Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

Ensemble fuzzy belief intrusion detection design

With the rapid growth of the Internet, computer attacks are increasing at a fast pace and can easily cause millions of dollar in damage to an organization. Detecting these attacks is an important issue of computer security. There are many types of attacks and they fall into four main categories, Denial of Service (DoS) attacks, Probe, User to Root (U2R) attacks, and Remote to Local (R2L) attacks. Within these categories, DoS and Probe attacks continuously show up with greater frequency in a short period of time when they attack systems. They are different from the normal traffic data and can be easily separated from normal activities. On the contrary, U2R and R2L attacks are embedded in the data portions of the packets and normally involve only a single connection. It becomes difficult to achieve satisfactory detection accuracy for detecting these two attacks. Therefore, we focus on studying the ambiguity problem between normal activities and U2R/R2L attacks. The goal is to build a detection system that can accurately and quickly detect these two attacks. In this dissertation, we design a two-phase intrusion detection approach. In the first phase, a correlation-based feature selection algorithm is proposed to advance the speed of detection. Features with poor prediction ability for the signatures of attacks and features inter-correlated with one or more other features are considered redundant. Such features are removed and only indispensable information about the original feature space remains. In the second phase, we develop an ensemble intrusion detection system to achieve accurate detection performance. The proposed method includes multiple feature selecting intrusion detectors and a data mining intrusion detector. The former ones consist of a set of detectors, and each of them uses a fuzzy clustering technique and belief theory to solve the ambiguity problem. The latter one applies data mining technique to automatically extract computer users’ normal behavior from training network traffic data. The final decision is a combination of the outputs of feature selecting and data mining detectors. The experimental results indicate that our ensemble approach not only significantly reduces the detection time but also effectively detect U2R and R2L attacks that contain degrees of ambiguous information.

An epistemic event -based correlation scheme for pervasive network management

Computer networks produce tremendous amounts of event-based data that can be collected and managed to support an increasing number of new classes of pervasive applications. Examples of such applications are network monitoring and crisis management. Although the problem of distributed event-based management has been addressed in the non-pervasive settings such as the Internet, the domain of pervasive networks has its own characteristics that make these results non-applicable. Many of these applications are based on time-series data that possess the form of time-ordered series of events. Such applications also embody the need to handle large volumes of unexpected events, often modified on-the-fly, containing conflicting information, and dealing with rapidly changing contexts while producing results with low-latency. Correlating events across contextual dimensions holds the key to expanding the capabilities and improving the performance of these applications. This dissertation addresses this critical challenge. It establishes an effective scheme for complex-event semantic correlation. The scheme examines epistemic uncertainty in computer networks by fusing event synchronization concepts with belief theory. Because of the distributed nature of the event detection, time-delays are considered. Events are no longer instantaneous, but duration is associated with them. Existing algorithms for synchronizing time are split into two classes, one of which is asserted to provide a faster means for converging time and hence better suited for pervasive network management. Besides the temporal dimension, the scheme considers imprecision and uncertainty when an event is detected. A belief value is therefore associated with the semantics and the detection of composite events. This belief value is generated by a consensus among participating entities in a computer network. The scheme taps into in-network processing capabilities of pervasive computer networks and can withstand missing or conflicting information gathered from multiple participating entities. Thus, this dissertation advances knowledge in the field of network management by facilitating the full utilization of characteristics offered by pervasive, distributed and wireless technologies in contemporary and future computer networks.

Ensemble Fuzzy Belief Intrusion Detection Design

With the rapid growth of the Internet, computer attacks are increasing at a fast pace and can easily cause millions of dollar in damage to an organization. Detecting these attacks is an important issue of computer security. There are many types of attacks and they fall into four main categories, Denial of Service (DoS) attacks, Probe, User to Root (U2R) attacks, and Remote to Local (R2L) attacks. Within these categories, DoS and Probe attacks continuously show up with greater frequency in a short period of time when they attack systems. They are different from the normal traffic data and can be easily separated from normal activities. On the contrary, U2R and R2L attacks are embedded in the data portions of the packets and normally involve only a single connection. It becomes difficult to achieve satisfactory detection accuracy for detecting these two attacks. Therefore, we focus on studying the ambiguity problem between normal activities and U2R/R2L attacks. The goal is to build a detection system that can accurately and quickly detect these two attacks. In this dissertation, we design a two-phase intrusion detection approach. In the first phase, a correlation-based feature selection algorithm is proposed to advance the speed of detection. Features with poor prediction ability for the signatures of attacks and features inter-correlated with one or more other features are considered redundant. Such features are removed and only indispensable information about the original feature space remains. In the second phase, we develop an ensemble intrusion detection system to achieve accurate detection performance. The proposed method includes multiple feature selecting intrusion detectors and a data mining intrusion detector. The former ones consist of a set of detectors, and each of them uses a fuzzy clustering technique and belief theory to solve the ambiguity problem. The latter one applies data mining technique to automatically extract computer users’ normal behavior from training network traffic data. The final decision is a combination of the outputs of feature selecting and data mining detectors. The experimental results indicate that our ensemble approach not only significantly reduces the detection time but also effectively detect U2R and R2L attacks that contain degrees of ambiguous information.

An Epistemic Event-based Correlation Scheme for Pervasive Network Management

Computer networks produce tremendous amounts of event-based data that can be collected and managed to support an increasing number of new classes of pervasive applications. Examples of such applications are network monitoring and crisis management. Although the problem of distributed event-based management has been addressed in the non-pervasive settings such as the Internet, the domain of pervasive networks has its own characteristics that make these results non-applicable. Many of these applications are based on time-series data that possess the form of time-ordered series of events. Such applications also embody the need to handle large volumes of unexpected events, often modified on-the-fly, containing conflicting information, and dealing with rapidly changing contexts while producing results with low-latency. Correlating events across contextual dimensions holds the key to expanding the capabilities and improving the performance of these applications. This dissertation addresses this critical challenge. It establishes an effective scheme for complex-event semantic correlation. The scheme examines epistemic uncertainty in computer networks by fusing event synchronization concepts with belief theory. Because of the distributed nature of the event detection, time-delays are considered. Events are no longer instantaneous, but duration is associated with them. Existing algorithms for synchronizing time are split into two classes, one of which is asserted to provide a faster means for converging time and hence better suited for pervasive network management. Besides the temporal dimension, the scheme considers imprecision and uncertainty when an event is detected. A belief value is therefore associated with the semantics and the detection of composite events. This belief value is generated by a consensus among participating entities in a computer network. The scheme taps into in-network processing capabilities of pervasive computer networks and can withstand missing or conflicting information gathered from multiple participating entities. Thus, this dissertation advances knowledge in the field of network management by facilitating the full utilization of characteristics offered by pervasive, distributed and wireless technologies in contemporary and future computer networks.