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Full-Text Articles in Engineering

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman Jan 2022

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …


Metabolic Modeling Of Multispecies Microbial Biofilms, Poonam Phalak Mar 2020

Metabolic Modeling Of Multispecies Microbial Biofilms, Poonam Phalak

Doctoral Dissertations

Biofilms are ubiquitous in medical, environmental, and engineered microbial systems. The majority of naturally occurring microbes grow as mixed species biofilms. These complicated biofilm consortia are comprised of many cell phenotypes with complex interactions and self-organized into three-dimensional structures. Approximately 2% of the US population suffers from non-healing chronic wounds infected by a combination of commensal and pathogenic bacteria whereas about 500,000 cases of Clostridium difficile infections (CDI) are reported annually. These polymicrobial infections are often resilient to antibiotic treatment due to the nutrient-rich environments and species interactions that promote community stability and robustness. This thesis focusses on developing metabolic …


Revelation Of Yin-Yang Balance In Microbial Cell Factories By Data Mining, Flux Modeling, And Metabolic Engineering, Gang Wu May 2016

Revelation Of Yin-Yang Balance In Microbial Cell Factories By Data Mining, Flux Modeling, And Metabolic Engineering, Gang Wu

McKelvey School of Engineering Theses & Dissertations

The long-held assumption of never-ending rapid growth in biotechnology and especially in synthetic biology has been recently questioned, due to lack of substantial return of investment. One of the main reasons for failures in synthetic biology and metabolic engineering is the metabolic burdens that result in resource losses. Metabolic burden is defined as the portion of a host cells resources either energy molecules (e.g., NADH, NADPH and ATP) or carbon building blocks (e.g., amino acids) that is used to maintain the engineered components (e.g., pathways). As a result, the effectiveness of synthetic biology tools heavily dependents on cell capability to …


Is Metabolism Goal-Directed? Investigating The Validity Of Modeling Biological Systems With Cybernetic Control Via Omic Data, Frank T. Devilbiss Apr 2016

Is Metabolism Goal-Directed? Investigating The Validity Of Modeling Biological Systems With Cybernetic Control Via Omic Data, Frank T. Devilbiss

Open Access Dissertations

Cybernetic models are uniquely juxtaposed to other metabolic modeling frameworks in that they describe the time-dependent regulation of cellular reactions in terms of dynamic "metabolic goals." This approach contrasts starkly with purely mechanistic descriptions of metabolic regulation which seek to explain metabolic processes in high resolution — a clearly daunting undertaking. Over a span of three decades, cybernetic models have been used to predict metabolic phenomena ranging from resource consumption in mixed-substrate environments to intracellular reaction fluxes of intricate metabolic networks. While the cybernetic approach has been validated in its utility for the prediction of metabolic phenomena, its central feature, …