Faculty Proceedings, Presentations, Speeches and Lectures

Title

From Gene Expression to Multisystem Regulation: Identifying Optimal Treatment Courses for Complex Chronic Illnesses

Event Location / Date(s)

Geelong, Victoria, Australia / 2019-03-12 - 2019-03-14

Document Type

Invited Presentation

Presentation Date

3-12-2019

Conference Name / Publication Title

2019 Emerge Australia International Research Symposium: "The Biomedical Basis, Diagnosis, Treatment and Management"

Description

Discovering novel treatment strategies for complex chronic illnesses through traditional discovery pipelines is extremely expensive, carries a high probability of failure, and a lengthy cycle time. Furthermore, it is becoming clear that “one target, one treatment” solutions may not be capable of addressing difficult conditions. Repurposing Food and Drug Administration approved drugs offers a costeffective solution with a significantly abbreviated timeline. Furthermore, combining multi-system modeling with these bioinformatics techniques can harness the regulatory dynamics of the human body to identify robust treatment courses that might produce lasting remission. Here it will be discussed how differentially expressed gene modules cross-referenced with drug atlas and pharmacogenomic databases can be used to identify targetable systems and agents. Based on these results it will be discussed how to construct a discrete ternary logic representation of signaling networks from physiological and biochemical literature to provide a qualitative description of multi-system behavior. By exploiting the regulatory dynamics of the resulting model through the application of a combinatorial optimization scheme and Monte Carlo simulation, it will be discussed how to predict treatment courses that might produce lasting disease remission. While the methods presented here can be applied generally, they will be discussed in the context of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, a debilitating chronic multi-symptom disorder for which there is no known treatment.

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