A5055672359- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- interferon and immune responses
- DNA Repair Mechanisms
- Estrogen and related hormone effects
- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Microbial Metabolic Engineering and Bioproduction
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Advanced Proteomics Techniques and Applications
- Epigenetics and DNA Methylation
- FOXO transcription factor regulation
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- Scientific Computing and Data Management
- PARP inhibition in cancer therapy
- Advanced Data Storage Technologies
The Netherlands Cancer Institute
2021-2025
Oncode Institute
2021-2025
University Medical Center Groningen
2019-2025
Innsbruck Medical University
2025
Universität Innsbruck
2025
University of Groningen
2019-2023
Helmholtz Zentrum München
2019-2023
Cancer Genomics Centre
2021
Laboratoire de Biologie du Développement de Villefranche-sur-Mer
2020
European Bioinformatics Institute
2011-2019
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature cancer. Using this information to guide development and application therapies in clinic is challenging. Here, we report how cancer-driven alterations identified 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, gene expression) can be mapped onto 1,001 molecularly annotated human cell lines correlated with sensitivity 265 drugs. We find...
Aberrant cell signaling can cause cancer and other diseases is a focal point of drug research. A common approach to infer activity pathways from gene expression. However, mapping expression pathway components disregards the effect post-translational modifications, downstream signatures represent very specific experimental conditions. Here we present PROGENy, method that overcomes both limitations by leveraging large compendium publicly available perturbation experiments yield core Pathway...
BioModels (http://www.ebi.ac.uk/biomodels/) is a repository of mathematical models biological processes. A large set curated to verify both correspondence the process that model seeks represent, and reproducibility simulation results as described in corresponding peer-reviewed publication. Many submitted database are annotated, cross-referencing its components external resources such records, terms from controlled vocabularies ontologies. comprises two main branches: one composed derived...
Chromosome instability (CIN) is the most common form of genome and a hallmark cancer. CIN invariably leads to aneuploidy, state karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found aneuploid cells experience DNA replication stress in their first S-phase precipitate continuous This generates repertoire genetically diverse with structural chromosomal abnormalities either continue proliferating or stop dividing. Cycling display lower complexity compared arrested...
Abstract While the effect of amplification-induced oncogene expression in cancer is known, impact copy-number gains on “bystander” genes less understood. We create a comprehensive map dosage compensation by integrating and copy number profiles from over 8000 tumors The Cancer Genome Atlas cell lines Cell Line Encyclopedia. Additionally, we analyze 17 open reading frame screens to identify toxic cells when overexpressed. Combining these approaches, propose class ‘Amplification-Related Gain Of...
Abstract Background Systems biology projects and omics technologies have led to a growing number of biochemical pathway models reconstructions. However, the majority these are still created de novo , based on literature mining manual processing data. Results To increase efficiency model creation, Path2Models project has automatically generated mathematical from representations using suite freely available software. Data sources include KEGG, BioCarta, MetaCyc SABIO-RK. Depending source data,...
Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent origin and typically regulated by differential DNA methylation inherited from gametes. Imprinting pervasive in murine extra-embryonic lineages, uniquely, several has been found conferred non-canonically through maternally repressive histone modification H3K27me3. However, underlying regulatory mechanisms non-canonical post-implantation development remain...
Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal leads to karyotype heterogeneity tumors is associated with therapy resistance, metastasis poor prognosis. It has been hypothesized that aneuploidy per se sufficient drive CIN, however due limited models heterogenous results, it remained controversial which aspects of can CIN. In this study we systematically tested the impact different types aneuploidies on induction We generated a plethora isogenic...
Single-cell open chromatin profiling via scATAC-seq has become a mainstream measurement of in single-cells. Here we present epiAneufinder, an algorithm that exploits the read count information from data to extract genome-wide copy number alterations (CNAs) for individual cells, allowing study CNA heterogeneity sample at single-cell level. Using different cancer datasets, show epiAneufinder can identify intratumor clonal populations single cells based on their profiles. We demonstrate these...
Cells respond to double-strand breaks (DSBs) by activating DNA damage response pathways, including cell cycle arrest. We have previously shown that a single break generated via CRISPR/Cas9 is sufficient delay progression and compromise viability. However, we also found the cellular DSBs can vary, independent of number lesions. This implies not all are equally toxic, raises question if location could influence its toxicity. To systematically investigate DSB-location determinant toxicity...
Chromosomal instability (CIN) and aneuploidy are hallmarks of cancer. As most cancers aneuploid, targeting or CIN may be an effective way to target a broad spectrum cancers. Here, we perform two small molecule compound screens identify drugs that selectively cells aneuploid exhibit phenotype. We find much more sensitive the energy metabolism regulating drug ZLN005 than their euploid counterparts. Furthermore, with ongoing phenotype, induced by spindle assembly checkpoint (SAC) alleviation,...
Faithful and timely repair of DNA double‐strand breaks (DSBs) is fundamental for the maintenance genomic integrity. Here, we demonstrate that meiotic recombination co‐factor MND1 facilitates DSBs in somatic cells. We show localizes to DSBs, where it stimulates through homologous (HR). Importantly, not involved response replication‐associated implying dispensable HR‐mediated one‐ended DSBs. Instead, find specifically plays a role two‐ended are induced by irradiation (IR) or various...
Horseradish peroxidases (HRPs) from Armoracia rusticana have long been utilized as reporters in various diagnostic assays and histochemical stainings. Regardless of their increasing importance the field life sciences suggested uses medical applications, chemical synthesis other industrial HRP isoenzymes, substrate specificities enzymatic properties are poorly characterized. Due to lacking sequence information natural isoenzymes low levels expression heterologous hosts, commercially available...
Abstract Chromosomal instability (CIN) drives the formation of karyotype aberrations in cancer cells and is a major contributor to intra-tumour heterogeneity, metastasis, therapy resistance. Understanding how CIN contributes tumour evolution requires quantification rates primary tumours. Single-cell sequencing-based technologies enable detection however deducing actual that underlie heterogeneity still complicated. We have developed an in-silico model, called CINsim , simulate dynamics...
Abstract Aneuploidy, while detrimental to untransformed cells, is notably prevalent in cancer. Aneuploidy found as an early event during tumorigenesis which indicates that cancer cells have the ability surmount initial stress responses associated with aneuploidy, enabling rapid proliferation despite aberrant karyotypes. To generate more insight into key cellular processes and requirements underlying adaptation we generated a panel of aneuploid clones p53-deficient RPE-1 studied their...
High performance computing (HPC) clusters play a pivotal role in large-scale bioinformatics analysis and modeling. For the statistical language R, packages exist to enable user submit their analyses as jobs on HPC schedulers. However, these do not scale well high numbers of tasks, processing overhead quickly becomes prohibitive bottleneck.Here we present clustermq, an R package that can process up three orders magnitude faster than previously published alternatives. We show this for...
Abstract Aberrant cell signaling is known to cause cancer and many other diseases, as well a focus of treatment. A common approach infer its activity on the level pathways using gene expression. However, mapping expression pathway components disregards effect post-translational modifications, downstream signatures represent very specific experimental conditions. Here we present PROGENy, method that overcomes both limitations by leveraging large compendium publicly available perturbation...
Abstract Chromosomal gains are among the most frequent somatic genetic alterations occurring in cancer. While effect of sustained oncogene expression has been characterized, impact copy-number affecting collaterally-amplified “bystander” genes on cellular fitness remains less understood. To investigate this, we built a comprehensive map dosage compensations across human cancers by integrating and copy number profiles from over 8,000 TCGA tumors CCLE cell lines. Further, analyzed gene...
Abstract Aneuploidy and chromosomal instability are both commonly found in cancer. Chromosomal leads to karyotype heterogeneity tumors is associated with therapy resistance, metastasis poor prognosis. It has been hypothesized that aneuploidy per se sufficient drive CIN, however due limited models heterogenous results, it remained controversial which aspects of can CIN. In this study we systematically tested the impact different types aneuploidies on induction We generated a plethora isogenic...
Abstract Chromosomal instability is a hallmark of cancer, but also an instigator aneuploidy-induced stress, reducing cellular fitness. To better understand how cells with CIN adjust to aneuploidy and adopt malignant fate in vivo , we performed genome-wide mutagenesis screen mice. We find that specifically aneuploid tumors inactivate Stat1 signaling combination increased Myc activity. By contrast, loss p53 common, not enriched tumors. Validation another tissue type confirmed promotes immune...