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.

Improving the performance of facial expression recognition using dynamic, subtle and regional features

Human facial expression is a complex process characterized of dynamic, subtle and regional emotional features. State-of-the-art approaches on facial expression recognition (FER) have not fully utilized this kind of features to improve the recognition performance. This paper proposes an approach to overcome this limitation using patch-based ‘salient’ Gabor features. A set of 3D patches are extracted to represent the subtle and regional features, and then inputted into patch matching operations for capturing the dynamic features. Experimental results show a significant performance improvement of the proposed approach due to the use of the dynamic features. Performance comparison with pervious work also confirms that the proposed approach achieves the highest CRR reported to date on the JAFFE database and a top-level performance on the Cohn-Kanade (CK) database.

Dynamic response of distributed generators in a hybrid microgrid

A microgrid may be supplied from inertial (rotating type) and non-inertial (converter-interfaced) distributed generators (DGs). However the dynamic response of these two types of DGs is different. Inertial DGs have a slower response due to their governor characteristics while non inertial DGs have the ability to respond very quickly. The focus of this paper is to propose better controls using droop characteristics to improve the dynamic interaction between different DG types in an autonomous microgrid. The transient behavior of DGs in the microgrid is investigated during the DG synchronization and load changes. Power sharing strategies based on frequency and voltage droop are considered for DGs. Droop control strategies are proposed for DGs to improve the smooth synchronization and dynamic power sharing minimizing transient oscillations in the microgrid. Simulation studies are carried out on PSCAD for validation.

Urban maze : A typological investigation in porous morphology and dynamic pedestrian networks

Mixed use typologies and pedestrian networks are two strategies commonly applied in design of the contemporary city. These approaches, aimed towards the creation of a more sustainalble urban environment, have their roots in the traditional, pre-industrial towns; they characterize urban form, articulating the tension between privaate and public realms through a series of typological variations as well as stimulating commercial activity in the city centre. Arcades, loggias and verandas are just some of the elements which can mediate this tension. Historically they have defined physical and social spaces with particular character; in the contemporary city these features are applied to deform the urban form and create a porous, dynamic morphology. This paper, comparing case studies from Italy, Japan and Australia, investigates how the design of the transition zone can define hybrid pedestrian networks, where a clear distinction between the public and private realms is no longer applicable. Pedestrians use the city in a dynamic way, combining trajectories on the public street with ones on the fringe or inside of the private built environment. In some cases, cities offer different pedestrian network possibilities at different times, as the commercial precints are subject to variations in accessibility across various timeframes. These walkable systems have an impact on the urban form and identity of places, redefining typologies and requiring an in depth analysis through plan, section and elevation diagrams.

Learning the kernel matrix with semidefinite programming

Kernel-based learning algorithms work by embedding the data into a Euclidean space, and then searching for linear relations among the embedded data points. The embedding is performed implicitly, by specifying the inner products between each pair of points in the embedding space. This information is contained in the so-called kernel matrix, a symmetric and positive semidefinite matrix that encodes the relative positions of all points. Specifying this matrix amounts to specifying the geometry of the embedding space and inducing a notion of similarity in the input space - classical model selection problems in machine learning. In this paper we show how the kernel matrix can be learned from data via semidefinite programming (SDP) techniques. When applied to a kernel matrix associated with both training and test data this gives a powerful transductive algorithm -using the labeled part of the data one can learn an embedding also for the unlabeled part. The similarity between test points is inferred from training points and their labels. Importantly, these learning problems are convex, so we obtain a method for learning both the model class and the function without local minima. Furthermore, this approach leads directly to a convex method for learning the 2-norm soft margin parameter in support vector machines, solving an important open problem.

Learning the Kernel Matrix with Semi-Definite Programming

Kernel-based learning algorithms work by embedding the data into a Euclidean space, and then searching for linear relations among the embedded data points. The embedding is performed implicitly, by specifying the inner products between each pair of points in the embedding space. This information is contained in the so-called kernel matrix, a symmetric and positive definite matrix that encodes the relative positions of all points. Specifying this matrix amounts to specifying the geometry of the embedding space and inducing a notion of similarity in the input space -- classical model selection problems in machine learning. In this paper we show how the kernel matrix can be learned from data via semi-definite programming (SDP) techniques. When applied to a kernel matrix associated with both training and test data this gives a powerful transductive algorithm -- using the labelled part of the data one can learn an embedding also for the unlabelled part. The similarity between test points is inferred from training points and their labels. Importantly, these learning problems are convex, so we obtain a method for learning both the model class and the function without local minima. Furthermore, this approach leads directly to a convex method to learn the 2-norm soft margin parameter in support vector machines, solving another important open problem. Finally, the novel approach presented in the paper is supported by positive empirical results.

Stochastic models for regulatory networks of the genetic toggle switch

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.