Life Sciences Commons^™

Process Mining Of Medication Revisions In Electronic Health Records, Deevakar Rogith

Dissertations & Theses (Open Access)

Objective: The objective of this work is to develop process mining techniques for analysing Electronic Health Record (EHR) events in order to uncover factors contributing to the event, and understanding deviations in the process. We have outlined a method for combining data mining with expert review to model the EHR process and develop automated algorithms that can be used to detect potential deviations for a defined process.

Introduction: To analyse EHR events meaningfully, process mining can be applied to distil structured process description from a set of real executions. Process mining can be applied for 1) Discovery, 2) Conformance, and …

Designing For Practice Development In A Social Learning System: Communicating Norms And Vicarious Experience, Claire Loe

Dissertations & Theses (Open Access)

Over the past quarter century, the United States has experienced an increase in demand for health services. Expanded use of community health workers (CHWs) has been identified as a strategic response for more effective distribution of healthcare resources by alleviating pressures on clinical personnel and infusing prevention education into the community-to-clinical care continuum. Expansion of the CHW workforce poses many challenges. For CHWs to effectively reduce costs and pressures on the healthcare system, ‘expansion’ implies not only increasing their numbers, but also assuring a workforce that has the capacity to perform in diverse settings. I propose a theoretical framework for …

Germline Mutation Detection In Next Generation Sequencing Data And Tp53 Mutation Carrier Probability Estimation For Li-Fraumeni Syndrome, Gang Peng

Dissertations & Theses (Open Access)

Next generation sequencing technology has been widely used in genomic analysis, but its application has been compromised by the missing true variants, especially when these variants are rare. We proposed a family-based variant calling method, FamSeq, integrating Mendelian transmission information with de novo mutation and sequencing data to improve the variant calling accuracy. We investigated the factors impacting the improvement of family-based variant calling in simulation data and validated it in real sequencing data. In both simulation and real data, FamSeq works better than the single individual based method.

In FamSeq, we implemented four different methods for the Mendelian genetic …

Detection Of Genes Influencing Chronic And Mendelian Disease Via Loss-Of-Function Variation, Alexander H. Li

Dissertations & Theses (Open Access)

A typical human exome harbors dozens of loss-of-function (LOF) variants predicted to severely disrupt or abolish gene function. These variants are enriched at the extremely rare end of the allele frequency spectrum (< 0.1%), suggesting purifying selection against these sites. However, most previous population-based sequencing studies have not included analysis of genotype-phenotype relationships with LOF variants. Thus, the contribution of LOF variation to health and disease within the general population remains largely uncharacterized.

Using whole exome sequence from 8,554 participants in the Atherosclerosis Risk in Communities (ARIC) study, we explored the impact of LOF variation on a broad spectrum of human phenotypes. First, we selected 20 common chronic disease risk factor phenotypes and performed gene-based association tests. Analysis of this sample verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Novel relationships included …

Identification Of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing, Timothy B. Palculict

Dissertations & Theses (Open Access)

Wilms tumor, a childhood tumor arising from undifferentiated renal mesenchyme, is diagnosed in North America at a frequency of 1 in 10,000 live births and accounts for 5% of all pediatric cancers. The etiology of Wilms tumor is heterogeneous with multiple genes known to have an effect on Wilms tumor development; however, these genes are rarely associated with familial Wilms tumor. Gene mutations in WT1, WTX, CTNNB1 and TP53 are observed in a third of sporadic tumors, while the causative gene(s) responsible for familial Wilms tumor are largely unknown. Approximately 2% of Wilms tumor patients have a family …

Investigating The Interaction Of Aurka And Ube2c In Colorectal Cancer Cells, Apurva M. Hegde

Dissertations & Theses (Open Access)

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Among the many genomic aberrations previously implicated in colorectal cancer, recurrent amplification of chromosome 20q is frequently associated with liver metastasis. Previous research in our lab identified a gene signature on chromosome 20q associated with colorectal cancer progression. In this study, one of the genes in the signature, the ubiquitin conjugating enzyme UBE2C, was identified through preliminary bioinformatics analysis as a candidate for further examination of its role in CRC progression. Co-expression analysis of UBE2C in tumor-normal datasets from the public database Oncomine revealed all the …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations & Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

Measuring Single Cell Responses To Lapatinib In A Heterogeneous Population, Preety Priya

Dissertations & Theses (Open Access)

Cancer is notonedisease butasaga of diseases and is the outcome of disturbed homeostasis in the normal cells due to the deregulation of its genetic makeup. With advent of technologies thatallowdetailed molecular characterizationoftumors, targeted therapies have emerged as a more promising and specific mode of treatment. However, a major challenge with targeted therapy is the acquired resistance in the cancer cells to these therapies, quite often very rapidly in the course of a few months. One of the major targets in cancer has been the EGFR/ErbB2 network in breast and other cancer types. Prior work from our lab and others have …