Candidate Name: Katie Jensen
Program: Bioinformatics and Computational Biology​​​​​​​
Committee Chairs: Dr. Jennifer Weller and Dr. Jessica Roseberry​​​​​​​
Committee Members: Dr. Cynthia Gibas, Dr. Kristen Funk, Dr. Anthony Fodor, Dr. Jun-tao Guo, Dr. Shan Yan
Abstract:

There is a need for high-throughput assessment and prediction of nucleic acid secondary structure and base modifications, and a better understanding of how they affect one another in specific conditions such as human disease. Furthermore, there is a need to differentiate among structure-related, chemically modified, or true variant basecalls in genomic and transcriptomic sequencing outcomes.

To address these needs, structured DNA templates were first designed and constructed, then sequenced on the third-generation ONT sequencing platform. Distinct patterns by secondary structure type were revealed, showing promise for application to sequencing projects which rely heavily on precise nucleobase assignments.  Then, next-generation Illumina RNA sequencing data from post-mortem brain tissue of an aged cohort, including Alzheimer’s disease patients, was assessed for epitranscriptomic modifications using a novel approach. Application of this custom methodology uncovered a subset of modifications with important implications for Alzheimer’s disease and aging mechanisms in the brain. These modifications were further assessed for their proximity to and/or predicted effect on structured regions in the RNA transcripts and how this may play a role in Alzheimer’s disease.