Abstract

Chronic illnesses are poorly understood diseases that are often highly resistant to treatment. The prevalence and severity of these illnesses necessitates new methods for treatment development that diverge from the paradigm of one drug, one illness. Instead, multidrug interventions that utilize repurposable, previously approved drugs could be far more advantageous. In order to support this, a novel scoring framework and accompanying set of tools, collectively termed DrugAble, have been developed. DrugAble scores proposed, model-based treatment target solutions by analyzing drug-target interaction data and addressing the network complexity of these solutions. Actionability scores that summarize the likelihood of a proposed target set constituting a pharmacologically accessible path to remission are generated. Additionally, DrugAble proposes combinations of repurposable drugs that can potentially be used in tandem to achieve remission. Here, DrugAble is demonstrated on molecular target solutions supporting an escape from Myalgic Encephalomyelitis / Chronic Fatigue Syndrome, a debilitating illness that affects up to 2.5 million Americans alone. DrugAble effectively discriminates between theoretical target sets and those that are clinically actionable using available drugs while simultaneously accounting for drug-target interactions and off-target effects of these drugs. This framework constitutes the necessary first steps to designing more effective treatments for chronic illnesses, with the ultimate goal of reducing the failure rate of clinical trials and the financial burden on both drug developers and patients. Most importantly, it opens new and more immediately accessible paths toward achieving remission and full recovery for those suffering from chronic illnesses

Library of Congress Subject Headings

Chronic diseases--Treatment; Pharmaceutical technology; Drug development

Publication Date

4-3-2020

Document Type

Thesis

Student Type

Graduate

Degree Name

Bioinformatics (MS)

Department, Program, or Center

Thomas H. Gosnell School of Life Sciences (COS)

Advisor

Gordon Broderick

Advisor/Committee Member

Matthew Morris

Advisor/Committee Member

Gary Skuse

Campus

RIT – Main Campus

Plan Codes

BIOINFO-MS

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