Graduate Thesis Or Dissertation
 

Development and implementation of a transkingdom network analysis pipeline to identify drivers of disease

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/vd66w7907

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  • The gut microbiome has been previously implemented in a number of diseases. Of note is its substantial role in metabolic syndrome, which encapsulates a group of conditions that increase the risk of cardiovascular disease, type 2 diabetes, and stroke. Understanding the causal relationships between the gut microbiome and host processes that influence disease has proved challenging, as the availability of easy-to-use software that does not require large sample sizes is lacking. As such, my work has aimed to develop a software pipeline called transkingdom network analysis (TkNA) that models biological systems from multi-omic data, using a top-down network biology approach. I then sought to utilize TkNA on real-world data to identify microbiota responsible for the anti-inflammatory effects of tetrahydroxanthohumol (TXN), which were previously identified in mice. Mice in the TXN study were raised on either a low-fat diet or a high-fat diet, with or without TXN treatment, and the TkNA pipeline was used to analyze the resulting microbial, transcriptomic, metabolic, and phenotypic outcomes. As a result, I was able to identify the adipose tissue as one of the key tissues affected by TXN treatment, specifically myeloid cells that are responsible for inflammatory responses. In addition, I showed TXN improved levels of many microbes. Specifically, the network reconstruction and interrogation capabilities of TkNA were used to identify a microbe belonging to the Oscillibacter genus that played a causal role in the development of high fat diet induced metabolic disease. This work was then experimentally validated in vitro using macrophage cell lines. This new software using existing analytical ideas and principles of causality, combined with the evidence that it can find causal factors in disease, lays the foundation for future work to study additional diseases.
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  • Morgun/Shulzhenko lab website:
  • TkNA GitHub repo:
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  • Pending Publication
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  • 2023-09-08 to 2024-04-09

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