Fuzzy methods for analysis of microarrays and networks

Bioinformatics involves analyses of biological data such as DNA sequences, microarrays and protein-protein interaction (PPI) networks. Its two main objectives are the identification of genes or proteins and the prediction of their functions. Biological data often contain uncertain and imprecise information. Fuzzy theory provides useful tools to deal with this type of information, hence has played an important role in analyses of biological data. In this thesis, we aim to develop some new fuzzy techniques and apply them on DNA microarrays and PPI networks. We will focus on three problems: (1) clustering of microarrays; (2) identification of disease-associated genes in microarrays; and (3) identification of protein complexes in PPI networks. The first part of the thesis aims to detect, by the fuzzy C-means (FCM) method, clustering structures in DNA microarrays corrupted by noise. Because of the presence of noise, some clustering structures found in random data may not have any biological significance. In this part, we propose to combine the FCM with the empirical mode decomposition (EMD) for clustering microarray data. The purpose of EMD is to reduce, preferably to remove, the effect of noise, resulting in what is known as denoised data. We call this method the fuzzy C-means method with empirical mode decomposition (FCM-EMD). We applied this method on yeast and serum microarrays, and the silhouette values are used for assessment of the quality of clustering. The results indicate that the clustering structures of denoised data are more reasonable, implying that genes have tighter association with their clusters. Furthermore we found that the estimation of the fuzzy parameter m, which is a difficult step, can be avoided to some extent by analysing denoised microarray data. The second part aims to identify disease-associated genes from DNA microarray data which are generated under different conditions, e.g., patients and normal people. We developed a type-2 fuzzy membership (FM) function for identification of diseaseassociated genes. This approach is applied to diabetes and lung cancer data, and a comparison with the original FM test was carried out. Among the ten best-ranked genes of diabetes identified by the type-2 FM test, seven genes have been confirmed as diabetes-associated genes according to gene description information in Gene Bank and the published literature. An additional gene is further identified. Among the ten best-ranked genes identified in lung cancer data, seven are confirmed that they are associated with lung cancer or its treatment. The type-2 FM-d values are significantly different, which makes the identifications more convincing than the original FM test. The third part of the thesis aims to identify protein complexes in large interaction networks. Identification of protein complexes is crucial to understand the principles of cellular organisation and to predict protein functions. In this part, we proposed a novel method which combines the fuzzy clustering method and interaction probability to identify the overlapping and non-overlapping community structures in PPI networks, then to detect protein complexes in these sub-networks. Our method is based on both the fuzzy relation model and the graph model. We applied the method on several PPI networks and compared with a popular protein complex identification method, the clique percolation method. For the same data, we detected more protein complexes. We also applied our method on two social networks. The results showed our method works well for detecting sub-networks and give a reasonable understanding of these communities.

Multifractal characterisation and analysis of complex networks

Complex networks have been studied extensively due to their relevance to many real-world systems such as the world-wide web, the internet, biological and social systems. During the past two decades, studies of such networks in different fields have produced many significant results concerning their structures, topological properties, and dynamics. Three well-known properties of complex networks are scale-free degree distribution, small-world effect and self-similarity. The search for additional meaningful properties and the relationships among these properties is an active area of current research. This thesis investigates a newer aspect of complex networks, namely their multifractality, which is an extension of the concept of selfsimilarity. The first part of the thesis aims to confirm that the study of properties of complex networks can be expanded to a wider field including more complex weighted networks. Those real networks that have been shown to possess the self-similarity property in the existing literature are all unweighted networks. We use the proteinprotein interaction (PPI) networks as a key example to show that their weighted networks inherit the self-similarity from the original unweighted networks. Firstly, we confirm that the random sequential box-covering algorithm is an effective tool to compute the fractal dimension of complex networks. This is demonstrated on the Homo sapiens and E. coli PPI networks as well as their skeletons. Our results verify that the fractal dimension of the skeleton is smaller than that of the original network due to the shortest distance between nodes is larger in the skeleton, hence for a fixed box-size more boxes will be needed to cover the skeleton. Then we adopt the iterative scoring method to generate weighted PPI networks of five species, namely Homo sapiens, E. coli, yeast, C. elegans and Arabidopsis Thaliana. By using the random sequential box-covering algorithm, we calculate the fractal dimensions for both the original unweighted PPI networks and the generated weighted networks. The results show that self-similarity is still present in generated weighted PPI networks. This implication will be useful for our treatment of the networks in the third part of the thesis. The second part of the thesis aims to explore the multifractal behavior of different complex networks. Fractals such as the Cantor set, the Koch curve and the Sierspinski gasket are homogeneous since these fractals consist of a geometrical figure which repeats on an ever-reduced scale. Fractal analysis is a useful method for their study. However, real-world fractals are not homogeneous; there is rarely an identical motif repeated on all scales. Their singularity may vary on different subsets; implying that these objects are multifractal. Multifractal analysis is a useful way to systematically characterize the spatial heterogeneity of both theoretical and experimental fractal patterns. However, the tools for multifractal analysis of objects in Euclidean space are not suitable for complex networks. In this thesis, we propose a new box covering algorithm for multifractal analysis of complex networks. This algorithm is demonstrated in the computation of the generalized fractal dimensions of some theoretical networks, namely scale-free networks, small-world networks, random networks, and a kind of real networks, namely PPI networks of different species. Our main finding is the existence of multifractality in scale-free networks and PPI networks, while the multifractal behaviour is not confirmed for small-world networks and random networks. As another application, we generate gene interactions networks for patients and healthy people using the correlation coefficients between microarrays of different genes. Our results confirm the existence of multifractality in gene interactions networks. This multifractal analysis then provides a potentially useful tool for gene clustering and identification. The third part of the thesis aims to investigate the topological properties of networks constructed from time series. Characterizing complicated dynamics from time series is a fundamental problem of continuing interest in a wide variety of fields. Recent works indicate that complex network theory can be a powerful tool to analyse time series. Many existing methods for transforming time series into complex networks share a common feature: they define the connectivity of a complex network by the mutual proximity of different parts (e.g., individual states, state vectors, or cycles) of a single trajectory. In this thesis, we propose a new method to construct networks of time series: we define nodes by vectors of a certain length in the time series, and weight of edges between any two nodes by the Euclidean distance between the corresponding two vectors. We apply this method to build networks for fractional Brownian motions, whose long-range dependence is characterised by their Hurst exponent. We verify the validity of this method by showing that time series with stronger correlation, hence larger Hurst exponent, tend to have smaller fractal dimension, hence smoother sample paths. We then construct networks via the technique of horizontal visibility graph (HVG), which has been widely used recently. We confirm a known linear relationship between the Hurst exponent of fractional Brownian motion and the fractal dimension of the corresponding HVG network. In the first application, we apply our newly developed box-covering algorithm to calculate the generalized fractal dimensions of the HVG networks of fractional Brownian motions as well as those for binomial cascades and five bacterial genomes. The results confirm the monoscaling of fractional Brownian motion and the multifractality of the rest. As an additional application, we discuss the resilience of networks constructed from time series via two different approaches: visibility graph and horizontal visibility graph. Our finding is that the degree distribution of VG networks of fractional Brownian motions is scale-free (i.e., having a power law) meaning that one needs to destroy a large percentage of nodes before the network collapses into isolated parts; while for HVG networks of fractional Brownian motions, the degree distribution has exponential tails, implying that HVG networks would not survive the same kind of attack.

Success and failure factors of shared services : an IS literature analysis

Organizations seeking improvements in their performance are increasingly exploring alternative models and approaches for providing support services; one such approach being Shared Services. Because of the possible consequential impact of Shared Services on organizations, and given that information systems (IS) is both an enabler of Shared Services (for other functional areas) as well as a promising area for Shared Services application, Shared Services is an important area for research in the IS field. Though Shared Services has been extensively adopted on the promise of economies of scale and scope, factors of Shared Services success (or failure) have received little research attention. This paper reports the distillation of success and failure factors of Shared Services from an IS perspective. Employing NVIVO and content analysis of 158 selected articles, 9 key success factors and 5 failure factors are identified, suggesting important implications for practice and further research.

Continuing the critical analysis of 'meaningful relationships' in the context of the 'twin pillars'

This article continues the critical analysis of ‘meaningful relationships’ in the context of the operation of the ‘twin pillars’ which underpin the parenting provisions. It will be argued that the attitude of judicial officers to three key questions influence how they interpret this concept and consequently apply the best interest considerations. Relevant to this discussion is an examination of the Full Court’s approach to the key parenting sections, particularly the interaction of the primary and additional considerations. Against this backdrop, a current proposal to amend the ‘twin pillars’ will be examined.

Participatory analysis of mobile diaries to inform the design of ridesharing systems

In many “user centred design” methods, participants are used as informants to provide data but they are not involved in further analysis of that data. This paper investigates a participatory analysis approach in order to identify the strengths and weaknesses of involving participants collaboratively in the requirements analysis process. Findings show that participants are able to use information that they themselves have provided to analyse requirements and to draw upon that analysis for design, producing insights and suggestions that might not have been available otherwise to the design team. The contribution of this paper is to demonstrate an example of a participatory analysis process.

Relevance feature discovery for text analysis

It is a big challenge to guarantee the quality of discovered relevance features in text documents for describing user preferences because of the large number of terms, patterns, and noise. Most existing popular text mining and classification methods have adopted term-based approaches. However, they have all suffered from the problems of polysemy and synonymy. Over the years, people have often held the hypothesis that pattern-based methods should perform better than term- based ones in describing user preferences, but many experiments do not support this hypothesis. This research presents a promising method, Relevance Feature Discovery (RFD), for solving this challenging issue. It discovers both positive and negative patterns in text documents as high-level features in order to accurately weight low-level features (terms) based on their specificity and their distributions in the high-level features. The thesis also introduces an adaptive model (called ARFD) to enhance the exibility of using RFD in adaptive environment. ARFD automatically updates the system's knowledge based on a sliding window over new incoming feedback documents. It can efficiently decide which incoming documents can bring in new knowledge into the system. Substantial experiments using the proposed models on Reuters Corpus Volume 1 and TREC topics show that the proposed models significantly outperform both the state-of-the-art term-based methods underpinned by Okapi BM25, Rocchio or Support Vector Machine and other pattern-based methods.

Determination of stress-strain characteristics of railhead steel using image analysis

True stress-strain curve of railhead steel is required to investigate the behaviour of railhead under wheel loading through elasto-plastic Finite Element (FE) analysis. To reduce the rate of wear, the railhead material is hardened through annealing and quenching. The Australian standard rail sections are not fully hardened and hence suffer from non-uniform distribution of the material property; usage of average properties in the FE modelling can potentially induce error in the predicted plastic strains. Coupons obtained at varying depths of the railhead were, therefore, tested under axial tension and the strains were measured using strain gauges as well as an image analysis technique, known as the Particle Image Velocimetry (PIV). The head hardened steel exhibit existence of three distinct zones of yield strength; the yield strength as the ratio of the average yield strength provided in the standard (σyr=780MPa) and the corresponding depth as the ratio of the head hardened zone along the axis of symmetry are as follows: (1.17 σyr, 20%), (1.06 σyr, 20%- 80%) and (0.71 σyr, > 80%). The stress-strain curves exhibit limited plastic zone with fracture occurring at strain less than 0.1.

An analysis of the qualitative characteristics of management commentary reporting by New Zealand companies

The narrative section of annual reports has considerable value to its user groups, such as financial analysts and investors (Tiexiera, 2004; Barlett and Chandler, 1997, IASB, 2006). This narrative section including chairpersons’/presidents’ statement contains twice the quantity of information than the financial statements section (Smith and Taffler, 2000). However, the abundance of information does not necessarily enhance the quality of such information (IASB, 2006). This issue of qualitative characteristics has been long foregone by researchers. This issue has attracted the attention of IASB (2006). Following the dearth in research in regard to qualitative characteristics of reporting this paper explores whether investors’ required qualitative characteristics as outlined by the IASB (2006) have been satisfied in management commentary section of New Zealand companies’ annual reports. Our result suggests that the principal stakeholders’, that is, investors’ qualitative characteristics requirements have been partially met in this section of annual reports. The qualitative characteristic of ‘relevance’ and ‘supportability’ have been satisfied in more annual reports compared to that of ‘balance’ and ‘comparability.’

Scaling analysis of natural convection boundary layers : Application to attic space

The natural convection thermal boundary layer adjacent to an inclined flat plate and inclined walls of an attic space subject to instantaneous and ramp heating and cooling is investigated. A scaling analysis has been performed to describe the flow behaviour and heat transfer. Major scales quantifying the flow velocity, flow development time, heat transfer and the thermal and viscous boundary layer thicknesses at different stages of the flow development are established. Scaling relations of heating-up and cooling-down times and heat transfer rates have also been reported for the case of attic space. The scaling relations have been verified by numerical simulations over a wide range of parameters. Further, a periodic temperature boundary condition is also considered to show the flow features in the attic space over diurnal cycles.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

A Bayesian analysis of an agricultural field trial with three spatial dimensions

Modern technology now has the ability to generate large datasets over space and time. Such data typically exhibit high autocorrelations over all dimensions. The field trial data motivating the methods of this paper were collected to examine the behaviour of traditional cropping and to determine a cropping system which could maximise water use for grain production while minimising leakage below the crop root zone. They consist of moisture measurements made at 15 depths across 3 rows and 18 columns, in the lattice framework of an agricultural field. Bayesian conditional autoregressive (CAR) models are used to account for local site correlations. Conditional autoregressive models have not been widely used in analyses of agricultural data. This paper serves to illustrate the usefulness of these models in this field, along with the ease of implementation in WinBUGS, a freely available software package. The innovation is the fitting of separate conditional autoregressive models for each depth layer, the ‘layered CAR model’, while simultaneously estimating depth profile functions for each site treatment. Modelling interest also lay in how best to model the treatment effect depth profiles, and in the choice of neighbourhood structure for the spatial autocorrelation model. The favoured model fitted the treatment effects as splines over depth, and treated depth, the basis for the regression model, as measured with error, while fitting CAR neighbourhood models by depth layer. It is hierarchical, with separate onditional autoregressive spatial variance components at each depth, and the fixed terms which involve an errors-in-measurement model treat depth errors as interval-censored measurement error. The Bayesian framework permits transparent specification and easy comparison of the various complex models compared.

Determining the appropriate proportion of owner-provided design in design-build contracts - a content analysis approach

The Request For Proposal (RFP) with the design‐build (DB) procurement arrangement is a document in which an owner develops his requirements and conveys the project scope to DB contractors. Owners should provide an appropriate level of design in DB RFPs to adequately describe their requirements without compromising the prospects for innovation. This paper examines and compares the different levels of owner‐provided design in DB RFPs by the content analysis of 84 requests for RFPs for public DB projects advertised between 2000 and 2010 with an aggregate contract value of over $5.4 billion. A statistical analysis was also conducted in order to explore the relationship between the proportion of owner‐provided design and other project information, including project type, advertisement time, project size, contractor selection method, procurement process and contract type. The results show that the majority (64.8%) of the RFPs provide less than 10% of the owner‐provided design. The owner‐provided design proportion has a significant association with project type, project size, contractor selection method and contract type. In addition, owners are generally providing less design in recent years than hitherto. The research findings also provide owners with perspectives to determine the appropriate level of owner‐provided design in DB RFPs.

Investing in the future : analysis of TxDOT 1547 Over-Axle Weight Tolerance Permits

The trucking industry has played a significant role in the economic growth in Texas by transporting and distributing commodities using commercial motor vehicles. The Texas Department of Transportation (TxDOT), however, has recognized that the large number of overweight trucks operating on the state highway system has resulted in the deterioration of pavement condition. In addition, the permit fee to carry higher loads above legal limits is much lower than the cost to treat the increase in pavement damage. The primary purpose of the research presented in this paper is to investigate current TxDOT overweight permit structures to support pavement management. The research team analyzed the TxDOT “1547” Over-axle Weight Tolerance Permit structure to support an increase in the fee structure, bringing it more in line with the actual pavement damage. The analysis showed that the revised overweight permit structure could provide an additional $9.3 million annually for pavement maintenance needs by increasing current permit fees. These results were supported by the 2030 Committee for recommendation to the Texas Transportation Commission and consideration by the State Legislature [1]. The research team recommends conducting further research to identify methods for working cooperatively with the trucking industry to develop improved methods for assessing weight damage relationships and developing more effective and accurate means for assessing overweight permit fees.

Analysis of electromagnetic forces in high voltage superconducting fault current limiters with saturated core

This paper presents a three-dimensional numerical analysis of the electromagnetic forces within a high voltage superconducting Fault Current Limiter (FCL) with a saturated core under short-circuit conditions. The effects of electrodynamics forces in power transformer coils under short-circuit conditions have been reported widely. However, the coil arrangement in an FCL with saturated core differs significantly from existing reactive devices. The boundary element method is employed to perform an electromagnetic force analysis on an FCL. The analysis focuses on axial and radial forces of the AC coil. The results are compared to those of a power transformer and important design considerations are highlighted.

Infrastructure charges and increases to new house prices : a preliminary analysis of the US empirical models

Sourcing appropriate funding for the provision of new urban infrastructure has been a policy dilemma for governments around the world for decades. This is particularly relevant in high growth areas where new services are required to support swelling populations. The Australian infrastructure funding policy dilemmas are reflective of similar matters in many countries, particularly the United States of America, where infrastructure cost recovery policies have been in place since the 1970’s. There is an extensive body of both theoretical and empirical literature from these countries that discusses the passing on (to home buyers) of these infrastructure charges, and the corresponding impact on housing prices. The theoretical evidence is consistent in its findings that infrastructure charges are passed on to home buyers by way of higher house prices. The empirical evidence is also consistent in its findings, with “overshifting” of these charges evident in all models since the 1980’s, i.e. $1 infrastructure charge results in greater than $1 increase in house prices. However, despite over a dozen separate studies over two decades in the US on this topic, no empirical works have been carried out in Australia to test if similar shifting or overshifting occurs here. The purpose of this research is to conduct a preliminary analysis of the more recent models used in these US empirical studies in order to identify the key study area selection criteria and success factors. The paper concludes that many of the study area selection criteria are implicit rather than explicit. By collecting data across the models, some implicit criteria become apparent, whilst others remain elusive. This data will inform future research on whether an existing model can be adopted or adapted for use in Australia.