- Statistical Methods in Clinical Trials
- Gene expression and cancer classification
- Statistical Methods and Inference
- Statistical Methods and Bayesian Inference
- MicroRNA in disease regulation
- Bioinformatics and Genomic Networks
- Optimal Experimental Design Methods
- Advanced Statistical Methods and Models
- Genetic Neurodegenerative Diseases
- Cancer-related molecular mechanisms research
- Meta-analysis and systematic reviews
- Functional Brain Connectivity Studies
- Radiomics and Machine Learning in Medical Imaging
- Computational Drug Discovery Methods
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
- Muscle Physiology and Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Machine Learning and Algorithms
- RNA modifications and cancer
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Nonmelanoma Skin Cancer Studies
- SARS-CoV-2 and COVID-19 Research
Leiden University Medical Center
2016-2025
Radboud University Nijmegen
2014-2023
Radboud University Medical Center
2014-2023
John Wiley & Sons (United States)
2022
John Wiley & Sons (United Kingdom)
2022
Oxfam
2022
Leiden University
2004-2021
Vrije Universiteit Amsterdam
2019
Amsterdam Neuroscience
2019
Radboud Institute for Molecular Life Sciences
2016-2017
The heterosexual spread of HIV-1 is occurring at different rates in parts the world. transmission probability per sexual contact low, but may be greatly enhanced by several cofactors. Sexually transmitted diseases (STD), especially genital ulcers, such factors. So far, epidemiological evidence that other STD facilitate weak. objective this study was to determine whether treatable a cohort female prostitutes Kinshasa, Zaire.We conducted nested case-control 431 initially HIV-1-negative women...
This paper presents a global test to be used for the analysis of microarray data. Using this it can determined whether expression pattern group genes is significantly related some clinical outcome interest. Groups may any size from single gene all on chip (e.g. known pathways, specific areas genome or clusters cluster analysis).The allows groups different compared, because gives one p-value group, not each gene. Researchers use investigate hypotheses based theory past research mine ontology...
Abstract Motivation: Many statistical tests have been proposed in recent years for analyzing gene expression data terms of sets, usually from Gene Ontology. These methods are based on widely different methodological assumptions. Some approaches test differential each set against the rest genes, whereas others its own. Also, some a model which genes sampling units, treat subjects as units. This article aims to clarify assumptions behind and indicate preferential methodology testing. Results:...
Abstract This article presents a novel algorithm that efficiently computes L 1 penalized (lasso) estimates of parameters in high‐dimensional models. The lasso has the property it simultaneously performs variable selection and shrinkage, which makes very useful for finding interpretable prediction rules data. new is based on combination gradient ascent optimization with Newton–Raphson algorithm. It described general likelihood function can be applied generalized linear models other an...
Abstract Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on genome-scale analysis differential whole blood after periconceptional exposure to famine during Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by...
This paper presents an overview of the current state art in multiple testing genomics data from a user's perspective. We describe methods for familywise error control, false discovery rate control and proportion estimation confidence, both conceptually practically, explain when to use which type rate. elaborate on assumptions underlying discuss pitfalls interpretation results. In our discussion, we take into account exploratory nature experiments, looking at selection genes before or after...
Abstract Background DNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due differences study design and focus there still is no consensus the annotation of regions predominantly involved tissue-specific methylation. We used new algorithm identify annotate differentially methylated (tDMRs) from Illumina 450k chip data for four peripheral (blood, saliva, buccal swabs...
Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract infection in infants. Only proportion children infected with RSV require hospitalization. Because known risk factors for disease, such as premature birth, cannot fully explain differences disease severity, genetic have been implicated.To study the complexity susceptibility and to identify genes biological pathways involved its development, we performed association involving 470 hospitalized bronchiolitis,...
Summary As the dimensionality of alternative hypothesis increases, power classical tests tends to diminish quite rapidly. This is especially true for high dimensional data in which there are more parameters than observations. We discuss a score test on hyperparameter an empirical Bayesian model as tests. It gives general statistic can be used point null against alternative, even when number exceeds samples. will shown have optimal average neighbourhood hypothesis, makes it proper...
Scatterplots of microarray data generally contain a very large number dots, making it difficult to get good impression their distribution in dense areas.We present fast and simple algorithm for two-dimensional histogram smoothing, visually enhance scatterplots.Functions Matlab R are available from the corresponding author.
Objective Identify gene expression profiles associated with OA processes in articular cartilage and determine pathways changing during the disease process. Methods Genome wide was determined paired samples of affected preserved same joint using microarray analysis for 33 patients RAAK study. Results were replicated independent by RT-qPCR immunohistochemistry. Profiles analyzed online tools DAVID STRING to identify enrichment specific protein-protein interactions. Among 1717 genes that...
The choice for a polyadenylation site determines the length of 3′-untranslated region (3′-UTRs) an mRNA. Inclusion or exclusion regulatory sequences in 3′-UTR may ultimately affect gene expression levels. Poly(A) binding protein nuclear 1 (PABPN1) is involved pre-mRNAs. An alanine repeat expansion PABPN1 (exp-PABPN1) causes oculopharyngeal muscular dystrophy (OPMD). We hypothesized that previously observed disturbed patterns OPMD muscles have been result effect on alternative...
Facioscapulohumeral muscular dystrophy (FSHD: MIM#158900) is a common myopathy with marked but largely unexplained clinical inter- and intra-familial variability. It caused by contractions of the D4Z4 repeat array on chromosome 4 to 1–10 units (FSHD1), or mutations in D4Z4-binding chromatin modifier SMCHD1 (FSHD2). Both situations lead partial opening structure transcription D4Z4-encoded polyadenylated DUX4 mRNA muscle. We measured CpG methylation control, FSHD1 FSHD2 individuals found...
The small size of RNA virus genomes (2-to-32 kb) has been attributed to high mutation rates during replication, which is thought lack proof-reading. This paradigm being revisited owing the discovery a 3'-to-5' exoribonuclease (ExoN) in nidoviruses, monophyletic group positive-stranded viruses with conserved genome architecture. ExoN, homolog canonical DNA proof-reading enzymes, exclusively encoded by nidoviruses larger than 20 kb. All other known non-segmented have smaller genomes. Here we...
In genome-wide association studies (GWAS) of complex traits, single SNP analysis is still the most applied approach. However, identified SNPs have small effects and provide limited biological insight. A more appropriate approach to interpret GWAS data traits analyze combined effect a set grouped per pathway or gene region. We used this study joint on human longevity genetic variation in two candidate pathways, insulin/insulin-like growth factor (IGF-1) signaling (IIS) telomere maintenance...
MicroRNAs (miRNAs), non-coding RNAs regulating gene expression, are frequently aberrantly expressed in human cancers. Next-generation deep sequencing technology enables genome-wide expression profiling of known miRNAs and discovery novel at unprecedented quantitative qualitative accuracy. Deep was performed on 11 fresh frozen clear cell renal carcinoma (ccRCC) adjacent non-tumoral cortex (NRC) pairs, additional ccRCC tissues, 2 lines (n = 35). The 22 ccRCCs patients belonged to 3 prognostic...