IDENTIFICATION OF GENES CONTROLLING BIOLOGICAL PROCESSES AND PATHWAYS THROUGH STATISTICAL ANALYSIS AND NETWORK RECONSTRUCTION

The developmental processes and functions of an organism are controlled by the genes and the proteins that are derived from these genes. The identification of key genes and the reconstruction of gene networks can provide a model to help us understand the regulatory mechanisms for the initiation and progression of biological processes or functional abnormalities (e.g. diseases) in living organisms. In this dissertation, I have developed statistical methods to identify the genes and transcription factors (TFs) involved in biological processes, constructed their regulatory networks, and also evaluated some existing association methods to find robust methods for coexpression analyses. Two kinds of data sets were used for this work: genotype data and gene expression microarray data. On the basis of these data sets, this dissertation has two major parts, together forming six chapters. The first part deals with developing association methods for rare variants using genotype data (chapter 4 and 5). The second part deals with developing and/or evaluating statistical methods to identify genes and TFs involved in biological processes, and construction of their regulatory networks using gene expression data (chapter 2, 3, and 6). For the first part, I have developed two methods to find the groupwise association of rare variants with given diseases or traits. The first method is based on kernel machine learning and can be applied to both quantitative as well as qualitative traits. Simulation results showed that the proposed method has improved power over the existing weighted sum method (WS) in most settings. The second method uses multiple phenotypes to select a few top significant genes. It then finds the association of each gene with each phenotype while controlling the population stratification by adjusting the data for ancestry using principal components. This method was applied to GAW 17 data and was able to find several disease risk genes. For the second part, I have worked on three problems. First problem involved evaluation of eight gene association methods. A very comprehensive comparison of these methods with further analysis clearly demonstrates the distinct and common performance of these eight gene association methods. For the second problem, an algorithm named the bottom-up graphical Gaussian model was developed to identify the TFs that regulate pathway genes and reconstruct their hierarchical regulatory networks. This algorithm has produced very significant results and it is the first report to produce such hierarchical networks for these pathways. The third problem dealt with developing another algorithm called the top-down graphical Gaussian model that identifies the network governed by a specific TF. The network produced by the algorithm is proven to be of very high accuracy.

DESIGN AND IMPLEMENTATION OF HOME USE PORTABLE SMART ELECTRONICS

The widespread of low cost embedded electronics makes it easier to implement the smart devices that can understand either the environment or the user behaviors. The main object of this project is to design and implement home use portable smart electronics, including the portable monitoring device for home and office security and the portable 3D mouse for convenient use. Both devices in this project use the MPU6050 which contains a 3 axis accelerometer and a 3 axis gyroscope to sense the inertial motion of the door or the human hands movement. For the portable monitoring device for home and office security, MPU6050 is used to sense the door (either home front door or cabinet door) movement through the gyroscope, and Raspberry Pi is then used to process the data it receives from MPU6050, if the data value exceeds the preset threshold, Raspberry Pi would control the USB Webcam to take a picture and then send out an alert email with the picture to the user. The advantage of this device is that it is a small size portable stand-alone device with its own power source, it is easy to implement, really cheap for residential use, and energy efficient with instantaneous alert. For the 3D mouse, the MPU6050 would use both the accelerometer and gyroscope to sense user hands movement, the data are processed by MSP430G2553 through a digital smooth filter and a complementary filter, and then the filtered data will pass to the personal computer through the serial COM port. By applying the cursor movement equation in the PC driver, this device can work great as a mouse with acceptable accuracy. Compared to the normal optical mouse we are using, this mouse does not need any working surface, with the use of the smooth and complementary filter, it has certain accuracy for normal use, and it is easy to be extended to a portable mouse as small as a finger ring.

Robustness of speckle imaging techniques applied to horizontal imaging scenarios

Atmospheric turbulence near the ground severely limits the quality of imagery acquired over long horizontal paths. In defense, surveillance, and border security applications, there is interest in deploying man-portable, embedded systems incorporating image reconstruction methods to compensate turbulence effects. While many image reconstruction methods have been proposed, their suitability for use in man-portable embedded systems is uncertain. To be effective, these systems must operate over significant variations in turbulence conditions while subject to other variations due to operation by novice users. Systems that meet these requirements and are otherwise designed to be immune to the factors that cause variation in performance are considered robust. In addition robustness in design, the portable nature of these systems implies a preference for systems with a minimum level of computational complexity. Speckle imaging methods have recently been proposed as being well suited for use in man-portable horizontal imagers. In this work, the robustness of speckle imaging methods is established by identifying a subset of design parameters that provide immunity to the expected variations in operating conditions while minimizing the computation time necessary for image recovery. Design parameters are selected by parametric evaluation of system performance as factors external to the system are varied. The precise control necessary for such an evaluation is made possible using image sets of turbulence degraded imagery developed using a novel technique for simulating anisoplanatic image formation over long horizontal paths. System performance is statistically evaluated over multiple reconstruction using the Mean Squared Error (MSE) to evaluate reconstruction quality. In addition to more general design parameters, the relative performance the bispectrum and the Knox-Thompson phase recovery methods is also compared. As an outcome of this work it can be concluded that speckle-imaging techniques are robust to the variation in turbulence conditions and user controlled parameters expected when operating during the day over long horizontal paths. Speckle imaging systems that incorporate 15 or more image frames and 4 estimates of the object phase per reconstruction provide up to 45% reduction in MSE and 68% reduction in the deviation. In addition, Knox-Thompson phase recover method is shown to produce images in half the time required by the bispectrum. The quality of images reconstructed using Knox-Thompson and bispectrum methods are also found to be nearly identical. Finally, it is shown that certain blind image quality metrics can be used in place of the MSE to evaluate quality in field scenarios. Using blind metrics rather depending on user estimates allows for reconstruction quality that differs from the minimum MSE by as little as 1%, significantly reducing the deviation in performance due to user action.

Analysis of spring break-up and its effects on a biomass feedstock supply chain in northern Michigan

Demand for bio-fuels is expected to increase, due to rising prices of fossil fuels and concerns over greenhouse gas emissions and energy security. The overall cost of biomass energy generation is primarily related to biomass harvesting activity, transportation, and storage. With a commercial-scale cellulosic ethanol processing facility in Kinross Township of Chippewa County, Michigan about to be built, models including a simulation model and an optimization model have been developed to provide decision support for the facility. Both models track cost, emissions and energy consumption. While the optimization model provides guidance for a long-term strategic plan, the simulation model aims to present detailed output for specified operational scenarios over an annual period. Most importantly, the simulation model considers the uncertainty of spring break-up timing, i.e., seasonal road restrictions. Spring break-up timing is important because it will impact the feasibility of harvesting activity and the time duration of transportation restrictions, which significantly changes the availability of feedstock for the processing facility. This thesis focuses on the statistical model of spring break-up used in the simulation model. Spring break-up timing depends on various factors, including temperature, road conditions and soil type, as well as individual decision making processes at the county level. The spring break-up model, based on the historical spring break-up data from 27 counties over the period of 2002-2010, starts by specifying the probability distribution of a particular county’s spring break-up start day and end day, and then relates the spring break-up timing of the other counties in the harvesting zone to the first county. In order to estimate the dependence relationship between counties, regression analyses, including standard linear regression and reduced major axis regression, are conducted. Using realizations (scenarios) of spring break-up generated by the statistical spring breakup model, the simulation model is able to probabilistically evaluate different harvesting and transportation plans to help the bio-fuel facility select the most effective strategy. For early spring break-up, which usually indicates a longer than average break-up period, more log storage is required, total cost increases, and the probability of plant closure increases. The risk of plant closure may be partially offset through increased use of rail transportation, which is not subject to spring break-up restrictions. However, rail availability and rail yard storage may then become limiting factors in the supply chain. Rail use will impact total cost, energy consumption, system-wide CO2 emissions, and the reliability of providing feedstock to the bio-fuel processing facility.

Balancing wildlife and bioenergy values on private forestlands in the eastern Upper Peninsula of Michigan

There is interest in developing a reliable, sustainable, domestic U.S. biofuels industry. A domestic biofuels industry has the potential to provide economic, environmental, and national security benefits on a local, regional, national, and global level. The Mascoma Corporation plans to develop a cellulosic ethanol facility in Michigan’s eastern Upper Peninsula. The primary feedstock of the plant site would be trees sourced within a 150 mile supply radius. In the eastern Upper Peninsula, this radius encompasses Alger, Chippewa, Delta, Luce, Mackinac, and Schoolcraft counties. In these six counties there are 1,320,500 acres of NIPF (non-industrial private forestlands). These acres account for 40% of the total timberland in these six counties. Thus it is likely that in order for the successful implementation of a cellulosic ethanol facility the support of local NIPF owners will be necessary. This thesis presents research on how eastern Upper Peninsula forest landowners think about and manage their land. It is based on 48 in-depth interviews with these landowners. The goal was to determine how landowner values and beliefs, on a variety of issues including wildlife management, land management, biofuels development, and climate change, are expressed through both their current management decisions, and possibly their future land management decisions. Some of the values articulated by the landowners in this study included biodiversity protection, conservation of healthy game populations, and the production of high-value timber. Understanding the values and beliefs of landowners in the eastern Upper Peninsula of Michigan is critical for successfully developing a sustainable regional woody bioenergy.