16 Result(s)
within
Harmen J. G. van de Werken
-
Article
Open AccessRunx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo
Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that s...
-
Article
Open AccessOvercoming immune checkpoint blockade resistance in solid tumors with intermittent ITK inhibition
Cytotoxic CD8 + T cell (CTL) exhaustion is driven by chronic antigen stimulation. Reversing CTL exhaustion with immune checkpoint blockade (ICB) has provided clinical benefits in different types of cancer. We,...
-
Article
Open AccessEvaluation of pre-processing methods for tear fluid proteomics using proximity extension assays
Tear fluid forms a potential source for biomarker identification, and can be minimal invasively collected via Schirmer strips. The lack of knowledge on the processing of Schirmer strips however complicates the...
-
Article
Open AccessFunctional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests
Germline BRCA1/2 mutation status is predictive for response to Poly-[ADP-Ribose]-Polymerase (PARP) inhibitors in breast cancer (BC) patients. However, non-germline BRCA1/2 mutated and homologous recombination rep...
-
Article
Open AccessStratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenoty** and machine learning
Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predi...
-
Article
Open AccessFASTAFS: file system virtualisation of random access compressed FASTA files
The FASTA file format, used to store polymeric sequence data, has become a bioinformatics file standard used for decades. The relatively large files require additional files, beyond the scope of the original f...
-
Article
Open AccessThe genomic landscape of 85 advanced neuroendocrine neoplasms reveals subtype-heterogeneity and potential therapeutic targets
Metastatic and locally-advanced neuroendocrine neoplasms (aNEN) form clinically and genetically heterogeneous malignancies, characterized by distinct prognoses based upon primary tumor localization, functional...
-
Article
Open AccessEvaluation of AXIN1 and AXIN2 as targets of tankyrase inhibition in hepatocellular carcinoma cell lines
AXIN1 mutations are observed in 8–10% of hepatocellular carcinomas (HCCs) and originally were considered to support tumor growth by aberrantly enhancing β-catenin signaling. This view has however been challeng...
-
Article
Open AccessThe genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact
Metastatic castration-resistant prostate cancer (mCRPC) has a highly complex genomic landscape. With the recent development of novel treatments, accurate stratification strategies are needed. Here we present t...
-
Article
The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies
The whole-genome sequencing of prospectively collected tissue biopsies from 442 patients with metastatic breast cancer reveals that, compared to primary breast cancer, tumor mutational burden doubles, the rela...
-
Article
Open AccessMolecular heterogeneity and early metastatic clone selection in testicular germ cell cancer development
Testicular germ cell cancer (TGCC), being the most frequent malignancy in young Caucasian males, is initiated from an embryonic germ cell. This study determines intratumour heterogeneity to unravel tumour prog...
-
Article
Open AccessGene length corrected trimmed mean of M-values (GeTMM) processing of RNA-seq data performs similarly in intersample analyses while improving intrasample comparisons
Current normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and validation of g...
-
Article
Investigation of the spatial structure and interactions of the genome at sub-kilobase-pair resolution using T2C
This protocol describes targeted chromatin capture (T2C), a high-resolution method to interrogate 3D chromatin organization and genomic interactions at sub-kilobase-pair resolution that requires minimal cell n...
-
Article
Open AccessThe detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes
The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function—the storage, expression, and replication of genetic information—is still one of the central i...
-
Article
The lncRNA MIR31HG regulates p16INK4A expression to modulate senescence
Oncogene-induced senescence (OIS) can occur in response to oncogenic insults and is considered an important tumour suppressor mechanism. Here we identify the lncRNA MIR31HG as upregulated in OIS and find that kno...
-
Article
Robust 4C-seq data analysis to screen for regulatory DNA interactions
A high-resolution 4C-seq protocol involving two restriction digests and a revised analysis pipeline allows robust detection of physical interactions between regulatory DNA elements.
