Eric-Wubbo Lameijer
A5047891732- Genetic Associations and Epidemiology
- Genomics and Phylogenetic Studies
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Chemical Synthesis and Analysis
- Cancer Genomics and Diagnostics
- Receptor Mechanisms and Signaling
- Genomics and Rare Diseases
- Nutrition, Genetics, and Disease
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genetic Mapping and Diversity in Plants and Animals
- Genetics, Bioinformatics, and Biomedical Research
- Genetic diversity and population structure
- Evolution and Genetic Dynamics
- Mass Spectrometry Techniques and Applications
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Machine Learning in Healthcare
- Genetics, Aging, and Longevity in Model Organisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- Gene Regulatory Network Analysis
- Genomic variations and chromosomal abnormalities
- Microbial Metabolic Engineering and Bioproduction
Leiden University Medical Center
2012-2019
Leiden University
2005-2016
Xi'an Jiaotong University
2016
University Medical Center Groningen
2016
University of Groningen
2016
Wellcome Sanger Institute
2012
Netherlands Consortium for Healthy Ageing
2012
Centre for Human Drug Research
2006
Small insertions and deletions (indels) large structural variations (SVs) are major contributors to human genetic diversity disease. However, mutation rates characteristics of de novo indels SVs in the general population have remained largely unexplored. We report 332 validated changes identified whole genomes 250 families, including complex indels, retrotransposon insertions, interchromosomal events. These data indicate a rate 2.94 (1–20 bp) 0.16 (>20 per generation. De affect on average...
Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection. However, it is not known whether affect fitness independently, so that cumulative loss depends exponentially on number alleles, or synergistically, each additional allele results in a larger decrease relative fitness. with synergistic epistasis should produce negative linkage disequilibrium between and, therefore, an underdispersed...
Abstract Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority studies provide neither global view full spectrum these variants nor integrate them into reference panels genetic variation. Here, we analyse whole genome sequencing data 769 individuals from 250 Dutch families, haplotype-resolved map 1.9 million across 9 different variant classes, including novel forms complex indels,...
Abstract Many disciplines, from human genetics and oncology to plant breeding, microbiology virology, commonly face the challenge of analyzing rapidly increasing numbers genomes. In case Homo sapiens , number sequenced genomes will approach hundreds thousands in next few years. Simply scaling up established bioinformatics pipelines not be sufficient for leveraging full potential such rich genomic datasets. Instead, novel, qualitatively different computational methods paradigms are needed. We...
We developed a software tool to design drug-like molecules, the "Molecule Evoluator", which we introduce and describe here. An atom-based evolutionary approach was used allowing both several types of mutation crossover occur. The novelty, claim, is unprecedented interactive evolution, in user acts as fitness function. This brings human being's creativity, implicit knowledge, imagination into process, next more standard chemical rules. Proof-of-concept demonstrated number ways,...
It has been postulated that aging is the consequence of an accelerated accumulation somatic DNA mutations and subsequent errors in primary structure proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations detecting changes lack insight about minimum level erroneous cause error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced whole genome blood two pairs monozygotic (MZ) twins, 40 100 years old, by...
Nowadays millions of different compounds are known, their structures stored in electronic databases. Analysis these data could yield valuable insights into the laws chemistry and habits chemists. We have therefore explored public database National Cancer Institute (>250,000 compounds) by pattern searching. split molecules this fragments to find out which exist, how frequent they are, whether occurrence one fragment a molecule is related another, nonoverlapping fragment. It turns that some...
Abstract Motivation: RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used cellular phenotyping and help establishing etiology diseases characterized by abnormal splicing patterns. In RNA-Seq, exact nature events buried in reads span exon–exon boundaries. The accurate efficient mapping these to reference genome major challenge. Results: We developed PASSion, pattern growth algorithm-based pipeline splice site...
Residues in the transmembrane region of G protein-coupled receptors (GPCRs) are important for ligand binding and activation, but function individual positions is poorly understood. Using a sequence alignment class A GPCRs (grouped subfamilies), we propose so-called "two-entropies analysis" to determine potential role GPCRs. In our approach, such appear scattered, while largely clustered according their biological function. Our method appears superior when compared other bioinformatics...
Abstract Telomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary environmental factors regulating TL are currently widely investigated, however, their relative contribution to variability still understudied. We have used whole genome sequencing data of 250 family trios from the Genome Netherlands project perform computational measurement a series regression genome-wide association analyses reveal inheritance patterns...
We used a new software tool for de novo design, the "Molecule Evoluator", to generate number of small molecules. Explicit constraints were relatively low molecular weight and otherwise limited functionality, example, numbers hydrogen bond donors acceptors, one or two aromatic rings, rotatable bonds. In this way, we obtained collection scaffold- templatelike molecules rather than fully "decorated" ones. asked medicinal chemists evaluate suggested ease synthesis overall appeal, allowing them...
Abstract Structural variation (SV) represents a major source of differences between individual human genomes and has been linked to disease phenotypes. However, the majority studies provide neither global view full spectrum these variants nor integrate them into reference panels genetic variation. Here, we analyse whole genome sequencing data 769 individuals from 250 Dutch families, haplotype-resolved map 1.9 million across 9 different variant classes, including novel forms complex indels,...
To help chemists design new drugs, we created a tool that uses interactive evolution to drug molecules, the "Molecule Evoluator". In contrast most other evolutionary de novo programs, molecule representation and set of mutations enable it both search chemical space all like molecules extensively fine-tune molecular structures problem at hand. Additionally, use interaction with user as fitness function, which is in algorithms design. This interactivity allows Molecule Evoluator domain...