UC San Diego

The current state of the world – stricken by a Coronavirus pandemic that spread across the globe harming millions of lives in a matter of months – is a humbling reminder that we have barely scraped the surface of understanding complex biological systems.

The central theme of this work is the idea that human health is a function of many complex biological machineries working synergistically, together constituting the human superorganism. The dissertation begins with a description of the computational advancements required to understand the complexity of the human microbiota and its role in human health; this is followed by a review of the role of our commensal microbiota in nonalcoholic steatohepatitis, alcoholic steatohepatitis and liver cirrhosis, and hepatocellular carcinoma.

Chapters 2, 3, and 4 report original research studies highlighting the potential of leveraging high-throughput molecular assays and supervised algorithms to develop new microbiome-based diagnostic, prognostic, and therapeutic modalities to improve the management of metabolic diseases. These chapters also underscore the importance of multi-omics approaches to probe biological systems for a system-wide understanding.

Chapter 5 introduces Qemistree – a new tool that adapts statistical concepts from microbial ecology for the analysis of high-dimensional metabolomics data. Qemistree underscores the importance of mapping existing analytical solutions across omics domains in order to integrate heterogeneous data layers and comprehensively understand biological systems.