usually implies governmental agencies acting in concert without a central control regime. This requires the sharing of scattered and heterogeneous data. Semantic Web Service (SWS) technology can help to integrate, mediate and reason between these datasets. However, since few real-world applications have been developed, it is still unclear which are the actual benefits and issues of adopting such a technology in the e-Government domain. In this paper, we contribute to raising awareness of the potential benefits in the e-Government community by analyzing motivations, requirements, and expected results, before proposing a reusable SWS-based framework. We demonstrate the application of this framework by a compelling use case: a GIS-based emergency planning system. We illustrate the obtained benefits and the key challenges which remain to be addressed

Mediation of semantic web services in IRS-III

Business applications composed of heterogeneous distributed components or Web services need mediation to resolve data and process mismatches at runtime. This paper describes mediation in IRS-III, a framework and platform for developing WSMO-based Semantic Web Services. We present our approach to mediation within Semantic Web Services and highlight the role of WSMO mediator types when solving mismatches at the semantic level between a service requester and a service provider. We describe the components of our mediation framework and how it can handle data, goal and process mediation during the activities of selection, composition and invocation of Semantic Web Services

Semantic business process management: a vision towards using semantic web services for business process management

Business process management (BPM) is the approach to manage the execution of IT-supported business operations from a business expert's view rather than from a technical perspective. However, the degree of mechanization in BPM is still very limited, creating inertia in the necessary evolution and dynamics of business processes, and BPM does not provide a truly unified view on the process space of an organization. We trace back the problem of mechanization of BPM to an ontological one, i.e. the lack of machine-accessible semantics, and argue that the modeling constructs of semantic Web services frameworks, especially WSMO, are a natural fit to creating such a representation. As a consequence, we propose to combine SWS and BPM and create one consolidated technology, which we call semantic business process management (SBPM

Annotation of SBML Models Through Rule-Based Semantic Integration

*Motivation:* The creation of accurate quantitative Systems Biology Markup Language (SBML) models is a time-intensive, manual process often complicated by the many data sources and formats required to annotate even a small and well-scoped model. Ideally, the retrieval and integration of biological knowledge for model annotation should be performed quickly, precisely, and with a minimum of manual effort. Here, we present a method using off-the-shelf semantic web technology which enables this process: the heterogeneous data sources are first syntactically converted into ontologies; these are then aligned to a small domain ontology by applying a rule base. Integrating resources in this way can accommodate multiple formats with different semantics; it provides richly modelled biological knowledge suitable for annotation of SBML models.
*Results:* We demonstrate proof-of-principle for this rule-based mediation with two use cases for SBML model annotation. This was implemented with existing tools, decreasing development time and increasing reusability. This initial work establishes the feasibility of this approach as part of an automated SBML model annotation system.
*Availability:* Detailed information including download and mapping of the ontologies as well as integration results is available from "http://www.cisban.ac.uk/RBM":http://www.cisban.ac.uk/RB