Xiaoxiao Zhang

Cancer is a disease of the genome, with both structural and numerical chromosomal aberrations, so called aneuploidy, occurring concomitantly in most tumors. Despite this co-occurrence, the advances in the characterization of point mutations and structural and numerical changes failed to provide an insight into a possible functional relationship between structural and whole chromosomal instability. Recently, novel evidence suggests that numerical chromosomal aberrations leads to delayed S phase ...

We intend to shed light on the interplay between the regulation of replication origin firing and mitotic chromosome segregation. The relationship between faithful genome replication and chromosome segregation is mutual: de-regulated genome replication causes replication stress and chromosome missegregation [1, 2]. Conversely, chromosome missegregation causes replication stress [3, 4]. Although it is clear that proper regulation of origin firing, the main focus of our lab, is key for complete and ...

To maintain genome stability, human cells depend on accurate DNA replication in S-phase and chromosome segregation in mitosis. Replication stress refers to slowing down or stalling of replication forks that occurs due to DNA lesions, R-loops or oncogene activation. One consequence of replication stress is entry of cells into mitosis with incompletely replicated DNA and thus aberrant mitosis. Phosphorylation of proteins by kinase ATR and its downstream effector CHK1 protects stalled replication ...

The objective of the central project is providing access to state-of-the-art sequencing technology and methods as well as novel next-generation sequencing (NGS)-based approaches to all partners and individual projects within the consortium. Advances in NGS and NGS-based approaches such as whole-genome sequencing (WGS) have tremendously improved the detection of structural variants/copy number variations (CNVs) and single somatic variants and mutations as measures of genome integrity. With ...

Genomic instability is a shared pathogenic mechanism of selected inherited, monogenic disorders caused by mutations in genes encoding proteins with important functions for genomic maintenance. Recent advances in next-generation sequencing (NGS) technologies have allowed the identification of novel genes associated with genomic instability syndromes. However, our understanding of alterations of genomic maintenance in mitotic cells and mechanisms of disease-associated chromosome instability is still ...

Many cancer cells are chromosomally unstable, a phenotype describing a tendency for accumulating chromosomal aberrations. Entire chromosomes tend to be gained or lost, which is called whole chromosome instability (W-CIN). Structural chromosomal instability (S-CIN) describes an increased rate of gaining, losing or translocating smaller parts of chromosomes. Here we analyse data from 33 cancer types to find differences and commonalities between W-CIN and S-CIN. We find, that W-CIN is strongly linked ...

Cancer researchers perform experiments with cell lines to better understand the biology of cancer and to develop new anti-cancer treatments. A prerequisite to translate promising results from these \textit{in vitro} experiments to clinical applications is to use the most appropriate cell line for a given tumour or cancer subtype. We present MFmap (model fidelity map), a deep learning technique to integrate cancer genomic data from patients with cell line data. The MFmap neural network compresses ...

We implemented the pan-cancer chromosomal instability association studies pipeline using R-3.6. The source code and data are available at https://github.com/mcmzxx/pancan_cin

All statistical and machine learning analysis was done with R 3.6.3 and Python 3.6, the source code is available at https://github.com/mcmzxx/mfMap.py.