eprintid: 35696
rev_number: 14
eprint_status: archive
userid: 8594
dir: disk0/00/03/56/96
datestamp: 2024-12-05 13:53:01
lastmod: 2025-01-07 14:25:37
status_changed: 2024-12-05 13:53:01
type: doctoralThesis
metadata_visibility: show
creators_name: Yuan, Zhao
title: Analysis of somatic copy number alterations in liquid biopsies from cancer patients
subjects: ddc-500
subjects: ddc-570
subjects: ddc-610
divisions: i-140001
adv_faculty: af-14
abstract: Compared to tissue biopsies, ctDNA provides a more comprehensive tumor landscape, allowing for repeated non-invasive sampling. Therefore, ctDNA detection has a broad application prospect in tumor diagnosis, treatment and monitoring. However, due to the low content of ctDNA in cfDNA, ctDNA detection requires a high sequencing depth to achieve high sensitivity. Currently, the commonly used ctDNA testing scheme is panel sequencing with high coverage, so that genes of interest can be tested at a lower cost. However, panel sequencing has limited ability to detect other variants such as SV and CNV. Another option is lcWGS. lcWGS is able to identify CNVs, providing valuable insights into genomic alterations. Based on the data of HIPO-K34 and INFORM, this study explored the ability of ctDNA detection by the two schemes. The HIPO-K34 project focused on patients with ALK gene-fused non-small cell lung cancer (NSCLC) and contains multi-time point sequencing data from lcWGS and panel sequencing. The INFORM project consists of liquid biopsy samples and tissue samples taken from the same patient at the same time point. In addition, various detection tools were benchmarked using simulated data with known tumor DNA fractions and CNVs. In order to improve the detection performance, the tools were optimized and the tool with the best performance was selected. Finally, a pipeline combining the panel analysis process with the optimized lcWGS analysis process was established for the accurate analysis of liquid biopsy samples.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00035696
ppn_swb: 1913720861
own_urn: urn:nbn:de:bsz:16-heidok-356965
date_accepted: 2024-11-22
advisor: HASH(0x55e83aff2850)
language: eng
bibsort: YUANZHAOANALYSISOF20241122
full_text_status: public
place_of_pub: Heidelberg
citation:   Yuan, Zhao  (2024) Analysis of somatic copy number alterations in liquid biopsies from cancer patients.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/35696/1/ZhaoYuan_thesis_final.pdf