Investigations into the contribution of retrotransposon activation in neurodegenerative disease

O’Neill, Kathryn Shea (June 2022) Investigations into the contribution of retrotransposon activation in neurodegenerative disease. PhD thesis, Cold Spring Harbor Laboratory.

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This thesis has touched upon multiple fields within transposon biology, small RNA biology, computational biology and applied machine learning. I have published a small RNA analysis pipeline which allows for the facile analysis of small RNA libraries and improved this pipeline in several ways after publication. I performed data analysis to understand the nature of a TDP-43 loss of function mutation on TE associated sRNA biology in human somatic cells. I contributed a review of current computational methods tackling the difficult problem of quantifying highly ambiguous TE derived reads in multiple sequencing-based assays. Finally, I contributed several follow up investigations into the nature of ALS/TDP-43-FTD molecular subtype and constructed a classification algorithm with which new incoming patient samples can be classified. This classifier shows decent generalizability to related datasets, and potential to accurately call subtype on single cell sequencing derived data. From these investigations, I conclude that there is significant room for progress on all fronts touched by this thesis, and am enthusiastic for the continuation of the work. In the following sections I will describe my conception of these frontiers and where I would be most interested in seeing development.

Item Type: Thesis (PhD)
Subjects: diseases & disorders > nervous system diseases and disorders > amyotrophic lateral sclerosis
bioinformatics > computational biology > algorithms > machine learning
diseases & disorders > neurodegenerative diseases
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transposons
CSHL Authors:
Communities: CSHL labs > Hammell M. lab
School of Biological Sciences > Theses
Depositing User: Jannette D'Esposito
Date: 30 June 2022
Date Deposited: 07 Jul 2022 16:01
Last Modified: 07 Jul 2022 16:20

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