Novel Computationally Intelligent Machine Learning Algorithms for Data Mining and Knowledge Discovery

This thesis addresses three major issues in data mining regarding feature subset selection in large dimensionality domains, plausible reconstruction of incomplete data in cross-sectional applications, and forecasting univariate time series. For the automated selection of an optimal subset of features in real time, we present an improved hybrid algorithm: SAGA. SAGA combines the ability to avoid being trapped in local minima of Simulated Annealing with the very high convergence rate of the crossover operator of Genetic Algorithms, the strong local search ability of greedy algorithms and the high computational efficiency of generalized regression neural networks (GRNN). For imputing missing values and forecasting univariate time series, we propose a homogeneous neural network ensemble. The proposed ensemble consists of a committee of Generalized Regression Neural Networks (GRNNs) trained on different subsets of features generated by SAGA and the predictions of base classifiers are combined by a fusion rule. This approach makes it possible to discover all important interrelations between the values of the target variable and the input features. The proposed ensemble scheme has two innovative features which make it stand out amongst ensemble learning algorithms: (1) the ensemble makeup is optimized automatically by SAGA; and (2) GRNN is used for both base classifiers and the top level combiner classifier. Because of GRNN, the proposed ensemble is a dynamic weighting scheme. This is in contrast to the existing ensemble approaches which belong to the simple voting and static weighting strategy. The basic idea of the dynamic weighting procedure is to give a higher reliability weight to those scenarios that are similar to the new ones. The simulation results demonstrate the validity of the proposed ensemble model

Animal genomics and infectious disease resistance in poultry

Avian pathogens are responsible for major costs to society, both in terms of huge economic losses to the poultry industry and their implications for human health. The health and welfare of millions of birds is under continued threat from many infectious diseases, some of which are increasing in virulence and thus becoming harder to control, such as Marek's disease virus and avian influenza viruses. The current era in animal genomics has seen huge developments in both technologies and resources, which means that researchers have never been in a better position to investigate the genetics of disease resistance and determine the underlying genes/mutations which make birds susceptible or resistant to infection. Avian genomics has reached a point where the biological mechanisms of infectious diseases can be investigated and understood in poultry and other avian species. Knowledge of genes conferring disease resistance can be used in selective breeding programmes or to develop vaccines which help to control the effects of these pathogens, which have such a major impact on birds and humans alike

The Involvement of Caspases in the Process of Nuclear Removal During Lens Fiber Cell Differentiation

The terminal differentiation of lens fiber cells involves elimination of their organelles, which must occur while still maintaining their functionality throughout a lifetime. Removal of non-nuclear organelles is accomplished through induction of autophagy following the spatiotemporal suppression of the PI3K/Akt signaling axis. However, blocking this pathway is not alone sufficient to induce removal of fiber cell nuclei. While the final steps in fiber cell nuclear elimination are highlighted by the appearance of TUNEL-positive nuclei, which are associated with activation of the lens-specific DNaseIIβ, there are many steps in the process that precede the appearance of double stranded DNA breaks. We showed that this carefully regulated process, including the early changes in nuclear morphology resulting in nuclear condensation, cleavage of lamin B, and labeling by pH2AX, is reminiscent of the apoptotic process associated with caspase activation. Multiple caspases are known to be expressed and activated during lens cell differentiation. In this study, we investigated the link between two caspase downstream targets associated with apoptosis, ICAD, whose cleavage by caspase-3 leads to activation of CAD, a DNase that can create both single- and double-stranded DNA cleavages, and lamin B, a primary component of the nuclear lamina. We discovered that the specific inhibition of caspase-3 activation prevents both lamin B and DNA cleavage. Inhibiting caspase-3 did not prevent nuclear condensation or removal of the nuclear membrane. In contrast, a pan-caspase inhibitor effectively suppressed condensation of fiber cell nuclei during differentiation. These studies provide evidence that caspases play an important role in the process of removing fiber cell nuclei during lens differentiation

Examining pi3K-Signaling-Dependent Regulation of Lens Organelle Free Zone Formation via Immunolocalization and Immunoblotting in Chick Embryos

The elimination of lens organelles during development, required for mature lens function, is an autophagy-dependent mechanism induced through suppression of PI3K signaling. Here, we present a protocol for investigating the signaling pathways responsible for induction of the formation of this lens organelle free zone. We describe steps for preparation of lens organ culture and use of signaling pathway inhibitors. We then detail procedures for analyzing their impact using both confocal microscopy imaging of immunolabeled lens cryosections and immunoblot approaches. For complete details on the use and execution of this protocol, please refer to Gheyas et al. (2022)

Optimal Meshing Degree Performance Analysis in a mmWave FWA 5G Network Deployment

Fifth-generation technologies have reached a stage where it is now feasible to consider deployments that extend beyond traditional public networks. Central to this process is the application of Fixed Wireless Access (FWA) in 5G Non-public Networks (NPNs) that can utilise a novel combination of radio technologies to deploy an infrastructure on top of 5G NR or entirely from scratch. However, the use of FWA backhaul faces many challenges in relation to the trade-offs for reduced costs and a relatively simple deployment. Specifically, the use of meshed deployments is critical as it provides resilience against a temporary loss of connectivity due to link errors. In this paper, we examine the use of meshing in a FWA backhaul to determine if an optimal trade-off exists between the deployment of more nodes/links to provide multiple paths to the nearest Point of Presence (POP) and the performance of the network. Using a real 5G NPN deployment as a basis, we have conducted a simulated analysis of increasing network densities to determine the optimal configuration. Our results show a clear advantage for meshing in general, but there is also a performance trade-off to consider between overall network throughput and stability

Heritability estimation of silver carp (Hypophthalmichthys molitrix) harvest traits using microsatellite based parentage assignment

Silver carp accounts for the largest biomass production of any finfish aquaculture species in the world. In spite of its great importance as an aquacultural species, very little is known about the genetic parameters of its commercially important traits. As an initial step towards developing a selective breeding programme, heritability of harvest weight and length was estimated for a silver carp stock maintained in the NFRDMP (North West Fisheries Resource Development and Management Project) hatchery in Bangladesh. Three sets of partial factorial matings were performed (12 sires and 12 dams in each set) to produce full and half-sib families for this study. Offspring from all families produced in a set were reared communally for six months and then weighed and measured upon harvesting. Ten silver carp microsatellite markers were included in two multiplex PCR systems and were used to assign parentage to the individuals. Out of 331 offspring, 96.3% could be assigned to a single family. Statistical analyses to partition the variance components for weight and length data were carried out by the REML (Restricted Maximum Likelihood) method. Heritability for harvest weight was estimated to be 0.67 (confidence interval: 0.42-0.93) and for harvest length 0.51 (confidence interval: 0.29-0.78). Despite the limited sample size, the moderate to high heritability estimates suggest that this population should respond rapidly to selective breeding for increased harvest size. In addition to this first report of quantitative genetic parameters in silver carp, this paper also describes two novel multiplexes of silver carp microsatellite markers for parentage assignment and discusses the effects of the partial factorial mating design in maintaining effective population size in this species

Contagion in cybersecurity attacks

Systems security is essential for the efficient operation of all organizations. Indeed, most large firms employ a designated 'Chief Information Security Officer' to coordinate the operational aspects of the organization’s information security. Part of this role is in planning investment responses to information security threats against the firm's corporate network infrastructure. To this end, we develop and estimate a vector equation system of threats to 10 important IP services, using industry standard SANS data on threats to various components of a firm's information system over the period January 2003 – February 2011. Our results reveal strong evidence of contagion between such attacks, with attacks on ssh and Secure Web Server indicating increased attack activity on other ports. Security managers who ignore such contagious inter-relationships may underestimate the underlying risk to their systems' defence of security attributes, such as sensitivity and criticality, and thus delay appropriate information security investments

Suppression of PI3K signaling is linked to autophagy activation and the spatiotemporal induction of the lens organelle free zone

The terminal steps of lens cell differentiation require elimination of all organelles to create a central Organelle Free Zone (OFZ) that is required for lens function of focusing images on the retina. Previous studies show that the spatiotemporal elimination of these organelles during development is autophagy-dependent. We now show that the inhibition of PI3K signaling in lens organ culture results in the premature induction of autophagy within 24 h, including a significant increase in LAMP1+ lysosomes, and the removal of lens organelles from the center of the lens. Specific inhibition of just the PI3K/Akt signaling axis was directly linked to the elimination of mitochondria and ER, while pan-PI3K inhibitors that block all PI3K downstream signaling removed all organelles, including nuclei. Therefore, blocking the PI3K/Akt pathway was alone insufficient to remove nuclei. RNAseq analysis revealed increased mRNA levels of the endogenous inhibitor of PI3K activation, PIK3IP1, in differentiating lens fiber cells preceding the induction of OFZ formation. Co-immunoprecipitation confirmed that PIK3IP1 associates with multiple PI3K p110 isoforms just prior to formation of the OFZ, providing a likely endogenous mechanism for blocking all PI3K signaling and activating the autophagy pathway required to form the OFZ during lens development

Reviving rare chicken breeds using genetically engineered sterility in surrogate host birds

In macrolecithal species, cryopreservation of the oocyte and zygote is not possible due to the large size and quantity of lipid deposited within the egg. For birds, this signifies that cryopreserving and regenerating a species from frozen cellular material are currently technically unfeasible. Diploid primordial germ cells (PGCs) are a potential means to freeze down the entire genome and reconstitute an avian species from frozen material. Here, we examine the use of genetically engineered (GE) sterile female layer chicken as surrogate hosts for the transplantation of cryopreserved avian PGCs from rare heritage breeds of chicken. We first amplified PGC numbers in culture before cryopreservation and subsequent transplantation into host GE embryos. We found that all hatched offspring from the chimera GE hens were derived from the donor rare heritage breed broiler PGCs, and using cryopreserved semen, we were able to produce pure offspring. Measurement of the mutation rate of PGCs in culture revealed that 2.7 × 10-10 de novo single-nucleotide variants (SNVs) were generated per cell division, which is comparable with other stem cell lineages. We also found that endogenous avian leukosis virus (ALV) retroviral insertions were not mobilized during in vitro propagation. Taken together, these results show that mutation rates are no higher than normal stem cells, essential if we are to conserve avian breeds. Thus, GE sterile avian surrogate hosts provide a viable platform to conserve and regenerate avian species using cryopreserved PGCs

Analysis of the progeny of sibling matings reveals regulatory variation impacting the transcriptome of immune cells in commercial chickens

There is increasing recognition that the underlying genetic variation contributing to complex traits influences transcriptional regulation and can be detected at a population level as expression quantitative trait loci. At the level of an individual, allelic variation in transcriptional regulation of individual genes can be detected by measuring allele-specific expression in RNAseq data. We reasoned that extreme variants in gene expression could be identified by analysis of inbred progeny with shared grandparents. Commercial chickens have been intensively selected for production traits. Selection is associated with large blocks of linkage disequilibrium with considerable potential for co-selection of closely linked “hitch-hiker alleles” affecting traits unrelated to the feature being selected, such as immune function, with potential impact on the productivity and welfare of the animals. To test this hypothesis that there is extreme allelic variation in immune-associated genes we sequenced a founder population of commercial broiler and layer birds. These birds clearly segregated genetically based upon breed type. Each genome contained numerous candidate null mutations, protein-coding variants predicted to be deleterious and extensive non-coding polymorphism. We mated selected broiler-layer pairs then generated cohorts of F2 birds by sibling mating of the F1 generation. Despite the predicted prevalence of deleterious coding variation in the genomic sequence of the founders, clear detrimental impacts of inbreeding on survival and post-hatch development were detected in only one F2 sibship of 15. There was no effect on circulating leukocyte populations in hatchlings. In selected F2 sibships we performed RNAseq analysis of the spleen and isolated bone marrow-derived macrophages (with and without lipopolysaccharide stimulation). The results confirm the predicted emergence of very large differences in expression of individual genes and sets of genes. Network analysis of the results identified clusters of co-expressed genes that vary between individuals and suggested the existence of trans-acting variation in the expression in macrophages of the interferon response factor family that distinguishes the parental broiler and layer birds and influences the global response to lipopolysaccharide. This study shows that the impact of inbreeding on immune cell gene expression can be substantial at the transcriptional level, and potentially opens a route to accelerate selection using specific alleles known to be associated with desirable expression levels