GSBS Dissertations and Theses

ORCID ID

0000-0001-7690-0230

Publication Date

2019-04-30

Document Type

Doctoral Dissertation

Academic Program

Bioinformatics and Computational Biology

Department

Program in Bioinformatics and Integrative Biology

First Thesis Advisor

Jeffrey A. Bailey

Keywords

EBV, Cancer, miRNAs, EBERs, Epidemiology, Acute Myeloid Leukemia (AML), Stomach Cancer, Endemic Burkitt Lymphoma (eBL)

Abstract

Viruses are known to be associated with 20% of human cancers. Epstein Barr virus (EBV) in particular is the first virus associated with human cancers. Here, we computationally detect EBV and explore the effects of this virus across cancers by taking advantage of the fact that EBV microRNAs (miRNAs) and Epstein Barr virus small RNAs (EBERs) are expressed at all viral latencies. We identify and characterize two sub-populations of EBV positive tumors: those with high levels of EBV miRNA and EBERS expression and those with medium levels of expression.

Based on principal component analysis (PCA) and hierarchical clustering of viral miRNAs across all samples we observe a pattern of expression for these EBV miRNAs which is correlated with both the tumor cell type (B cell versus epithelial cell) and with the overall levels of expression of these miRNAs.

We further investigated the effect of the levels of EBV miRNAs with the overall survival of patients across cancers. Through Kaplan Meier survival analysis we observe a significant correlation with levels of EBV miRNAs and lower survival in adult AML patients. We also designed a machine learning model for risk assessment of EBV in association with adult AML and other clinical factors.

Our next aim was to identify targets of EBV miRNAs, hence, we used a combination of previously known methodologies for miRNA target detection in addition to a multivariable regression approach to identify targets of these viral miRNAs in stomach cancer.

Finally, we investigate the variations across EBV subtype specific EBNA3C gene which interacts with the host immune system. Preliminary data suggests potential regional variations plus higher pathogenicity of subtype 1 in comparison to subtype 2 EBV.

Overall, these studies further our understanding of how EBV manipulates the tumor microenvironment across cancer subtypes.

DOI

10.13028/nfs6-2431

Rights and Permissions

Licensed under a Creative Commons license

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Available for download on Monday, June 01, 2020

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