Understanding mammalian biology and disease through tissue-specific protein-protein interaction networks
department or school: Science, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Skinnider, Michael
issued: 2021-05-31T17:26:29Z
issued: 2021
related degree: Doctor of Medicine / Doctor of Philosophy - MD/PhD
degree grantor: University of British Columbia
description: Biological functions are mediated by the dynamic organization of DNA, RNA, proteins, and other biomolecules in complex networks of interactions. Efforts to chart the network of biologically relevant macromolecular interactions—the “interactome”—therefore occupy a central position in the endeavour to understand the biochemical basis of human physiology, and its perturbation in disease. However, existing interactome maps are incomplete, even for well-studied organisms. Moreover, the dynamics of the interactome in response to cellular stimuli and across normal physiological contexts remain incompletely understood. This thesis considers the application of a quantitative proteomic approach, protein correlation profiling (PCP), to map the interactome in its native physiological context. I explore computational methods for the analysis of PCP data, and describe their application to infer a dataset of protein-protein interactions from seven mouse tissues. In Chapter 2, I studied the dominant paradigm used to analyze PCP data, which entails the use of supervised machine-learning methods to infer interaction networks from these complex datasets. I found that one widely used strategy needlessly biases network inference towards highly studied proteins and away from novel interactions between functionally un-connected proteins. In Chapter 3, I applied the methods studied in Chapter 2 to a newly collected, in vivo PCP dataset. I used the same machine-learning approach to infer tissue-specific protein-protein interaction networks for seven mouse tissues. I then analyzed these tissue interactome networks to uncover insights about protein function, network evolution, and human disease. Collectively, the work described in this thesis provides a framework to understand the rewiring of the protein-protein interaction network across physiological conditions using PCP.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/78492
note: UNDERSTANDING MAMMALIAN BIOLOGY AND DISEASE THROUGH TISSUE-SPECIFIC PROTEIN-PROTEIN INTERACTION NETWORKS by Michael Skinnider B.ArtsSc., McMaster University, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Genome Science and Technology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) May 2021 © Michael Skinnider, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Understanding mammalian biology and disease through tissue-specific protein-protein interaction networks submitted by Michael Skinnider in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Genome Science and Technology Examining Committee: Dr. Leonard Foster, Professor, Department of Biochemistry & Molecular Biology, UBC Supervisor Dr. Pamela Hoodless, Professor, Department of Medical Genetics, UBC Supervisory Committee Member Dr. Joerg Gsponer, Associate Professor, Department of Biochemistry & Molecular Biology, UBC Supervisory Committee Member Dr. Gabriela Cohen-Freue, Associate Professor, Department of Statistics, UBC University Examiner Dr. Paul Pavlidis, Professor, Department of Psychiatry, UBC University Examiner Additional Supervisory Committee Members: Dr. Sara Mostafavi, Assistant Professor, Department of Medical Genetics, UBC Supervisory Committee Member iii Abstract Biological functions are mediated by the dynamic organization of DNA, RNA, proteins, and other biomolecules in complex networks of interactions. Efforts to chart the network of biologically relevant macromolecular interactions—the “interactome”—therefore occupy a central position in the endeavour to understand the biochemical basis of human physiology, and its perturbation in disease. However, existing interactome maps are incomplete, even for well-studied organisms. Moreover,…
has type: Thesis/Dissertation
date issued: 2021-11
is shown at: 10.14288/1.0398212
language: eng
degree discipline: Genome Science and Technology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Foster, Leonard J.
type: Text
identifier URI: http://hdl.handle.net/2429/78492