eprintid: 30943
rev_number: 20
eprint_status: archive
userid: 6317
dir: disk0/00/03/09/43
datestamp: 2021-12-21 07:30:16
lastmod: 2022-01-13 06:51:00
status_changed: 2021-12-21 07:30:16
type: doctoralThesis
metadata_visibility: show
creators_name: Holland, Christian H.
title: From gene expression to pathway and transcription factor activities to study chronic liver diseases
subjects: ddc-004
subjects: ddc-500
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
cterms_swd: Bioinformatik
cterms_swd: Biomedizin
cterms_swd: Leber
abstract: 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
id_scheme: DOI
id_number: 10.11588/heidok.00030943
ppn_swb: 1785182854
own_urn: urn:nbn:de:bsz:16-heidok-309430
date_accepted: 2021-12-03
advisor: HASH(0x55a9a633da08)
language: eng
bibsort: HOLLANDCHRFROMGENEEX2021
full_text_status: public
place_of_pub: Heidelberg
citation:   Holland, Christian H.  (2021) From gene expression to pathway and transcription factor activities to study chronic liver diseases.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/30943/1/2021-09-23_Thesis_Christian_Holland_submitted_version.pdf