From genomes to populations : measuring the microbiome at small and large scales

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Abstract/Contents

Abstract
A comprehensive understanding of the presence, function, and variation of gut mi- crobiomes across populations is important for relating the gut microbiome and hu- man health. However, most efforts in the microbiome field have been grounded in fragmented microbial reference genomes derived from a non-representative sub- set of the world's population. These limitations can constrain associations between genome-level and population-level microbial variation and downstream effects on hu- man health and disease. This dissertation focuses on leveraging cutting-edge metage- nomics approaches to more accurately and comprehensively measure human gut mi- crobes. I present five projects that collectively detail the characterization of the gut microbiome across biological and experimental scales, from building complete mi- crobial genomes to measuring microbiome variation across global cohorts. Chapter 1 provides an introduction to the current state and recent advances in microbiome research. Chapter 2 details molecular and computational pipelines to recover com- plete, contiguous microbial genomes from metagenomes, which represents a significant technical advance. Chapter 3 further describes these protocols in a detailed and ac- cessible manner to enable broader research in this space. Chapter 4 presents the first application of a new synthetic long-read sequencing assay to the problem of metagenomic assembly. Transitioning more broadly to accurate microbial measure- ment on experimental and methodological scales, Chapter 5 compares how sample preservation methods introduce experimental bias and affect microbial concentration quantification. Finally, widening scope to the measurement of microbiome variation across global populations, Chapter 6 presents a study of the gut microbiome of two South African populations and places their microbiome composition in global con- text. Together, these studies advance our ability to measure microbiomes, through building accurate microbial genome representations, thoughtfully considering study design and the importance of measured variables, and providing a concrete framework for conducting community-engaged, large-scale global studies.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2023; ©2023
Publication date 2023; 2023
Issuance monographic
Language English

Creators/Contributors

Author Maghini, Dylan Gabriele
Degree supervisor Bhatt, Ami (Ami Siddharth)
Thesis advisor Bhatt, Ami (Ami Siddharth)
Thesis advisor Good, Benjamin H
Thesis advisor Sherlock, Gavin
Thesis advisor Sidow, Arend
Degree committee member Good, Benjamin H
Degree committee member Sherlock, Gavin
Degree committee member Sidow, Arend
Associated with Stanford University, School of Medicine
Associated with Stanford University, Department of Genetics

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Dylan Maghini.
Note Submitted to the Department of Genetics.
Thesis Thesis Ph.D. Stanford University 2023.
Location https://purl.stanford.edu/jw286dr8020

Access conditions

Copyright
© 2023 by Dylan Gabriele Maghini
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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