Read Cloud Sequencing Elucidates Microbiome Dynamics in a Stem Cell Transplant Patient
Abstract/Contents
- Abstract
- Low intestinal microbial diversity, often leading to domination of the intestine by a single organism, is associated with poor outcomes following stem cell transplantation. However, the process by which certain organisms achieve domination over others is not well-understood. Previously, it has been difficult to obtain genetic clues as to why the dominating organism has such high fitness in a given circumstance. This is because it has been nearly impossible to obtain near complete genome drafts of the dominating organism without isolation and culturing. Recently, we developed a metagenomic read cloud sequencing approach, which provides significantly improved genome drafts for individual organisms compared to commonly used alternative sequencing methods. Here, we apply read cloud sequencing to stool samples collected longitudinally from a stem cell transplant patient before and after heavy antibiotic exposure across four time points, during which the patient experienced a period of gut domination by E. coli as well as an E. coli bloodstream infection. Comparative genomic analysis reveals that the E. coli strain present in the gut and the E. coli strain isolated from the bloodstream infection are nearly identical (~99.97 nucleotide identity with a difference of 169 SNPs), indicating that the infection likely originated from the gut. Alignment of the pre-transplant E. coli draft genome to the Comprehensive Antibiotic Resistance Database reveals that the pre-transplant E. coli strain (prior to any antibiotic exposure) harbored 55 known resistance genes, including fluoroquinolone resistance and a multitude of multidrug efflux pumps. All other draft genomes from the pre-transplant time point contained <5 resistance genes, suggesting that the E. coli outgrowth was a result of selection after heavy antibiotic exposure. This case study highlights the application of metagenomic read cloud sequencing in a clinical context to investigate microbiome dynamics under extreme selective pressures.
Description
| Type of resource | text |
|---|---|
| Date created | [ca. May 8, 2018] |
Creators/Contributors
| Author | Kang, Joyce Blossom |
|---|---|
| Primary advisor | Bhatt, Ami S. |
| Advisor | Kundaje, Anshul B. |
| Degree granting institution | Stanford University, Department of Computer Science |
Subjects
| Subject | Metagenomics |
|---|---|
| Subject | read cloud sequencing |
| Subject | genome assembly |
| Subject | microbiome |
| Subject | antibiotic resistance |
| Subject | stem cell transplantation |
| Subject | Computer Science |
| Genre | Thesis |
Bibliographic information
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Preferred citation
- Preferred Citation
- Kang, Joyce. (2018). Read Cloud Sequencing Elucidates Microbiome Dynamics in a Stem Cell Transplant Patient. Stanford Digital Repository. Available at: https://purl.stanford.edu/gs785yv8037
Collection
Undergraduate Theses, School of Engineering
View other items in this collection in SearchWorksContact information
- Contact
- joyce.b.kang@gmail.com
Also listed in
Loading usage metrics...