Doctor of Philosophy / Department of Electrical and Computer Engineering / Sanjoy Das and Anil Pahwa / Because a majority of day-to-day activities rely on electricity, it plays an important role in daily life. In this digital world, most of the people’s life depends on electricity. Without electricity, the flip of a switch would no longer produce instant light, television or refrigerators would be nonexistent, and hundreds of conveniences often taken for granted would be impossible. Electricity has become a basic necessity, and so any interruption in service due to disturbances in power lines causes a great inconvenience to customers. Customers and utility commissions expect a high level of reliability. Power distribution systems are geographically dispersed and exposure to environment makes them highly vulnerable part of power systems with respect to failures and interruption of service to customers. Following the restructuring and increased competition in the electric utility industry, distribution system reliability has acquired larger significance. Better understanding of causes and consequences of distribution interruptions is helpful in maintaining distribution systems, designing reliable systems, installing protection devices, and environmental issues. Various events, such as equipment failure, animal activity, tree fall, wind, and lightning, can negatively affect power distribution systems. Weather is one of the primary causes affecting distribution system reliability. Unfortunately, as weather-related outages are highly random, predicting their occurrence is an arduous task. To study the impact of weather on overhead distribution system several models, such as linear and exponential regression models, neural network model, and ensemble methods are presented in this dissertation. The models were extended to study the impact of animal activity on outages in overhead distribution system. Outage, lightning, and weather data for four different cities in Kansas of various sizes from 2005 to 2011 were provided by Westar Energy, Topeka, and state climate office at Kansas State University weather services. Models developed are applied to estimate daily outages. Performance tests shows that regression and neural network models are able to estimate outages well but failed to estimate well in lower and upper range of observed values. The introduction of committee machines inspired by the ‘divide & conquer” principle overcomes this problem. Simulation results shows that mixture of experts model is more effective followed by AdaBoost model in estimating daily outages. Similar results on performance of these models were found for animal-caused outages.

Missense mutations account for more than 50% of the mutations known to be involved in human inherited diseases. Missense classification is a challenging task that involves sequencing of the genome, identifying the variations, and assessing their deleteriousness. This is a very laborious, time and cost intensive task to be carried out in the laboratory. Advancements in bioinformatics have led to several large-scale next-generation genome sequencing projects, and subsequently the identification of genome variations. Several studies have combined this data with information on established deleterious and neutral variants to develop machine learning based classifiers. There are significant issues with the missense classifiers due to which missense classification is still an open area of research. These issues can be classified under two broad categories: (a) Dataset overlap issue - where the performance estimates reported by the state-of-the-art classifiers are overly optimistic as they have often been evaluated on datasets that have significant overlaps with their training datasets. Also, there is no comparative analysis of these tools using a common benchmark dataset that contains no overlap with the training datasets, therefore making it impossible to identify the best classifier among them. Also, such a common benchmark dataset is not available. (b) Inadequate capture of vital biological information of the protein and mutations - such as conservation of long-range amino acid dependencies, changes in certain physico-chemical properties of the wild-type and mutant amino acids, due to the mutation. It is also not clear how to extract and use this information. Also, some classifiers use structural information that is not available for all proteins. In this study, we compiled a new dataset, containing around 2 - 15% overlap with the popularly used training datasets, with 18,036 mutations in 5,642 proteins. We reviewed and evaluated 15 state-of-the-art missense classifiers - SIFT, PANTHER, PROVEAN, PhD-SNP, Mutation Assessor, FATHMM, SNPs&GO, SNPs&GO3D, nsSNPAnalyzer, PolyPhen-2, SNAP, MutPred, PON-P2, CONDEL and MetaSNP, using the six metrics - accuracy, sensitivity, specificity, precision, NPV and MCC. When evaluated on our dataset, we observe huge performance drops from what has been claimed. Average drop in the performance for these 13 classifiers are around 15% in accuracy, 17% in sensitivity, 14% in specificity, 7% in NPV, 24% in precision and 30% in MCC. With this we show that the performance of these tools is not consistent on different datasets, and thus not reliable for practical use in a clinical setting. As we observed that the performance of the existing classifiers is poor in general, we tried to develop a new classifier that is robust and performs consistently across datasets, and better than the state-of-the-art classifiers. We developed a novel method of capturing long-range amino acid dependency conservation by boosting the conservation frequencies of substrings of amino acids of various lengths around the mutation position using AdaBoost learning algorithm. This score alone performed equivalently to the sequence conservation based tools in classifying missense mutations. Popularly used sequence conservation properties was combined with this boosted long-range dependency conservation scores using AdaBoost algorithm. This reduced the class bias, and improved the overall accuracy of the classifier. We trained a third classifier by incorporating changes in 21 important physico-chemical properties, due to the mutation. In this case, we observed that the overall performance further improved and the class bias further reduced. The performance of our final classifier is comparable with the state-of-the-art classifiers. We did not find any significant improvement, but the class-specific accuracies and precisions are marginally better by around 1-2% than those of the existing classifiers. In order to understand our classifier better, we dissected our benchmark dataset into: (a) seen and unseen proteins, and (b) pure and mixed proteins, and analysed the performance in detail. Finally we concluded that our classifier performs consistently across each of these categories of seen, unseen, pure and mixed protein.