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.

Structural damage identification with noise polluted Frequency Response Functions (FRFs)

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, very few attempts have been made to explore the structure damage with noise polluted data which is unavoidable effect in real world. The measurement data are contaminated by noise because of test environment as well as electronic devices and this noise tend to give error results with structural damage identification methods. Therefore it is important to investigate a method which can perform better with noise polluted data. This paper introduces a new damage index using principal component analysis (PCA) for damage detection of building structures being able to accept noise polluted frequency response functions (FRFs) as input. The FRF data are obtained from the function datagen of MATLAB program which is available on the web site of the IASC-ASCE (International Association for Structural Control– American Society of Civil Engineers) Structural Health Monitoring (SHM) Task Group. The proposed method involves a five-stage process: calculation of FRFs, calculation of damage index values using proposed algorithm, development of the artificial neural networks and introducing damage indices as input parameters and damage detection of the structure. This paper briefly describes the methodology and the results obtained in detecting damage in all six cases of the benchmark study with different noise levels. The proposed method is applied to a benchmark problem sponsored by the IASC-ASCE Task Group on Structural Health Monitoring, which was developed in order to facilitate the comparison of various damage identification methods. The illustrated results show that the PCA-based algorithm is effective for structural health monitoring with noise polluted FRFs which is of common occurrence when dealing with industrial structures.

Evolution of traffic management measures on road traffic noise

Road traffic noise affects the quality of life in the areas adjoining the road. The effect of traffic noise on people is wide ranging and may include sleep disturbance and negative impact on work efficiency. To address the problem of traffic noise, it is necessary to estimate the noise level. For this, a number of noise estimation models have been developed which can estimate noise at the receptor points, based on simple configuration of buildings. However, for a real world situation we have multiple buildings forming built-up area. In such a situation, it is almost impossible to consider multiple diffractions and reflections in sound propagation from the source to the receptor point. An engineering solution to such a real world problem is needed to estimate noise levels in built-up area.

Reduced sampling efficiency causes degraded Vernier hyperacuity with normal aging: Vernier acuity in position noise

Vernier acuity, a form of visual hyperacuity, is amongst the most precise forms of spatial vision. Under optimal conditions Vernier thresholds are much finer than the inter-photoreceptor distance. Achievement of such high precision is based substantially on cortical computations, most likely in the primary visual cortex. Using stimuli with added positional noise, we show that Vernier processing is reduced with advancing age across a wide range of noise levels. Using an ideal observer model, we are able to characterize the mechanisms underlying age-related loss, and show that the reduction in Vernier acuity can be mainly attributed to the reduction in efficiency of sampling, with no significant change in the level of internal position noise, or spatial distortion, in the visual system.

3D reconstruction of long bones utilising magnetic resonance imaging (MRI)

The design of pre-contoured fracture fixation implants (plates and nails) that correctly fit the anatomy of a patient utilises 3D models of long bones with accurate geometric representation. 3D data is usually available from computed tomography (CT) scans of human cadavers that generally represent the above 60 year old age group. Thus, despite the fact that half of the seriously injured population comes from the 30 year age group and below, virtually no data exists from these younger age groups to inform the design of implants that optimally fit patients from these groups. Hence, relevant bone data from these age groups is required. The current gold standard for acquiring such data–CT–involves ionising radiation and cannot be used to scan healthy human volunteers. Magnetic resonance imaging (MRI) has been shown to be a potential alternative in the previous studies conducted using small bones (tarsal bones) and parts of the long bones. However, in order to use MRI effectively for 3D reconstruction of human long bones, further validations using long bones and appropriate reference standards are required. Accurate reconstruction of 3D models from CT or MRI data sets requires an accurate image segmentation method. Currently available sophisticated segmentation methods involve complex programming and mathematics that researchers are not trained to perform. Therefore, an accurate but relatively simple segmentation method is required for segmentation of CT and MRI data. Furthermore, some of the limitations of 1.5T MRI such as very long scanning times and poor contrast in articular regions can potentially be reduced by using higher field 3T MRI imaging. However, a quantification of the signal to noise ratio (SNR) gain at the bone - soft tissue interface should be performed; this is not reported in the literature. As MRI scanning of long bones has very long scanning times, the acquired images are more prone to motion artefacts due to random movements of the subject‟s limbs. One of the artefacts observed is the step artefact that is believed to occur from the random movements of the volunteer during a scan. This needs to be corrected before the models can be used for implant design. As the first aim, this study investigated two segmentation methods: intensity thresholding and Canny edge detection as accurate but simple segmentation methods for segmentation of MRI and CT data. The second aim was to investigate the usability of MRI as a radiation free imaging alternative to CT for reconstruction of 3D models of long bones. The third aim was to use 3T MRI to improve the poor contrast in articular regions and long scanning times of current MRI. The fourth and final aim was to minimise the step artefact using 3D modelling techniques. The segmentation methods were investigated using CT scans of five ovine femora. The single level thresholding was performed using a visually selected threshold level to segment the complete femur. For multilevel thresholding, multiple threshold levels calculated from the threshold selection method were used for the proximal, diaphyseal and distal regions of the femur. Canny edge detection was used by delineating the outer and inner contour of 2D images and then combining them to generate the 3D model. Models generated from these methods were compared to the reference standard generated using the mechanical contact scans of the denuded bone. The second aim was achieved using CT and MRI scans of five ovine femora and segmenting them using the multilevel threshold method. A surface geometric comparison was conducted between CT based, MRI based and reference models. To quantitatively compare the 1.5T images to the 3T MRI images, the right lower limbs of five healthy volunteers were scanned using scanners from the same manufacturer. The images obtained using the identical protocols were compared by means of SNR and contrast to noise ratio (CNR) of muscle, bone marrow and bone. In order to correct the step artefact in the final 3D models, the step was simulated in five ovine femora scanned with a 3T MRI scanner. The step was corrected using the iterative closest point (ICP) algorithm based aligning method. The present study demonstrated that the multi-threshold approach in combination with the threshold selection method can generate 3D models from long bones with an average deviation of 0.18 mm. The same was 0.24 mm of the single threshold method. There was a significant statistical difference between the accuracy of models generated by the two methods. In comparison, the Canny edge detection method generated average deviation of 0.20 mm. MRI based models exhibited 0.23 mm average deviation in comparison to the 0.18 mm average deviation of CT based models. The differences were not statistically significant. 3T MRI improved the contrast in the bone–muscle interfaces of most anatomical regions of femora and tibiae, potentially improving the inaccuracies conferred by poor contrast of the articular regions. Using the robust ICP algorithm to align the 3D surfaces, the step artefact that occurred by the volunteer moving the leg was corrected, generating errors of 0.32 ± 0.02 mm when compared with the reference standard. The study concludes that magnetic resonance imaging, together with simple multilevel thresholding segmentation, is able to produce 3D models of long bones with accurate geometric representations. The method is, therefore, a potential alternative to the current gold standard CT imaging.

Study on road traffic noise prediction model taking into account the citywide network

For the further noise reduction in the future, the traffic management which controls traffic flow and physical distribution is important. To conduct the measure by the traffic management effectively, it is necessary to apply the model for predicting the traffic flow in the citywide road network. For this purpose, the existing model named AVENUE was used as a macro-traffic flow prediction model. The traffic flow model was integrated with the road vehicles' sound power model, and the new road traffic noise prediction model was established. By using this prediction model, the noise map of entire city can be made. In this study, first, the change of traffic flow on the road network after the establishment of new roads was estimated, and the change of the road traffic noise caused by the new roads was predicted. As a result, it has been found that this prediction model has the ability to estimate the change of noise map by the traffic management. In addition, the macro-traffic flow model and our conventional micro-traffic flow model were combined, and the coverage of the noise prediction model was expanded.

Noise detectives : design implications for mobile learning

In this paper, we present an account of children's interactions with a mobile technology prototype within the school context. The noise detectives trial was conducted in a school setting with the aim of better understanding the role of mobile resources as mediators within science and environmental learning activities. Over 80 children, aged between 10 and 12, completed an outdoor data-gathering activity, using a mobile learning prototype that included paper and software components. They measured and recorded noise levels in various locations throughout the school. We analysed the activity to determine how the components of the prototype were integrated into the learning activity, and to identify differences in behaviour that resulted from using these components. We present design implications that resulted from observed differences in prototype use and appropriation.

Sequential fusion of decisions from adaptive and random samples for controlled verification of errors

Fusion techniques have received considerable attention for achieving performance improvement with biometrics. While a multi-sample fusion architecture reduces false rejects, it also increases false accepts. This impact on performance also depends on the nature of subsequent attempts, i.e., random or adaptive. Expressions for error rates are presented and experimentally evaluated in this work by considering the multi-sample fusion architecture for text-dependent speaker verification using HMM based digit dependent speaker models. Analysis incorporating correlation modeling demonstrates that the use of adaptive samples improves overall fusion performance compared to randomly repeated samples. For a text dependent speaker verification system using digit strings, sequential decision fusion of seven instances with three random samples is shown to reduce the overall error of the verification system by 26% which can be further reduced by 6% for adaptive samples. This analysis novel in its treatment of random and adaptive multiple presentations within a sequential fused decision architecture, is also applicable to other biometric modalities such as finger prints and handwriting samples.

Low rank Runge-Kutta methods, symplecticity and stochastic Hamiltonian problems with additive noise

In this paper we extend the ideas of Brugnano, Iavernaro and Trigiante in their development of HBVM($s,r$) methods to construct symplectic Runge-Kutta methods for all values of $s$ and $r$ with $s\geq r$. However, these methods do not see the dramatic performance improvement that HBVMs can attain. Nevertheless, in the case of additive stochastic Hamiltonian problems an extension of these ideas, which requires the simulation of an independent Wiener process at each stage of a Runge-Kutta method, leads to methods that have very favourable properties. These ideas are illustrated by some simple numerical tests for the modified midpoint rule.

Modeling random effect and excess zeros in road traffic accident prediction

Poisson distribution has often been used for count like accident data. Negative Binomial (NB) distribution has been adopted in the count data to take care of the over-dispersion problem. However, Poisson and NB distributions are incapable of taking into account some unobserved heterogeneities due to spatial and temporal effects of accident data. To overcome this problem, Random Effect models have been developed. Again another challenge with existing traffic accident prediction models is the distribution of excess zero accident observations in some accident data. Although Zero-Inflated Poisson (ZIP) model is capable of handling the dual-state system in accident data with excess zero observations, it does not accommodate the within-location correlation and between-location correlation heterogeneities which are the basic motivations for the need of the Random Effect models. This paper proposes an effective way of fitting ZIP model with location specific random effects and for model calibration and assessment the Bayesian analysis is recommended.

Large area noise evaluation

A software tool (DRONE) has been developed to evaluate road traffic noise in a large area with the consideration of network dynamic traffic flow and the buildings. For more precise estimation of noise in urban network where vehicles are mainly in stop and go running conditions, vehicle sound power level (for acceleration/deceleration cruising and ideal vehicle) is incorporated in DRONE. The calculation performance of DRONE is increased by evaluating the noise in two steps of first estimating the unit noise database and then integrating it with traffic simulation. Details of the process from traffic simulation to contour maps are discussed in the paper and the implementation of DRONE on Tsukuba city is presented.

Document clustering evaluation : Divergence from a random baseline

Divergence from a random baseline is a technique for the evaluation of document clustering. It ensures cluster quality measures are performing work that prevents ineffective clusterings from giving high scores to clusterings that provide no useful result. These concepts are defined and analysed using intrinsic and extrinsic approaches to the evaluation of document cluster quality. This includes the classical clusters to categories approach and a novel approach that uses ad hoc information retrieval. The divergence from a random baseline approach is able to differentiate ineffective clusterings encountered in the INEX XML Mining track. It also appears to perform a normalisation similar to the Normalised Mutual Information (NMI) measure but it can be applied to any measure of cluster quality. When it is applied to the intrinsic measure of distortion as measured by RMSE, subtraction from a random baseline provides a clear optimum that is not apparent otherwise. This approach can be applied to any clustering evaluation. This paper describes its use in the context of document clustering evaluation.

Comparison of PCR, nested PCR, and random amplified polymorphic DNA PCR for detection and typing of Ureaplasma urealyticum in specimens from pregnant women

A PCR assay, using three primer pairs, was developed for the detection of Ureaplasma urealyticum, parvo biovar, mba types 1, 3, and 6, in cultured clinical specimens. The primer pairs were designed by using the polymorphic base positions within a 310- to 311-bp fragment of the 5* end and upstream control region of the mba gene. The specificity of the assay was confirmed with reference serovars 1, 3, 6, and 14 and by the amplified-fragment sizes (81 bp for mba 1, 262 bp for mba 3, and 193 bp for mba 6). A more sensitive nested PCR was also developed. This involved a first-step PCR, using the primers UMS-125 and UMA226, followed by the nested mba-type PCR described above. This nested PCR enabled the detection and typing of small numbers of U. urealyticum cells, including mixtures, directly in original clinical specimens. By using random amplified polymorphic DNA (RAPD) PCR with seven arbitrary primers, we were also able to differentiate the two biovars of U. urealyticum and to identify 13 RAPD-PCR subtypes. By applying these subtyping techniques to clinical samples collected from pregnant women, we established that (i) U. urealyticum is often a persistent colonizer of the lower genital tract from early midtrimester until the third trimester of pregnancy, (ii) mba type 6 was isolated significantly more often (P 5 0.048) from women who delivered preterm than from women who delivered at term, (iii) no particular ureaplasma subtype(s) was associated with placental infections and/or adverse pregnancy outcomes, and (iv) the ureaplasma subtypes most frequently isolated from women were the same subtypes most often isolated from infected placentas.

Abstraction as noise : enhancing the poetic

Abstraction in its resistance to evident meaning has the capacity to interrupt or at least provide tools with which to question an overly compliant reception of the information to which we are subject. It does so by highlighting a latency or potentiality inherent in materiality that points to the possibility of a critical resistance to this ceaseless flow of sound/image/data. This resistance has been remarked on in differing ways by a number of commentators such as Lyotard, in his exploration of the avant-garde and the sublime for example. This joint paper will initially map the collaborative project by Daniel Mafe and Andrew Brown, Affecting Interference which conjoins painting with digital sound and animations into a single, large scale, immersive exhibition/installation. The work acts as an interstitial point between contrasting approaches to abstraction: the visual and aural, the digital and analogue. The paper will then explore the ramifications of this through the examination of abstraction as ‘noise’, that is as that raw inassimilable materiality, within which lays the creative possibility to forge and embrace the as-yet-unthought and almost-forgotten. It does so by establishing a space for a more poetic and slower paced critical engagement for the viewing and receiving information or data. This slowing of perception through the suspension of easy recognition runs counter to our current ‘high performance’ culture, and it’s requisite demand for speedy assimilation of content, representing instead the poetic encounter with a potentiality or latency inherent in the nameless particularity of that which is.