<div> <div> <div> <p>Understanding protein-protein interactions (PPIs) in a cell is essential for learning protein functions, pathways, and mechanisms of diseases. This dissertation introduces the computational method to predict PPIs. In the first chapter, the history of identifying protein interactions and some experimental methods are introduced. Because interacting proteins share similar functions, protein function similarity can be used as a feature to predict PPIs. NaviGO server is developed for biologists and bioinformaticians to visualize the gene ontology relationship and quantify their similarity scores. Furthermore, the computational features used to predict PPIs are summarized. This will help researchers from the computational field to understand the rationale of extracting biological features and also benefit the researcher with a biology background to understand the computational work. After understanding various computational features, the computational prediction method to identify large-scale PPIs was developed and applied to Arabidopsis, maize, and soybean in a whole-genomic scale. Novel predicted PPIs were provided and were grouped based on prediction confidence level, which can be used as a testable hypothesis to guide biologists’ experiments. Since affinity chromatography combined with mass spectrometry technique introduces high false PPIs, the computational method was combined with mass spectrometry data to aid the identification of high confident PPIs in large-scale. Lastly, some remaining challenges of the computational PPI prediction methods and future works are discussed. </p> </div> </div> </div>

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The ability to rapidly assess the condition of a structure in a manner which enables the accurate prediction of its remaining capacity has long been viewed as a crucial step in allowing communities to make safe and efficient use of their public infrastructure. This objective has become even more relevant in recent years as both the interdependency and state of deterioration in infrastructure systems throughout the world have increased. Current practice for structural condition assessment emphasizes visual inspection, in which trained professionals will routinely survey a structure to estimate its remaining capacity. Though these methods have the ability to monitor gross structural changes, their ability to rapidly and cost-effectively assess the detailed condition of the structure with respect to its future behavior is limited.<div>Vibration-based monitoring techniques offer a promising alternative to this approach. As opposed to visually observing the surface of the structure, these methods judge its condition and infer its future performance by generating and updating models calibrated to its dynamic behavior. Bayesian inference approaches are particularly well suited to this model updating problem as they are able to identify the structure using sparse observations while simultaneously assessing the uncertainty in the identified parameters. However, a lack of consensus on efficient methods for their implementation to full-scale structural systems has led to a diverse set of Bayesian approaches, from which no clear method can be selected for full-scale implementation. The objective of this work is therefore to assess and enhance those techniques currently used for structural identification and make strides toward developing unified strategies for robustly implementing them on full-scale structures. This is accomplished by addressing several key research questions regarding the ability of these methods to overcome issues in identifiability, sensitivity to uncertain experimental conditions, and scalability. These questions are investigated by applying novel adaptations of several prominent Bayesian identification strategies to small-scale experimental systems equipped with nonlinear devices. Through these illustrative examples I explore the robustness and practicality of these algorithms, while also considering their extensibility to higher-dimensional systems. Addressing these core concerns underlying full-scale structural identification will enable the practical application of Bayesian inference techniques and thereby enhance the ability of communities to detect and respond to the condition of their infrastructure.<br></div>

McMaster University MASTER OF PUBLIC HEALTH (2020) Hamilton, Ontario (Health Research Methods, Evidence, and Impact) TITLE: Applying Machine Learning to Determine Nutrients Predictive of Cardiovascular Disease Using Canadian Linked Population-Based Data AUTHOR: Jason D. Morgenstern, B.Sc. (University of Guelph), M.D. (Western University) SUPERVISOR: Professor L.N. Anderson, NUMBER OF PAGES: xv, 121 / The use of big data and machine learning may help to address some challenges in nutritional epidemiology. The first objective of this thesis was to explore the use of machine learning prediction models in a hypothesis-generating approach to evaluate how detailed dietary features contribute to CVD risk prediction. The second objective was to assess the predictive performance of the models. A population-based retrospective cohort study was conducted using linked Canadian data from 2004 – 2018. Study participants were adults age 20 and older (n=12 130 ) who completed the 2004 Canadian Community Health Survey, Cycle 2.2, Nutrition (CCHS 2.2). Statistics Canada has linked the CCHS 2.2 data to the Discharge Abstracts Database and the Canadian Vital Statistics Death database, which were used to determine cardiovascular outcomes (stroke or ischemic heart disease events or deaths). Conditional inference forests were used to develop models. Then, permutation feature importance (PFI) and accumulated local effects (ALEs) were calculated to explore contributions of nutrients to predicted disease. Supplement-use (median PFI (M)=4.09 x 10-4, IQR=8.25 x 10-7 – 1.11 x 10-3) and caffeine (M=2.79 x 10-4, IQR= -9.11 x 10-5 – 5.86 x 10-4) had the highest median PFIs for nutrition-related features. Supplement-use was associated with decreased predicted risk of CVD (accumulated local effects range (ALER)= -3.02 x 10-4 – 2.76 x 10-4) and caffeine was associated with increased predicted risk (ALER= -9.96 x 10-4 – 0.035). The best-performing model had a logarithmic loss of 0.248. Overall, many non-linear relationships were observed, including threshold, j-shaped, and u-shaped. The results of this exploratory study suggest that applying machine learning to the nutritional epidemiology of CVD, particularly using big datasets, may help elucidate risks and improve predictive models. Given the limited application thus far, work such as this could lead to improvements in public health recommendations and policy related to dietary behaviours. / Thesis / Master of Public Health (MPH) / This work explores the potential for machine learning to improve the study of diet and disease. In chapter 2, opportunities are identified for big data to make diet easier to measure. Also, we highlight how machine learning could find new, complex relationships between diet and disease. In chapter 3, we apply a machine learning algorithm, called conditional inference forests, to a unique Canadian dataset to predict whether people developed strokes or heart attacks. This dataset included responses to a health survey conducted in 2004, where participants’ responses have been linked to administrative databases that record when people go to hospital or die up until 2017. Using these techniques, we identified aspects of nutrition that predicted disease, including caffeine, alcohol, and supplement-use. This work suggests that machine learning may be helpful in our attempts to understand the relationships between diet and health.

Tropical forests provide important habitat for a tremendous diversity of plant and animal species. However, limitations in measuring and monitoring the structure and function of tropical forests has caused these systems to remain poorly understood. Remote-sensing technology has provided a powerful tool for quantification of structural patterns and associating these with resource use. Satellite and aerial platforms can be used to collect remotely sensed images of tropical forests that can be applied to ecological research and management. Chapter 1 of this article highlights the resources available for tropical forest remote sensing and presents a case-study that demonstrates its application to a neotropical forest located in the Petén region of northern Guatemala. The ancient polity of Tikal has been extensively studied by archaeologists and soil scientists, but little is known about the subsistence and ancient farming techniques that sustained its inhabitants. The objective of chapter 2 was to create predictive models for ancient maize (Zea mays L.) agriculture in the Tikal National Park, Petén, Guatemala, improving our understanding of settlement patterns and the ecological potentials surrounding the site in a cost effective manner. Ancient maize agriculture was described in this study as carbon (C) isotopic signatures left in the soil humin fraction. Probability models predicting C isotopic enrichment and carbonate C were used to outline areas of potential long term maize agriculture. It was found that the Tikal area not only supports a great variety of potential food production systems but the models suggest multiple maize agricultural practices were used.

This research investigates the use of data mining methods for malware (malicious programs) detection and proposed a framework as an alternative to the traditional signature detection methods. The traditional approaches using signatures to detect malicious programs fails for the new and unknown malwares case, where signatures are not available. We present a data mining framework to detect malicious programs. We collected, analyzed and processed several thousand malicious and clean programs to find out the best features and build models that can classify a given program into a malware or a clean class. Our research is closely related to information retrieval and classification techniques and borrows a number of ideas from the field. We used a vector space model to represent the programs in our collection. Our data mining framework includes two separate and distinct classes of experiments. The first are the supervised learning experiments that used a dataset, consisting of several thousand malicious and clean program samples to train, validate and test, an array of classifiers. In the second class of experiments, we proposed using sequential association analysis for feature selection and automatic signature extraction. With our experiments, we were able to achieve as high as 98.4% detection rate and as low as 1.9% false positive rate on novel malwares.

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<p dir="ltr">This research aims to address these critical challenges in uncertainty quantification. The objective is to employ data-driven approaches for UQ with physics models.</p>

High infant mortality (IM) rates in the U.S. have been a major public health concern for decades. Many studies have focused on understanding causes, risk factors, and interventions that can reduce IM. However, death of an infant is the result of the interplay between many risk factors, which in some cases can be traced to the infancy of their parents. Consequently, these complex interactions challenge the effectiveness of many interventions. The long-term goal of this study is to advance the common understanding of effective interventions for improving health outcomes and, in particular, infant mortality. To achieve this goal, I implemented systems and data science methods in three essays to contribute to the understanding of IM causes and risk factors. In the first study, the goal was to identify patterns in the leading causes of infant mortality across states that successfully reduced their IM rates. I explore the trends at the state-level between 2000 and 2015 to identify patterns in the leading causes of IM. This study shows that the main drivers of IM rate reduction is the preterm-related mortality rate. The second study builds on these findings and investigates the risk factors of preterm birth (PTB) in the largest obstetric population that has ever been studied in this field. By applying the latest statistical and machine learning techniques, I study the PTB risk factors that are both generalizable and identifiable during the early stages of pregnancy. A major finding of this study is that socioeconomic factors such as parent education are more important than generally known factors such as race in the prediction of PTB. This finding is significant evidence for theories like Lifecourse, which postulate that the main determinants of a health trajectory are the social scaffolding that addresses the upstream roots of health. These results point to the need for more comprehensive approaches that change the focus from medical interventions during pregnancy to the time where mothers become vulnerable to the risk factors of PTB. Therefore, in the third study, I take an aggregate approach to study the dynamics of population health that results in undesirable outcomes in major indicators like infant mortality. Based on these new explanations, I offer a systematic approach that can help in addressing adverse birth outcomes—including high infant mortality and preterm birth rates—which is the central contribution of this dissertation. In conclusion, this dissertation contributes to a better understanding of the complexities in infant mortality and health-related policies. This work contributes to the body of literature both in terms of the application of statistical and machine learning techniques, as well as in advancing health-related theories. / Doctor of Philosophy / The U.S. infant mortality rate (IMR) is 71% higher than the average rate for comparable countries in the Organization for Economic Co-operation and Development (OECD). High infant mortality and preterm birth rates (PBR) are major public health concerns in the U.S. A wide range of studies have focused on understanding the causes and risk factors of infant mortality and interventions that can reduce it. However, infant mortality is a complex phenomenon that challenges the effectiveness of the interventions, and the IMR and PBR in the U.S. are still higher than any other advanced OECD nation. I believe that systems and data science methods can help in enhancing our understanding of infant mortality causes, risk factors, and effective interventions. There are more than 130 diagnoses—causes—for infant mortality. Therefore, for 50 states tracking the causes of infant mortality trends over a long time period is very challenging. In the first essay, I focus on the medical aspects of infant mortality to find the causes that helped the reduction of the infant mortality rates in certain states from 2000 to 2015. In addition, I investigate the relationship between different risk factors with infant mortality in a regression model to investigate and find significant correlations. This study provides critical recommendations to policymakers in states with high infant mortality rates and guides them on leveraging appropriate interventions. Preterm birth (PTB) is the most significant contributor to the IMR. The first study showed that a reduction in infant mortality happened in states that reduced their preterm birth. There exists a considerable body of literature on identifying the PTB risk factors in order to find possible explanations for consistently high rates of PTB and IMR in the U.S. However, they have fallen short in two key areas: generalizability and being able to detect PTB in early pregnancy. In the second essay, I investigate a wide range of risk factors in the largest obstetric population that has ever been studied in PTB research. The predictors in this study consist of a wide range of variables from environmental (e.g., air pollution) to medical (e.g., history of hypertension) factors. Our objective is to increase the understanding of factors that are both generalizable and identifiable during the early stage of pregnancy. I implemented state-of-the-art statistical and machine learning techniques and improved the performance measures compared to the previous studies. The results of this study reveal the importance of socioeconomic factors such as, parent education, which can be as important as biomedical indicators like the mother's body mass index in predicting preterm delivery. The second study showed an important relationship between socioeconomic factors such as, education and major health outcomes such as preterm birth. Short-term interventions that focus on improving the socioeconomic status of a mother during pregnancy have limited to no effect on birth outcomes. Therefore, we need to implement more comprehensive approaches and change the focus from medical interventions during pregnancy to the time where mothers become vulnerable to the risk factors of PTB. Hence, we use a systematic approach in the third study to explore the dynamics of health over time. This is a novel study, which enhances our understanding of the complex interactions between health and socioeconomic factors over time. I explore why some communities experience the downward spiral of health deterioration, how resources are generated and allocated, how the generation and allocation mechanisms are interconnected, and why we can see significantly different health outcomes across otherwise similar states. I use Ohio as the case study, because it suffers from poor health outcomes despite having one of the best healthcare systems in the nation. The results identify the trap of health expenditure and how an external financial shock can exacerbate health and socioeconomic factors in such a community. I demonstrate how overspending or underspending in healthcare can affect health outcomes in a society in the long-term. Overall, this dissertation contributes to a better understanding of the complexities associated with major health issues of the U.S. I provide health professionals with theoretical and empirical foundations of risk assessment for reducing infant mortality and preterm birth. In addition, this study provides a systematic perspective on the issue of health deterioration that many communities in the US are experiencing, and hope that this perspective improves policymakers' decision-making.