A5023194460- Cancer Genomics and Diagnostics
- Aortic aneurysm repair treatments
- Cardiac, Anesthesia and Surgical Outcomes
- Aortic Disease and Treatment Approaches
- Genomics and Rare Diseases
- Genetic factors in colorectal cancer
- Nonlinear Dynamics and Pattern Formation
- Genomic variations and chromosomal abnormalities
- Vascular Procedures and Complications
- Hemodynamic Monitoring and Therapy
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Molecular Biology Techniques and Applications
- Advanced Thermodynamics and Statistical Mechanics
- Cerebrovascular and Carotid Artery Diseases
- DNA Repair Mechanisms
- Infectious Aortic and Vascular Conditions
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Fatty Acid Research and Health
- Mathematical and Theoretical Epidemiology and Ecology Models
- Central Venous Catheters and Hemodialysis
VieCuri Medisch Centrum
2018-2025
Maastricht University
2024
Radboud University Nijmegen
2024
Radboud University Medical Center
2024
University Medical Center
2024
Maastricht University Medical Centre
2024
Ziekenhuis Groep Twente
2024
University Medical Center Groningen
2022
University Medical Center Utrecht
2016-2021
Oncode Institute
2017-2021
Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such can be distinguished by various characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, genomic distribution association with (epi)-genomic features. We created MutationalPatterns, an R/Bioconductor package allows researchers to characterize broad range patterns base dissect the underlying molecular mechanisms. Furthermore, it...
5-Fluorouracil (5-FU) is a chemotherapeutic drug commonly used for the treatment of solid cancers. It proposed that 5-FU interferes with nucleotide synthesis and incorporates into DNA, which may have mutational impact on both surviving tumor healthy cells. Here, we treat intestinal organoids find highly characteristic pattern dominated by T>G substitutions in CTT context. Tumor whole genome sequencing data confirms this signature also identified vivo colorectal breast cancer patients who...
Abstract GRIDSS2 is the first structural variant caller to explicitly report single breakends—breakpoints in which only one side can be unambiguously determined. By treating breakends as a fundamental genomic rearrangement signal on par with breakpoints, explain 47% of somatic centromere copy number changes using non-centromere sequence. On cohort 3782 deeply sequenced metastatic cancers, achieves an unprecedented 3.1% false negative rate and 3.3% discovery identifies novel 32–100 bp...
Abstract Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells regenerative medicine. To assess genetic risks induced by culturing, we determined all mutations individual human whole genome sequencing. Individual pluripotent, intestinal, and liver accumulate 3.5 ± 0.5, 7.2 1.1 8.3 3.6 base substitutions per population doubling, respectively. The annual mutation accumulation rate adult is nearly 40-fold higher than vivo rate. Mutational...
Nucleotide excision repair (NER) is one of the main DNA pathways that protect cells against genomic damage. Disruption this pathway can contribute to development cancer and accelerate aging. Mutational characteristics NER-deficiency may reveal important diagnostic opportunities, as tumors deficient in NER are more sensitive certain treatments. Here, we analyzed genome-wide somatic mutational profiles adult stem (ASCs) from NER-deficient Ercc1-/Δ mice. Our results indicate increases base...
Biological, clinical, and pharmacological research now often involves analyses of genomes, transcriptomes, proteomes, interactomes, within between individuals across species. Due to large volumes, the analysis integration data generated by such high-throughput technologies have become computationally intensive, can no longer happen on a typical desktop computer.In this chapter we show how describe execute same using number workflow systems these follow different approaches tackle execution...
Abstract Here, we describe a novel approach for rapid discovery of set tumor-specific genomic structural variants (SVs), based on combination low coverage cancer genome sequencing using Oxford Nanopore with an SV calling and filtering pipeline. We applied the method to tumor samples high-grade ovarian prostate patients validated average ten somatic SVs per patient breakpoint-spanning PCR mini-amplicons. These could be quantified in ctDNA metastatic digital assay. The results suggest that...
Genomic structural variants (SVs) can affect many genes and regulatory elements. Therefore, the molecular mechanisms driving phenotypes of patients carrying de novo SVs are frequently unknown. We applied a combination systematic experimental bioinformatic methods to improve diagnosis 39 with multiple congenital abnormalities and/or intellectual disability harboring apparent SVs, most an inconclusive after regular genetic testing. In 7 these cases (18%), whole-genome sequencing analysis...
Abstract GRIDSS2 is the first structural variant caller to explicitly report single breakends - breakpoints in which only one side can be unambiguously determined. By treating as a fundamental genomic rearrangement signal on par with breakpoints, explain 47% of somatic centromeric copy number changes using non-centromeric sequence, chromosome 1 exhibiting unique signature. On cohort 3,782 deeply sequenced metastatic cancers, achieved an unprecedented 3.1% false negative rate and identified...
Abstract Inflammatory liver disease increases the risk of developing primary cancer. The mechanism through which induces tumorigenesis remains unclear, but is thought to occur via increased mutagenesis. Here, we performed whole-genome sequencing on clonally expanded single stem cells cultured as intrahepatic cholangiocyte organoids (ICOs) from patients with alcoholic cirrhosis, non-alcoholic steatohepatitis (NASH), and sclerosing cholangitis (PSC). Surprisingly, find that these precancerous...
Introduction: Peripherally inserted central catheters are venous devices intended for short to medium periods of intravenous treatment. Positioning the catheter tip at cavoatrial junction is necessary optimum performance a peripherally catheter. In this study, safety, effectiveness and cost-effectiveness electrocardiographic-guided positioning in Dutch teaching hospital were evaluated. Methods: All patients who received 2016 using electrocardiographic guidance compared those where...
<h3>Importance</h3> Triplet chemotherapy with fluorouracil, folinic acid, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-B) is an effective first-line treatment option for patients metastatic colorectal cancer (mCRC). However, the degree of implementation FOLFOXIRI-B in daily practice unknown. <h3>Objectives</h3> To evaluate current adoption rate mCRC investigate perspectives medical oncologists toward this option. <h3>Design, Setting, Participants</h3> This 1-week, multicenter,...
The aim of this work was to explore the physiological and perceptual limits exercise in children with varying degrees motor impairment, relationships measures health.In a group comparison design, 35 boys aged 12-15 years completed Movement ABC test for assessment followed by an incremental cycle ergometer exhaustion maximal oxygen uptake (VO2peak), respiratory exchange ratio (RER), heart rate (HR) rating perceived exertion (RPE). Ten participants classified as having either high or no...
Abstract Base substitution catalogs represent historical records of mutational processes that have been active in a system. Such can be distinguished by typical characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, distribution throughout the genome. MutationalPatterns is an R/Bioconductor package characterizes this broad range patterns potential relations with (epi-)genomic features. Furthermore, it offers efficient method to quantify...
Abstract 5-Fluorouracil (5-FU) is a chemotherapeutic drug component that commonly used for the treatment of solid cancers. It proposed 5-FU possesses anticancer properties via interference with nucleotide synthesis and incorporation into DNA. As both mechanisms may have mutational impact on surviving tumor healthy cells, we treated intestinal organoids followed by whole genome sequencing analysis uncovered highly characteristic pattern dominated T>G substitutions in CTT context. Analysis...
Objective The choice between a resynchronization pacemaker (CRT-P) or defibrillator (CRT-D) is still matter of debate. We hypothesised that when selecting patients based on co-morbidities and age as proposed by the ESC-guidelines, there would be no long-term survival benefit CRT-D compared to CRT-P.Methods performed retrospective analysis who received CRT device at University Hospitals Leuven 2001 2007. For association predictors outcome, uni- multivariate Cox regression analyses were...
Abstract Genetic changes acquired during in vitro culture pose a potential risk for the successful application of stem cells regenerative medicine. To assess mutation accumulation risks induced by culturing, we determined genetic aberrations individual human pluripotent (iPS cells) and adult (ASCs) whole genome sequencing analyses. Individual iPS cells, intestinal ASCs liver accumulated 3.5±0.5, 7.2±1.0 8.4±3.6 base substitutions per population doubling, respectively. The annual rate adds up...
ABSTRACT Nucleotide excision repair (NER) is one of the main DNA pathways that protect cells against genomic damage. Disruption this pathway can contribute to development cancer and accelerate aging. Tumors deficient in NER are more sensitive cisplatin treatment. Characterization mutational consequences NER-deficiency may therefore provide important diagnostic opportunities. Here, we analyzed somatic profiles adult stem (ASCs) from NER-deficient Ercc1 -/Δ mice, using whole-genome sequencing...
Results of a numerical analysis set one-dimensional reaction -diffusion equations are presented. The basis these is model scheme chemical reactions, involving auto-and cross-catalytic steps (“Brusselator”). steady state problem solved numerically, fully exploiting the properties recently developed continuation codes. Bifurcation diagrams constructed for zero flux boundary conditions. For relatively large diffusivity initial species Brusselator displays huge number dissipative structures. At...
Dysautonomia is a disruption of the body's autonomic processes. Symptoms vary among patients, depending on underlying disease pathways. Given that symptoms can affect all organ functions, dysautonomia often significantly impacts quality life. However, due to its complex and varied presentation, early recognition remains challenge, yet it crucial for improving patient outcomes. We report case with KRIT1 mutation presenting causing urological, sexual, bowel dysfunction. hypothesize patient's...