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Integrative analyses of diverse biological data sources

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The technology expansion seen in the last decade for genomics research has permitted the generation of large-scale data sources pertaining to molecular biological assays, genomics, proteomics, transcriptomics and other modern omics catalogs. New methods to analyze, integrate and visualize these

The technology expansion seen in the last decade for genomics research has permitted the generation of large-scale data sources pertaining to molecular biological assays, genomics, proteomics, transcriptomics and other modern omics catalogs. New methods to analyze, integrate and visualize these data types are essential to unveil relevant disease mechanisms. Towards these objectives, this research focuses on data integration within two scenarios: (1) transcriptomic, proteomic and functional information and (2) real-time sensor-based measurements motivated by single-cell technology. To assess relationships between protein abundance, transcriptomic and functional data, a nonlinear model was explored at static and temporal levels. The successful integration of these heterogeneous data sources through the stochastic gradient boosted tree approach and its improved predictability are some highlights of this work. Through the development of an innovative validation subroutine based on a permutation approach and the use of external information (i.e., operons), lack of a priori knowledge for undetected proteins was overcome. The integrative methodologies allowed for the identification of undetected proteins for Desulfovibrio vulgaris and Shewanella oneidensis for further biological exploration in laboratories towards finding functional relationships. In an effort to better understand diseases such as cancer at different developmental stages, the Microscale Life Science Center headquartered at the Arizona State University is pursuing single-cell studies by developing novel technologies. This research arranged and applied a statistical framework that tackled the following challenges: random noise, heterogeneous dynamic systems with multiple states, and understanding cell behavior within and across different Barrett's esophageal epithelial cell lines using oxygen consumption curves. These curves were characterized with good empirical fit using nonlinear models with simple structures which allowed extraction of a large number of features. Application of a supervised classification model to these features and the integration of experimental factors allowed for identification of subtle patterns among different cell types visualized through multidimensional scaling. Motivated by the challenges of analyzing real-time measurements, we further explored a unique two-dimensional representation of multiple time series using a wavelet approach which showcased promising results towards less complex approximations. Also, the benefits of external information were explored to improve the image representation.

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2011

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Public health surveillance in high-dimensions with supervised learning

Description

Public health surveillance is a special case of the general problem where counts (or rates) of events are monitored for changes. Modern data complements event counts with many additional measurements (such as geographic, demographic, and others) that comprise high-dimensional covariates.

Public health surveillance is a special case of the general problem where counts (or rates) of events are monitored for changes. Modern data complements event counts with many additional measurements (such as geographic, demographic, and others) that comprise high-dimensional covariates. This leads to an important challenge to detect a change that only occurs within a region, initially unspecified, defined by these covariates. Current methods are typically limited to spatial and/or temporal covariate information and often fail to use all the information available in modern data that can be paramount in unveiling these subtle changes. Additional complexities associated with modern health data that are often not accounted for by traditional methods include: covariates of mixed type, missing values, and high-order interactions among covariates. This work proposes a transform of public health surveillance to supervised learning, so that an appropriate learner can inherently address all the complexities described previously. At the same time, quantitative measures from the learner can be used to define signal criteria to detect changes in rates of events. A Feature Selection (FS) method is used to identify covariates that contribute to a model and to generate a signal. A measure of statistical significance is included to control false alarms. An alternative Percentile method identifies the specific cases that lead to changes using class probability estimates from tree-based ensembles. This second method is intended to be less computationally intensive and significantly simpler to implement. Finally, a third method labeled Rule-Based Feature Value Selection (RBFVS) is proposed for identifying the specific regions in high-dimensional space where the changes are occurring. Results on simulated examples are used to compare the FS method and the Percentile method. Note this work emphasizes the application of the proposed methods on public health surveillance. Nonetheless, these methods can easily be extended to a variety of applications where counts (or rates) of events are monitored for changes. Such problems commonly occur in domains such as manufacturing, economics, environmental systems, engineering, as well as in public health.

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Date Created
2010

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Modeling frameworks for supply chain analytics

Description

Supply chains are increasingly complex as companies branch out into newer products and markets. In many cases, multiple products with moderate differences in performance and price compete for the same unit of demand. Simultaneous occurrences of multiple scenarios (competitive, disruptive,

Supply chains are increasingly complex as companies branch out into newer products and markets. In many cases, multiple products with moderate differences in performance and price compete for the same unit of demand. Simultaneous occurrences of multiple scenarios (competitive, disruptive, regulatory, economic, etc.), coupled with business decisions (pricing, product introduction, etc.) can drastically change demand structures within a short period of time. Furthermore, product obsolescence and cannibalization are real concerns due to short product life cycles. Analytical tools that can handle this complexity are important to quantify the impact of business scenarios/decisions on supply chain performance. Traditional analysis methods struggle in this environment of large, complex datasets with hundreds of features becoming the norm in supply chains. We present an empirical analysis framework termed Scenario Trees that provides a novel representation for impulse and delayed scenario events and a direction for modeling multivariate constrained responses. Amongst potential learners, supervised learners and feature extraction strategies based on tree-based ensembles are employed to extract the most impactful scenarios and predict their outcome on metrics at different product hierarchies. These models are able to provide accurate predictions in modeling environments characterized by incomplete datasets due to product substitution, missing values, outliers, redundant features, mixed variables and nonlinear interaction effects. Graphical model summaries are generated to aid model understanding. Models in complex environments benefit from feature selection methods that extract non-redundant feature subsets from the data. Additional model simplification can be achieved by extracting specific levels/values that contribute to variable importance. We propose and evaluate new analytical methods to address this problem of feature value selection and study their comparative performance using simulated datasets. We show that supply chain surveillance can be structured as a feature value selection problem. For situations such as new product introduction, a bottom-up approach to scenario analysis is designed using an agent-based simulation and data mining framework. This simulation engine envelopes utility theory, discrete choice models and diffusion theory and acts as a test bed for enacting different business scenarios. We demonstrate the use of machine learning algorithms to analyze scenarios and generate graphical summaries to aid decision making.

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Date Created
2012

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Surgical instrument reprocessing in a hospital setting analyzed with statistical process control and data mining techniques

Description

In a healthcare setting, the Sterile Processing Department (SPD) provides ancillary services to the Operating Room (OR), Emergency Room, Labor & Delivery, and off-site clinics. SPD's function is to reprocess reusable surgical instruments and return them to their home departments.

In a healthcare setting, the Sterile Processing Department (SPD) provides ancillary services to the Operating Room (OR), Emergency Room, Labor & Delivery, and off-site clinics. SPD's function is to reprocess reusable surgical instruments and return them to their home departments. The management of surgical instruments and medical devices can impact patient safety and hospital revenue. Any time instrumentation or devices are not available or are not fit for use, patient safety and revenue can be negatively impacted. One step of the instrument reprocessing cycle is sterilization. Steam sterilization is the sterilization method used for the majority of surgical instruments and is preferred to immediate use steam sterilization (IUSS) because terminally sterilized items can be stored until needed. IUSS Items must be used promptly and cannot be stored for later use. IUSS is intended for emergency situations and not as regular course of action. Unfortunately, IUSS is used to compensate for inadequate inventory levels, scheduling conflicts, and miscommunications. If IUSS is viewed as an adverse event, then monitoring IUSS incidences can help healthcare organizations meet patient safety goals and financial goals along with aiding in process improvement efforts. This work recommends statistical process control methods to IUSS incidents and illustrates the use of control charts for IUSS occurrences through a case study and analysis of the control charts for data from a health care provider. Furthermore, this work considers the application of data mining methods to IUSS occurrences and presents a representative example of data mining to the IUSS occurrences. This extends the application of statistical process control and data mining in healthcare applications.

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Date Created
2014

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Spatio-temporal data mining to detect changes and clusters in trajectories

Description

With the rapid development of mobile sensing technologies like GPS, RFID, sensors in smartphones, etc., capturing position data in the form of trajectories has become easy. Moving object trajectory analysis is a growing area of interest these days owing to

With the rapid development of mobile sensing technologies like GPS, RFID, sensors in smartphones, etc., capturing position data in the form of trajectories has become easy. Moving object trajectory analysis is a growing area of interest these days owing to its applications in various domains such as marketing, security, traffic monitoring and management, etc. To better understand movement behaviors from the raw mobility data, this doctoral work provides analytic models for analyzing trajectory data. As a first contribution, a model is developed to detect changes in trajectories with time. If the taxis moving in a city are viewed as sensors that provide real time information of the traffic in the city, a change in these trajectories with time can reveal that the road network has changed. To detect changes, trajectories are modeled with a Hidden Markov Model (HMM). A modified training algorithm, for parameter estimation in HMM, called m-BaumWelch, is used to develop likelihood estimates under assumed changes and used to detect changes in trajectory data with time. Data from vehicles are used to test the method for change detection. Secondly, sequential pattern mining is used to develop a model to detect changes in frequent patterns occurring in trajectory data. The aim is to answer two questions: Are the frequent patterns still frequent in the new data? If they are frequent, has the time interval distribution in the pattern changed? Two different approaches are considered for change detection, frequency-based approach and distribution-based approach. The methods are illustrated with vehicle trajectory data. Finally, a model is developed for clustering and outlier detection in semantic trajectories. A challenge with clustering semantic trajectories is that both numeric and categorical attributes are present. Another problem to be addressed while clustering is that trajectories can be of different lengths and also have missing values. A tree-based ensemble is used to address these problems. The approach is extended to outlier detection in semantic trajectories.

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Date Created
2012

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Machine Learning Models for High-dimensional Biomedical Data

Description

The recent technological advances enable the collection of various complex, heterogeneous and high-dimensional data in biomedical domains. The increasing availability of the high-dimensional biomedical data creates the needs of new machine learning models for effective data analysis and knowledge discovery.

The recent technological advances enable the collection of various complex, heterogeneous and high-dimensional data in biomedical domains. The increasing availability of the high-dimensional biomedical data creates the needs of new machine learning models for effective data analysis and knowledge discovery. This dissertation introduces several unsupervised and supervised methods to help understand the data, discover the patterns and improve the decision making. All the proposed methods can generalize to other industrial fields.

The first topic of this dissertation focuses on the data clustering. Data clustering is often the first step for analyzing a dataset without the label information. Clustering high-dimensional data with mixed categorical and numeric attributes remains a challenging, yet important task. A clustering algorithm based on tree ensembles, CRAFTER, is proposed to tackle this task in a scalable manner.

The second part of this dissertation aims to develop data representation methods for genome sequencing data, a special type of high-dimensional data in the biomedical domain. The proposed data representation method, Bag-of-Segments, can summarize the key characteristics of the genome sequence into a small number of features with good interpretability.

The third part of this dissertation introduces an end-to-end deep neural network model, GCRNN, for time series classification with emphasis on both the accuracy and the interpretation. GCRNN contains a convolutional network component to extract high-level features, and a recurrent network component to enhance the modeling of the temporal characteristics. A feed-forward fully connected network with the sparse group lasso regularization is used to generate the final classification and provide good interpretability.

The last topic centers around the dimensionality reduction methods for time series data. A good dimensionality reduction method is important for the storage, decision making and pattern visualization for time series data. The CRNN autoencoder is proposed to not only achieve low reconstruction error, but also generate discriminative features. A variational version of this autoencoder has great potential for applications such as anomaly detection and process control.

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Date Created
2018