Matching Items (7)
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Description

Urologic diseases interstitial cystitis (IC), overactive bladder (OAB), and urinary tract infection (UTI) affect tens of millions of people per year in the US alone. The human microbiome consists of a diverse community of bacteria (bacteriome) and viruses (virome) harbored in each individual that contributes to health and disease. Little

Urologic diseases interstitial cystitis (IC), overactive bladder (OAB), and urinary tract infection (UTI) affect tens of millions of people per year in the US alone. The human microbiome consists of a diverse community of bacteria (bacteriome) and viruses (virome) harbored in each individual that contributes to health and disease. Little is known about how the microbiome impacts urinary disorders. Using next-generation metagenomic sequencing, we characterized the urinary bacteriome and virome of patients with urinary disorders (IC, OAB, and UTI) and healthy controls. We show that the bacteriome was distinctly altered in patients by their respective urinary disorder. IC was characterized by a distinct prevalence of the genus Lactobacillus, while OAB was characterized by the genus Bacteroides, and UTI was characterized by Comamonas. IC, OAB, and UTI all also had significantly differed virome profiles from healthy individuals. In particular, we found that Lactobacillus phages were significantly associated with IC and Corynebacterium virus was associated with UTI samples, meanwhile no particular virus was correlated with OAB samples. Overall, we show that changes in the urinary microbiome are associated with incidence and spectrum of urinary diseases. These findings could lead to new microbiome modalities of treatment.

ContributorsBains, Ajeet (Author) / Lim, Efrem (Thesis director) / Zhu, Qiyun (Committee member) / Kaelin, Emily (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft

The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft rejection. It has been hypothesized that the localized microbiota in each organ produce metabolites that instigate inflammatory immune responses, but whether microbiota interactions precipitate acute allograft rejection is unknown. Therefore, this study focuses on microbiome shifts in the gut and kidney after inducing acute renal transplant rejection in order to implicate gut dysbiosis as a precursor or supporter of allograft rejection. This study also subsequently explores the use of an immune-modulating protein in order to determine differences in the outcome of transplant rejection and potential differences in intestinal microbial load. This experiment sought to induce rejection in BALB/c mice through the use of C57BL/6 mouse renal slivers. Microbiome abundance was analyzed in all experimental groups. Understanding the role of the microbiome in transplant rejection has vast clinical implications and has the potential to enhance pre- and post-operative treatment, and immune management and quality of life following organ transplant.

ContributorsKokott, Kristiana Tara (Author) / Lim, Efrem (Thesis director) / Lucas, Alexandra (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

On March 11th, COVID-19 was declared a pandemic by the World Health Organization. The ensuing months saw an extensive allocation of resources toward combating the virus and the development of a vaccine. Despite extensive research on SARS-CoV-2, there remains little information regarding the implications of SARS-CoV-2 gastrointestinal shedding on COVID-19

On March 11th, COVID-19 was declared a pandemic by the World Health Organization. The ensuing months saw an extensive allocation of resources toward combating the virus and the development of a vaccine. Despite extensive research on SARS-CoV-2, there remains little information regarding the implications of SARS-CoV-2 gastrointestinal shedding on COVID-19 disease. It is hypothesized that SARS-CoV-2 RNA is shed in the stool for up to several weeks and that viral protein persists in the GI tract. This study also explored calprotectin and zonulin levels, markers of inflammation, and intestinal permeability, respectively, to assess if increased viral shedding is associated with elevated levels of either. This study utilized RT-qPCR assays to confirm the presence of viral RNA. Subsequently, RT-qPCR positive samples were heat-inactivated and SARS-CoV-2 spike detection enzyme-linked immunosorbent assay (ELISA) was used to ascertain viral protein shedding. Additional ELISA was performed to assess zonulin and calprotectin levels. Results indicated that 30 of the 758 unique samples were confirmed SARS-CoV-2 positive by RT-qPCR. Spike protein was ultimately not detected by ELISA. Additionally, no significant increase in zonulin was observed in patient samples when comparing RT-qPCR positive and negative Samples. A notable upwards trend approaching significance in calprotectin levels existed for patients who tested positive for SARS-CoV-2 by RT-qPCR, though, it was found that no correlation existed between SARS-CoV-2 copy number and calprotectin levels. Understanding the interaction between SARS-CoV-2 and the GI tract may therefore have significant clinical implications and this study demonstrates the need for additional studies to garner a more comprehensive understanding.

ContributorsKhan, Adam (Author) / Lim, Efrem (Thesis director) / Li, Yize (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2022-05
Description

The microbiome and virome are known to interact within the human body which in turn modulates the health and disease of an individual. While these interactions have been largely studied in bodily sites such as the gastrointestinal tract, the microbiome and virome of the female genital tract (FGT) remains largely

The microbiome and virome are known to interact within the human body which in turn modulates the health and disease of an individual. While these interactions have been largely studied in bodily sites such as the gastrointestinal tract, the microbiome and virome of the female genital tract (FGT) remains largely understudied. Within the virome exists DNA and RNA viruses which are known to infect both eukaryotes and prokaryotes. While existing virome research within the FGT has focused largely on eukaryote infecting viruses, a large proportion of the virome consists of uncharacterized bacteriophages known as “dark matter”. Due to the lack of a specific gene marker for viruses, which is essential in qPCR quantification of other populations such as bacteria, determination of viral abundance and virome characterization has been limited. However, the staining of viral DNA has been found effective in visualizing and enumerating virus-like particles within various specimens. In this study, we seek to determine viral abundance within the FGT utilizing SYBR Gold nucleic acid stain to visualize VLP present within a cohort of cervicovaginal lavage (CVL) samples. Given these results we intend to draw conclusions regarding the interactions between the FGT virome and viral abundance as well as sexual-reproductive health. Understanding the complex relationship of the virome within the female reproductive tract is likely to have remarkable clinical implications and has the potential to progress both the diagnostic and treatment aspects of female sexual and reproductive health.

ContributorsFredenberg, Mara (Author) / Lim, Efrem (Thesis director) / Kaelin, Emily (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2023-05
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Description
Human leukocyte antigen (HLA) is a group of proteins that the human immune system uses to detect pathogens. HLA is highly polymorphic, especially in the peptide-binding groove, which allows the binding of a diverse range of peptides including peptides produced by pathogens. Hepatitis B virus (HBV), is a pathogen that

Human leukocyte antigen (HLA) is a group of proteins that the human immune system uses to detect pathogens. HLA is highly polymorphic, especially in the peptide-binding groove, which allows the binding of a diverse range of peptides including peptides produced by pathogens. Hepatitis B virus (HBV), is a pathogen that can cause liver disease. Chronic HBV infection, if left untreated, can lead to hepatocellular carcinoma, the most common form of liver cancer. In this paper, the association of Class I and II HLA with HBV-mediated liver cancer in patients of East Asian and European ancestry was studied. Results showed that, in the initial combined ancestry analysis, some alleles from all HLA types are associated with HBV-mediated liver cancer. However, once stratified by population ancestry, most of the alleles are no longer significant but still associate with HBV-mediated liver cancer in the same directions. In contrast, HLA-DP is the only HLA with haplotypes that are significantly different before and after stratification by ancestry. Notably, DPA10103-DPB10401, a previously known protective haplotype in the Asian population, is associated negatively with HBV-mediated liver cancer in both East Asian and European populations. Additionally, DPA10202-DPB10501, a known risk haplotype in the Asian population, is associated positively with HBV-mediated liver cancer patients of European ancestry. To understand how HLA-DP is associated with HBV-mediated liver cancer, the binding affinity of HLA-DP to all peptides generated from HBV coding sequences of genotypes A-H was predicted. It was speculated that an individual with HLA types that can bind strongly to HBV peptides will be more likely to clear viral infection whereas an individual with HLA types that fail to bind strongly to HBV peptides will be less likely to clear viral infection, thus developing chronic infection. Results showed that DPA10103-DPB10401 binds strongly to HBV peptides (<50nM) whereas DPA10202-DPB10501 does not bind strongly to any HBV peptides (>50nM), consistent with the speculation that the binding affinity of HBV peptides to HLA will influence the association of HLA with HBV-mediated liver cancer.
ContributorsYap, Yan Rou (Author) / Wilson, Melissa (Thesis advisor) / Lim, Efrem (Thesis advisor) / Buetow, Kenneth (Committee member) / Arizona State University (Publisher)
Created2021
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Description

We identified Torque teno indri virus 1 (TTIV1), the first anellovirus in a free-living lemur (Indri indri). The complete circular 2,572-nucleotide (nt) TTIV1 genome is distantly related to torque teno sus virus. Phylogenetic and sequence analyses support TTIV1 as a putative member of a new genus within the Anelloviridae family.

ContributorsAmatya, Rina (Author) / Deem, Sharon L. (Author) / Porton, Ingrid J. (Author) / Wang, David (Author) / Lim, Efrem (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-07-27
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Description
Metagenomics is the study of the structure and function of microbial communities through the application of the whole-genome shotgun (WGS) sequencing method. Providing high-resolution community profiles at species or even strain levels, metagenomics points to a new direction for microbiome research in understanding microbial gene function, microbial-microbial interactions, and host-microbe

Metagenomics is the study of the structure and function of microbial communities through the application of the whole-genome shotgun (WGS) sequencing method. Providing high-resolution community profiles at species or even strain levels, metagenomics points to a new direction for microbiome research in understanding microbial gene function, microbial-microbial interactions, and host-microbe interactions. My thesis work includes innovation in metagenomic research through the application of ChatGPT in assisting beginning researchers, adopt pre-existed alpha diversity metric for metagenomic data to improve diversity calculation, and the application of metagenomic data in Alzheimer’s disease research.Since the release of ChatGPT in March 2023, the conversation regarding AI in research has promptly been debated. Through the prompted bioinformatic case study, I demonstrate the application of ChatGPT in conducting metagenomic analysis. I constructed and tested a working pipeline aimed at instructing GPT in completing shotgun metagenomic research. The pipeline includes instructions for various essential analytic steps: quality controls, host filtering, read classification, abundance estimation, diversity calculation, and data visualization. The pipeline demonstrated successful completion and reproducible results. Alpha diversity measurement is critical to understanding microbiomes. The widely used Faith’s phylogenetic diversity (PD) metric is agnostic of feature abundance and, therefore, falls short of analyzing metagenomic data. BWPDθ, an abundance weighted variant of Faith’s PD, was implemented in scikit-bio alpha diversity metrics. My analysis shows that BWPDθ does have better performance compared to Faith’s PD, revealing more biological significance, and maintaining their robustness at a lower sampling depth. The progression of Alzheimer’s disease (AD) is known to be associated with alterations in the patient’s gut microbiome. Utilizing metagenomic data from the AlzBiom study, I explored the differential abundance of bacterial pncA genes among healthy and AD participants by age group. The analysis showed that there was no significant difference in pncA abundance between the healthy and AD patients. However, when stratified by age group, within the age group 64 to 69, AD was shown to have significantly lower pncA abundance than the healthy control group. The Pearson's test showed a moderate positive association between age and pncA abundance.
ContributorsXing, Zhu (Author) / Zhu, Qiyun (Thesis advisor) / Lim, Efrem (Committee member) / Snyder-Mackler, Noah (Committee member) / Arizona State University (Publisher)
Created2024