title: From gene expression to pathway and transcription factor activities to study chronic liver diseases
creator: Holland, Christian H.
subject: ddc-004
subject: 004 Data processing Computer science
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-570
subject: 570 Life sciences
description: High-throughput techniques such as microarrays and RNA-sequencing enable the relatively easy and inexpensive collection of bulk gene expression profiles from any biological condition. Recently, also the transcriptome of single cells can be efficiently captured via novel single-cell RNA-sequencing technologies. Functional analysis of bulk or single-cell gene expression data has been proven to be a powerful approach as they summarize the large and noisy gene expression space into a smaller number of biologically meaningful features such as pathway and transcription factor activities. In the first part of this thesis, I expanded the scope on the pathway analysis tool PROGENy and the transcription factor analysis tool DoRothEA through thorough benchmarking pipelines. First I transferred their regulatory knowledge from human to mouse to enable the functional characterization of gene expression profiles from mice. Moreover, I demonstrated the robustness and applicability of both tools on human single-cell RNA-sequencing data. In the second part of this thesis, I focussed on the analysis of gene expression profiles from mice and humans in the context of acute and chronic liver diseases. Finally, I identified and functionally characterized exclusively and commonly regulated genes of chronic and acute liver damage in mice and a set of genes that were consistently altered in a novel chronic mouse model and patients of chronic liver disease. Especially the latter demonstrates that, although major interspecies differences remain, there is a common and consistent transcriptomic response to chronic liver damage in mice and humans. This set of genes could be further investigated to study the pathophysiology of the liver in in-vitro and in-vivo studies.
date: 2021
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/30943/1/2021-09-23_Thesis_Christian_Holland_submitted_version.pdf
identifier: DOI:10.11588/heidok.00030943
identifier: urn:nbn:de:bsz:16-heidok-309430
identifier:   Holland, Christian H.  (2021) From gene expression to pathway and transcription factor activities to study chronic liver diseases.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/30943/
rights: info:eu-repo/semantics/openAccess
rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id)
language: eng