Date of Award

January 2023

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Leah Ferrucci

Second Advisor

Kim Blenman

Abstract

Background: IgM and IgG autoantibodies are present in healthy humans and there are also unique autoantibodies that make up the majority of autoantibodies present in the human body. The primary objective of this study was to identify proteins that are consistently expressed at baseline levels in healthy patients, with the intention of establishing a set of shared or common proteins that can be targeted for further investigation in future research endeavors.Methods: We utilized autoantibody profiling data from 100 samples of 54 unique patients enrolled in a breast cancer screening center in New York City. The autoantibody profiling data was generated from the HuProt™ human proteome microarray from CDI Lab (Mayaguez, Puerto Rico), which canvases >80% of the entire human proteome. Results: Microarray data was subjected to analysis using DeSeq2 software, as the originally intended R package limma was unable to accurately read the gpr files due to issues with version formatting. To surmount this challenge, data.table was employed to exclude metadata and process the data, resulting in the generation of matrices for SNR values and standard deviation scores. To account for the presence of multiple clones in the datasets, we calculated averaged SNR values for each protein. Significant alterations in the file structure including these processing and other steps were not only necessary but critical in enabling us to analyze the data downstream. We found that roughly 17% of autoantibodies in healthy patients are shared. Additionally, we found that each patient has a unique autoantibody profile. Conclusions: At present, there is a lack of information available to compare immune responses across patients. However, our project has made significant strides in this area by identifying common autoantibodies that are shared among healthy individuals. These autoantibodies could potentially serve as reference standards or housekeeping markers for comparing immune responses between patients.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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