Theses and Dissertations

Date of Award

5-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Computer Science

First Advisor

Dr. Marzieh Ayati

Second Advisor

Dr. Zhixiang Chen

Third Advisor

Dr. Andres Figueroa

Abstract

Mass spectrometry-based proteomics is a powerful tool for identifying post-translational modifications (PTMs) across the proteome. O-GlcNAcylation and phosphorylation are two PTMs that play crucial roles in regulating cellular processes, including cardiac contractile function. Dysregulation of these PTMs has been implicated in the development and progression of diabetic cardiomyopathy. In this study, we aimed to investigate the interplay between O-GlcNAcylation and phosphorylation in healthy and type 2 diabetic hearts, with a specific focus on the functional relationships between these PTMs and their potential therapeutic implications.

Utilizing mass spectrometry data, we identified and quantified specific PTMs on myofilament proteins, uncovering 1354 O-GlcNAcylated sites in 361 proteins and 5973 phosphorylated sites in 2347 proteins. Additionally, we identified 237 unique proteins that had both phosphorylation and O-GlcNAcylation data. After normalizing both datasets based on protein expression levels, we performed a comprehensive analysis of the correlation between phosphorylation and O-GlcNAcylation, revealing significant relationships across all pairs of phosphosites and O-GlcNAc sites within a study.

Our analysis of the intra-protein sequence proximity and inter-protein distance effects on these correlations demonstrated that closely positioned intra-protein sites have higher correlation, and in three cases, the correlation decreases when inter-protein distance increases. These findings provide valuable insights into the molecular mechanisms underlying the interplay between O-GlcNAcylation and phosphorylation in cardiac function, suggesting potential therapeutic targets for diabetic cardiomyopathy.

Comments

Copyright 2023 Amit Das. All Rights Reserved.

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