Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

TOPSIG : Topology Preserving Document Signatures

Performance comparisons between File Signatures and Inverted Files for text retrieval have previously shown several significant shortcomings of file signatures relative to inverted files. The inverted file approach underpins most state-of-the-art search engine algorithms, such as Language and Probabilistic models. It has been widely accepted that traditional file signatures are inferior alternatives to inverted files. This paper describes TopSig, a new approach to the construction of file signatures. Many advances in semantic hashing and dimensionality reduction have been made in recent times, but these were not so far linked to general purpose, signature file based, search engines. This paper introduces a different signature file approach that builds upon and extends these recent advances. We are able to demonstrate significant improvements in the performance of signature file based indexing and retrieval, performance that is comparable to that of state of the art inverted file based systems, including Language models and BM25. These findings suggest that file signatures offer a viable alternative to inverted files in suitable settings and positions the file signatures model in the class of Vector Space retrieval models.

Fourier active appearance models

Gaining invariance to camera and illumination variations has been a well investigated topic in Active Appearance Model (AAM) fitting literature. The major problem lies in the inability of the appearance parameters of the AAM to generalize to unseen conditions. An attractive approach for gaining invariance is to fit an AAM to a multiple filter response (e.g. Gabor) representation of the input image. Naively applying this concept with a traditional AAM is computationally prohibitive, especially as the number of filter responses increase. In this paper, we present a computationally efficient AAM fitting algorithm based on the Lucas-Kanade (LK) algorithm posed in the Fourier domain that affords invariance to both expression and illumination. We refer to this as a Fourier AAM (FAAM), and show that this method gives substantial improvement in person specific AAM fitting performance over traditional AAM fitting methods.

Semantic modeling method for configurable enterprise information systems

Business practices vary from one company to another and business practices often need to be changed due to changes of business environments. To satisfy different business practices, enterprise systems need to be customized. To keep up with ongoing business practice changes, enterprise systems need to be adapted. Because of rigidity and complexity, the customization and adaption of enterprise systems often takes excessive time with potential failures and budget shortfall. Moreover, enterprise systems often drag business behind because they cannot be rapidly adapted to support business practice changes. Extensive literature has addressed this issue by identifying success or failure factors, implementation approaches, and project management strategies. Those efforts were aimed at learning lessons from post implementation experiences to help future projects. This research looks into this issue from a different angle. It attempts to address this issue by delivering a systematic method for developing flexible enterprise systems which can be easily tailored for different business practices or rapidly adapted when business practices change. First, this research examines the role of system models in the context of enterprise system development; and the relationship of system models with software programs in the contexts of computer aided software engineering (CASE), model driven architecture (MDA) and workflow management system (WfMS). Then, by applying the analogical reasoning method, this research initiates a concept of model driven enterprise systems. The novelty of model driven enterprise systems is that it extracts system models from software programs and makes system models able to stay independent of software programs. In the paradigm of model driven enterprise systems, system models act as instructors to guide and control the behavior of software programs. Software programs function by interpreting instructions in system models. This mechanism exposes the opportunity to tailor such a system by changing system models. To make this true, system models should be represented in a language which can be easily understood by human beings and can also be effectively interpreted by computers. In this research, various semantic representations are investigated to support model driven enterprise systems. The significance of this research is 1) the transplantation of the successful structure for flexibility in modern machines and WfMS to enterprise systems; and 2) the advancement of MDA by extending the role of system models from guiding system development to controlling system behaviors. This research contributes to the area relevant to enterprise systems from three perspectives: 1) a new paradigm of enterprise systems, in which enterprise systems consist of two essential elements: system models and software programs. These two elements are loosely coupled and can exist independently; 2) semantic representations, which can effectively represent business entities, entity relationships, business logic and information processing logic in a semantic manner. Semantic representations are the key enabling techniques of model driven enterprise systems; and 3) a brand new role of system models; traditionally the role of system models is to guide developers to write system source code. This research promotes the role of system models to control the behaviors of enterprise.

The impact of software-as-a-service on business models of leading software vendors : experiences from three exploratory case studies

The number of software vendors offering ‘Software-as-a-Service’ has been increasing in recent years. In the Software-as-a-Service model software is operated by the software vendor and delivered to the customer as a service. Existing business models and industry structures are challenged by the changes to the deployment and pricing model compared to traditional software. However, the full implications on the way companies create, deliver and capture value are not yet sufficiently analyzed. Current research is scattered on specific aspects, only a few studies provide a more holistic view of the impact from a business model perspective. For vendors it is, however, crucial to be aware of the potentially far reaching consequences of Software-as-a-Service. Therefore, a literature review and three exploratory case studies of leading software vendors are used to evaluate possible implications of Software-as-a-Service on business models. The results show an impact on all business model building blocks and highlight in particular the often less articulated impact on key activities, customer relationship and key partnerships for leading software vendors and show related challenges, for example, with regard to the integration of development and operations processes. The observed implications demonstrate the disruptive character of the concept and identify future research requirements.

Information extraction from web services : a comparison of Tokenisation algorithms

Most web service discovery systems use keyword-based search algorithms and, although partially successful, sometimes fail to satisfy some users information needs. This has given rise to several semantics-based approaches that look to go beyond simple attribute matching and try to capture the semantics of services. However, the results reported in the literature vary and in many cases are worse than the results obtained by keyword-based systems. We believe the accuracy of the mechanisms used to extract tokens from the non-natural language sections of WSDL files directly affects the performance of these techniques, because some of them can be more sensitive to noise. In this paper three existing tokenization algorithms are evaluated and a new algorithm that outperforms all the algorithms found in the literature is introduced.

Evaluating medical information retrieval

This paper presents a framework for evaluating information retrieval of medical records. We use the BLULab corpus, a large collection of real-world de-identified medical records. The collection has been hand coded by clinical terminol- ogists using the ICD-9 medical classification system. The ICD codes are used to devise queries and relevance judge- ments for this collection. Results of initial test runs using a baseline IR system are provided. Queries and relevance judgements are online to aid further research in medical IR. Please visit: http://koopman.id.au/med_eval.

A comparison of alternative bankruptcy prediction models

Early models of bankruptcy prediction employed financial ratios drawn from pre-bankruptcy financial statements and performed well both in-sample and out-of-sample. Since then there has been an ongoing effort in the literature to develop models with even greater predictive performance. A significant innovation in the literature was the introduction into bankruptcy prediction models of capital market data such as excess stock returns and stock return volatility, along with the application of the Black–Scholes–Merton option-pricing model. In this note, we test five key bankruptcy models from the literature using an upto- date data set and find that they each contain unique information regarding the probability of bankruptcy but that their performance varies over time. We build a new model comprising key variables from each of the five models and add a new variable that proxies for the degree of diversification within the firm. The degree of diversification is shown to be negatively associated with the risk of bankruptcy. This more general model outperforms the existing models in a variety of in-sample and out-of-sample tests.

The use of temporal speech and lip information for multi-modal speaker identification via multi-stream HMMs

Investigates the use of temporal lip information, in conjunction with speech information, for robust, text-dependent speaker identification. We propose that significant speaker-dependent information can be obtained from moving lips, enabling speaker recognition systems to be highly robust in the presence of noise. The fusion structure for the audio and visual information is based around the use of multi-stream hidden Markov models (MSHMM), with audio and visual features forming two independent data streams. Recent work with multi-modal MSHMMs has been performed successfully for the task of speech recognition. The use of temporal lip information for speaker identification has been performed previously (T.J. Wark et al., 1998), however this has been restricted to output fusion via single-stream HMMs. We present an extension to this previous work, and show that a MSHMM is a valid structure for multi-modal speaker identification

Stochastic models and simulation of ion channel dynamics

The behaviour of ion channels within cardiac and neuronal cells is intrinsically stochastic in nature. When the number of channels is small this stochastic noise is large and can have an impact on the dynamics of the system which is potentially an issue when modelling small neurons and drug block in cardiac cells. While exact methods correctly capture the stochastic dynamics of a system they are computationally expensive, restricting their inclusion into tissue level models and so approximations to exact methods are often used instead. The other issue in modelling ion channel dynamics is that the transition rates are voltage dependent, adding a level of complexity as the channel dynamics are coupled to the membrane potential. By assuming that such transition rates are constant over each time step, it is possible to derive a stochastic differential equation (SDE), in the same manner as for biochemical reaction networks, that describes the stochastic dynamics of ion channels. While such a model is more computationally efficient than exact methods we show that there are analytical problems with the resulting SDE as well as issues in using current numerical schemes to solve such an equation. We therefore make two contributions: develop a different model to describe the stochastic ion channel dynamics that analytically behaves in the correct manner and also discuss numerical methods that preserve the analytical properties of the model.

Some novel techniques of parameter estimation for the dynamical models in biological systems

Inverse problems based on using experimental data to estimate unknown parameters of a system often arise in biological and chaotic systems. In this paper, we consider parameter estimation in systems biology involving linear and non-linear complex dynamical models, including the Michaelis–Menten enzyme kinetic system, a dynamical model of competence induction in Bacillus subtilis bacteria and a model of feedback bypass in B. subtilis bacteria. We propose some novel techniques for inverse problems. Firstly, we establish an approximation of a non-linear differential algebraic equation that corresponds to the given biological systems. Secondly, we use the Picard contraction mapping, collage methods and numerical integration techniques to convert the parameter estimation into a minimization problem of the parameters. We propose two optimization techniques: a grid approximation method and a modified hybrid Nelder–Mead simplex search and particle swarm optimization (MH-NMSS-PSO) for non-linear parameter estimation. The two techniques are used for parameter estimation in a model of competence induction in B. subtilis bacteria with noisy data. The MH-NMSS-PSO scheme is applied to a dynamical model of competence induction in B. subtilis bacteria based on experimental data and the model for feedback bypass. Numerical results demonstrate the effectiveness of our approach.

Large scale participatory acoustic sensor data analysis : tools and reputation models to enhance effectiveness

Acoustic sensors play an important role in augmenting the traditional biodiversity monitoring activities carried out by ecologists and conservation biologists. With this ability however comes the burden of analysing large volumes of complex acoustic data. Given the complexity of acoustic sensor data, fully automated analysis for a wide range of species is still a significant challenge. This research investigates the use of citizen scientists to analyse large volumes of environmental acoustic data in order to identify bird species. Specifically, it investigates ways in which the efficiency of a user can be improved through the use of species identification tools and the use of reputation models to predict the accuracy of users with unidentified skill levels. Initial experimental results are reported.

Modelling the activation of words in human memory : the spreading activation, spooky-activation-at-a-distance and the entanglement models compared

Modelling how a word is activated in human memory is an important requirement for determining the probability of recall of a word in an extra-list cueing experiment. The spreading activation, spooky-action-at-a-distance and entanglement models have all been used to model the activation of a word. Recently a hypothesis was put forward that the mean activation levels of the respective models are as follows: Spreading � Entanglment � Spooking-action-at-a-distance This article investigates this hypothesis by means of a substantial empirical analysis of each model using the University of South Florida word association, rhyme and word norms.