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Diversity in immunocompromised children: the gut microbiome and T cell receptor repertoire

Attenborough, Teresa; (2021) Diversity in immunocompromised children: the gut microbiome and T cell receptor repertoire. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

In this thesis, I apply bioinformatic methods and statistical techniques to three data sets found in immunocompromised paediatric patients, who are receiving haematopoietic stem cell transplants (HSCT) or HIV treatment. In the first part, I examine aspects of the gut microbiome with targeted metagenomics using the 16S rRNA gene. In Chapter 3, I focus on how pre-processing affects the outcomes, and I present and implement a systematic method to identify and remove probable contaminants, leaving the data ready for analysis in Chapter 4. I then examine the changes in the gut microbiomes of a set of paediatric patients undergoing transplants. Many different factors, including specific antibiotic regimes and gut-associated viral infections (i.e. not the transplant alone), appear to affect gut microbiota. Some taxa are differentially abundant when separated by the patients' outcome. In the second part, I analyse aspects of the T cell receptor (TCR) repertoire using high-throughput sequencing. In Chapter 5, I examine the effects of the different methods on the sequenced TCR repertoire. I conclude that biomedical status can affect library size, an effect which would be concealed by subsampling. I find that some clonotypes come from distinct recombination events. In Chapter 6, I track TCR repertoire diversity following transplants from umbilical cord blood (UCB). The recovery of TCR diversity was highly variable, although the majority of patients returned to normality around 12 months post-transplant. This study contributes to the characterisation of the recovery trajectory from UCB HSCT, and supports UCB as a viable source for HSCT. In Chapter 7, I examine the effects of a planned treatment interruption for children living with HIV. While the immune profile returned in many respects to a pattern similar to that of children without an interruption, there may be some long-term effects on the diversity of the TCR repertoire.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Diversity in immunocompromised children: the gut microbiome and T cell receptor repertoire
Event: UCL (University College London)
Language: English
Additional information: Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science > CoMPLEX: Mat&Phys in Life Sci and Exp Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10129344
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