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  • Public defence: 2019-03-08 13:15 Gamma, Västerås
    Weishaupt, Hrafn Holger
    Mälardalen University, School of Education, Culture and Communication, Educational Sciences and Mathematics.
    Graph theory based approaches for gene prioritization in biological networks: Application to cancer gene detection in medulloblastoma2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Networks provide an intuitive and highly adaptable means to model relationships between objects. When translated to mathematical graphs, they become further amenable to a plethora of mathematical operations that allow a detailed study of the underlying relational data. Thus, it is not surprising that networks have evolved to a predominant method for analyzing such data in a vast variety of research fields. However, with increasing complexity of the studied problems, application of network modeling also becomes more challenging. Specifically, given a process to be studied, (i) which interactions are important and how can they be modeled, (ii) how can relationships be inferred from complex and potentially noisy data, and (iii) which methods should be used to test hypotheses or answer the relevant questions? This thesis explores the concept and challenges of network analysis in the context of a well-defined application area, i.e. the prediction of cancer genes from biological networks, with an application to medulloblastoma research.

    Medulloblastoma represents the most common malignant brain tumor in children. Currently about 70% of treated patients survive, but they often suffer from permanent cognitive sequelae. Medulloblastoma has previously been shown to harbor at least four distinct molecular subgroups. Related studies have also greatly advanced our understanding of the genetic aberrations associated with MB subgroups. However, to translate such findings to novel and improved therapy options, further insights are required into how the dysregulated genes interact with the rest of the cellular system, how such a cross-talk can drive tumor development, and how the arising tumorigenic processes can be targeted by drugs. Establishing such understanding requires investigations that can address biological processes at a more system-wide level, a task that can be approached through the study of cellular systems as mathematical networks of molecular interactions.

    This thesis discusses the identification of cancer genes from a network perspective, where specific focus is placed on one particular type of network, i.e. so called gene regulatory networks that model relationships between genes at the expression level. The thesis outlines the bridge between biological and mathematical network concepts. Specifically, the computational challenge of inferring such networks from molecular data is presented. Mathematical approaches for analyzing these networks are outlined and it is explored how such methods might be affected by network inference. Further focus is placed on dealing with the challenges of establishing a suitable gene expression dataset for network inference in MB. Finally, the thesis is concluded with an application of various network approaches in a hypothesis-driven study in MB, in which various novel candidate genes were prioritized.  

  • Public defence: 2019-03-19 09:30 Gamma, Västerås
    Du, Jiaying
    Mälardalen University, School of Innovation, Design and Engineering, Embedded Systems. -.
    Real-time signal processing in MEMS sensor-based motion analysis systems2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This PhD thesis focuses on real-time signal processing for hardware-limited micro-electro-mechanical system (MEMS) sensor-based human motion analysis systems. The aim of the thesis is to improve the signal quality of MEMS gyroscopes and accelerometers by minimizing the effects of signal errors, considering the hardware limitations and the users' perception.

    MEMS sensors such as MEMS gyroscopes and MEMS accelerometers are important components in motion analysis systems. They are known for their small size, light weight, low power consumption, low cost, and high sensitivity. This makes them suitable for wearable systems for measuring body movements. The data can further be used as input for advanced human motion analyses. However, MEMS sensors are usually sensitive to environmental disturbances such as shock, vibration, and temperature change. A large portion of the MEMS sensor signals actually originate from error sources such as noise, offset, null drift and temperature drift, as well as integration drift. Signal processing is regarded as the major key solution to reduce these errors. For real-time signal processing, the algorithms need to be executed within a certain specified time limit. Two crucial factors have to be considered when designing real-time signal processing algorithms for wearable embedded sensor systems. One is the hardware limitations leading to a limited calculation capacity, and the other is the user perception of the delay caused by the signal processing.

    Within this thesis, a systematic review of different signal error reduction algorithms for MEMS gyroscope-based motion analysis systems for human motion analysis is presented. The users’ perceptions of the delay when using different computer input devices were investigated. 50 ms was found as an acceptable delay for the signal processing execution in a real-time motion analysis system. Real-time algorithms for noise reduction, offset/drift estimation and reduction, improvement of position accuracy and system stability considering the above mentioned requirements, are presented in this thesis. The algorithms include a simplified high-pass filter and low-pass filter, a LMS algorithm, a Kalman filter, a WFLC algorithm, two simple novel algorithms (a TWD method and a velocity drift estimation method), and a novel combination method KWT.  Kalman filtering was found to be efficient to reduce the problem of temperature drift and the WFLC algorithm was found the most suitable method to reduce human physiological tremor and electrical noise. The TWD method resulted in a signal level around zero without interrupting the continuous movement signal. The combination method improved the static stability and the position accuracy considerably.  The computational time for the execution of the algorithms were all perceived as acceptable by users and kept within the specified time limit for real-time performance.  Implementations and experiments showed that these algorithms are feasible for establishing high signal quality and good system performance in previously developed systems, and also have the potential to be used in similar systems.

    The full text will be freely available from 2019-02-26 08:00