Holger Schwender

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

Are you Holger Schwender?

Claim your profile

Publications (79)205.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the effects of cannabis on the ability required to ride a bicycle, repetitive practical cycling tests and medical examinations were carried out before and after inhalative consumption of cannabis. A maximum of three joints with body weight-adapted THC content (300 μg THC per kg body weight) could be consumed by each test subject. Fourteen regular cannabis-consuming test subjects were studied (12 males, 2 females). In summary, only a few driving faults were observed even under the influence of very high THC concentrations. A defined THC concentration that leads to an inability to ride a bicycle cannot be presented. The test subjects showed only slight distinctive features that can be documented using a medical test routinely run for persons under suspicion of driving under the influence of alcohol or drugs.
    No preview · Article · Jan 2016 · Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Most comparisons of blood alcohol concentrations (BAC) and breath alcohol concentrations (BrAC) are either derived from drinking trials with rigid drinking protocols or from investigative authorities' data with considerable time differences between the determination of BAC and BrAC. In general, only comparisons of relatively low BAC-BrAC pairs are available. Therefore, the relationship between BAC and BrAC was examined even for high BAC above 2g/kg. The results of a large-scale drinking test under realistic conditions with 78 test persons and short time intervals between BAC and BrAC measurements are presented. It was shown that the conversion factor Q varies greatly (between 1571:1 and 2394:1) and increases with increasing BAC. A constant conversion factor that is suitable for variable forensic purposes could not be presented.
    No preview · Article · Nov 2015 · Forensic science international

  • No preview · Conference Paper · Nov 2015

  • No preview · Conference Paper · Nov 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We performed a systematic analysis of gene expression features in early (10-21 days) development of human vs mouse embryonic cells (hESCs vs mESCs). Many development features were found to be conserved, and a majority of differentially regulated genes have similar expression change in both organisms. The similarity is especially evident, when gene expression profiles are clustered together and properties of clustered groups of genes are compared. First 10 days of mESC development match the features of hESC development within 21 days, in accordance with the differences in population doubling time in human and mouse ESCs. At the same time, several important differences are seen. There is a clear difference in initial expression change of transcription factors and stimulus responsive genes, which may be caused by the difference in experimental procedures. However, we also found that some biological processes develop differently; this can clearly be shown, for example, for neuron and sensory organ development. Some groups of genes show peaks of the expression levels during the development and these peaks cannot be claimed to happen at the same time points in the two organisms, as well as for the same groups of (orthologous) genes. We also detected a larger number of upregulated genes during development of mESCs as compared to hESCs. The differences were quantified by comparing promoters of related genes. Most of gene groups behave similarly and have similar transcription factor (TF) binding sites on their promoters. A few groups of genes have similar promoters, but are expressed differently in two species. Interestingly, there are groups of genes expressed similarly, although they have different promoters, which can be shown by comparing their TF binding sites. Namely, a large group of similarly expressed cell cycle-related genes is found to have discrepant TF binding properties in mouse vs human.
    Preview · Article · Oct 2015 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The forkhead box F2 gene (FOXF2) located in chromosome 6p25.3 has been shown to play a crucial role in palatal development in mouse and rat models. To date, no evidence of linkage or association has been reported for this gene in humans with oral clefts.METHODS Allelic transmission disequilibrium tests were used to robustly assess evidence of linkage and association with nonsyndromic cleft lip with or without cleft palate for nine single nucleotide polymorphisms (SNPs) in and around FOXF2 in both Asian and European trios using PLINK.RESULTSStatistically significant evidence of linkage and association was shown for two SNPs (rs1711968 and rs732835) in 216 Asian trios where the empiric P values with permutation tests were 0.0016 and 0.005, respectively. The corresponding estimated odds ratios for carrying the minor allele at these SNPs were 2.05 (95% confidence interval = 1.41, 2.98) and 1.77 (95% confidence interval = 1.26, 2.49), respectively.CONCLUSION Our results provided statistical evidence of linkage and association between FOXF2 and nonsyndromic cleft lip with or without cleft palate. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · Birth Defects Research Part A Clinical and Molecular Teratology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A new Bayesian approach for quantifying spatial clustering is proposed that employs a mixture of gamma distributions to model the squared distance of points to their second nearest neighbors. The method is designed to answer questions arising in biophysical research on nanoclusters of Ras proteins. It takes into account the presence of disturbing metacluster structures as well as non-clustering objects, both common among Ras clusters. Its focus lies on estimating the proportion of points lying in clusters, the mean cluster size and the mean cluster radius without depending on prior knowledge of the parameters. The performance of the model compared to other cluster methods is demonstrated in a comprehensive simulation study, employing a specific new class of spatial point processes, the double Matérn cluster process. Further results and arguments as well as data and code are available as supplementary material.
    Full-text · Article · Jul 2015 · Computational Statistics & Data Analysis
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effects of alcohol on the ability to ride a bicycle, practical cycling tests were carried out at different blood alcohol concentrations (BAC). For this purpose, various alcoholic beverages could be consumed from around 2 p.m. until 11 p.m. Afterwards, the test persons spent the night on the trial site and were provided with dormitory sleeping accommodation. On the following morning, beginning at around 8 a.m., a final cycling test was performed. The performances of those test persons who had returned to state of soberness and of those with residual blood alcohol levels were compared to the performances on the day before. The practical ability to ride a bicycle was significantly reduced in the postalcoholic state compared to the rides of the day before. The relative cycling performance in the postalcoholic state was comparable to the rides under the influence of BAC of around 0.30 g/kg. There were no remarkable differences between the groups with and without residual blood alcohol levels regarding the rides on the next morning. Therefore, it can be assumed that the direct influence of residual blood alcohol levels plays a minor role for the ability to ride a bicycle in the postalcoholic state. Instead, the side effects of the high amounts of alcohol that were consumed the night before are crucial.
    No preview · Article · May 2015 · Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin
  • [Show abstract] [Hide abstract]
    ABSTRACT: To examine the effects of alcohol regarding the fitness required to ride a bicycle, practical cycling tests, accompanied by medical examinations, were carried out at different blood alcohol concentrations. Seventy-eight persons were included in the trials (41 males, 37 females). Eighty-three evaluable trials were obtained. Men committed less coordinative driving faults with comparable blood alcohol concentrations. Single highly alcoholized men were able to safely ride their bicycle; however, each of the female test persons had at least one severe driving fault at blood alcohol levels above 1.43 g/kg. Women tended to exhibit signs of alcoholization in the medical examination reports earlier than men.
    No preview · Article · Apr 2015 · Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin
  • [Show abstract] [Hide abstract]
    ABSTRACT: DNA copy number variants play an important part in the development of common birth defects such as oral clefts. Individual patients with multiple birth defects (including oral clefts) have been shown to carry small and large chromosomal deletions. We investigated the role of polymorphic copy number deletions by comparing transmission rates of deletions from parents to offspring in case-parent trios of European ancestry ascertained through a cleft proband with trios ascertained through a normal offspring. DNA copy numbers in trios were called using the joint hidden Markov model in the freely available PennCNV software. All statistical analyses were performed using Bioconductor tools in the open source environment R. We identified a 67 kb region in the gene MGAM on chromosome 7q34, and a 206 kb region overlapping genes ADAM3A and ADAM5 on chromosome 8p11, where deletions are more frequently transmitted to cleft offspring than control offspring. These genes or nearby regulatory elements may be involved in the etiology of oral clefts. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Mar 2015 · Birth Defects Research Part A Clinical and Molecular Teratology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The porphyrias are a group of inherited metabolic diseases resulting from enzymatic deficiencies of specific haem biosynthetic enzymes. They can be classified as primarily acute and non-acute types. Clinically, the acute hepatic porphyrias (AHPs) are characterised by acute neurovisceral attacks. Patients with AHP may be at increased risk for development of hepatocellular carcinoma (HCC). However, systematic studies on the occurrence of other malignancies in patients with the AHPs have not been performed to date. Here, we studied the development of HCC and distinct malignant tumours in patients with the AHPs registered in a single European porphyria specialist centre. A questionnaire was designed and sent to all individuals (n = 122) diagnosed between 1970 and 2012 of whom a valid address was available (n = 82), requesting information on their personal and family history of cancer. Statistical analysis was performed to calculate incidence, prevalence and relative risk of HCC. To calculate confidence intervals, a Poisson distribution was assumed. Forty-nine patients (59.8%) returned a completed questionnaire. Overall, HCC was diagnosed in one female (2.1%), and the remaining patients reported on six distinct malignancies. We were able to confirm that HCC is an important complication in AHP. The patients in our cohort had an approximately 35-fold increased risk of developing HCC, similar to observations in other European countries. In addition, we detected colon, breast, uterine and thyroid cancer as well as lymphoma and a liver metastasis in patients with AHP. However, considering the small number of tumours and patients studied here, the data should be interpreted with caution, and further studies on cancer occurrence in AHP patients will require a multicentre setting.
    No preview · Article · Feb 2015
  • Source
    Wolfgang Kaisers · Heiner Schaal · Holger Schwender
    [Show abstract] [Hide abstract]
    ABSTRACT: The open source environment R is the most widely used software to statistically explore biological data sets including sequence alignments. BAM is the de facto standard file format for sequence alignment. With rbamtools, we provide now a full spectrum of accessibility to BAM for R users such as reading, writing, extraction of subsets and plotting of alignment depth where the script syntax closely follows the SAM/BAM format. Additionally, rbamtools enables fast accumulative tabulation of splicing events over multiple BAM files. rbamtools is available on CRAN and on R-Forge. kaisers@med.uni-duesseldorf.de SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online. © The Author(s) 2015. Published by Oxford University Press.
    Preview · Article · Jan 2015 · Bioinformatics
  • [Show abstract] [Hide abstract]
    ABSTRACT: We examined the relationship between the blood alcohol concentration (BAC) and the fitness to ride a bicycle. One of the aims of the study was to improve the knowledge about the effects of alcohol (at different BAC) on cycling performance.
    No preview · Article · Jan 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To determine the threshold for the absolute inability to ride a bicycle, practical cycling tests and medical examinations at different blood alcohol concentrations were performed. Special attention was given to additional medical examinations, reaction tests and alcohol consumption under real-life conditions. Seventy-eight test subjects were included in the trials (37 females, 41 males). Five test subjects participated twice; thus, there were a total of 83 evaluable trials. Alcohol-related deficits were already identifiable at very low BACs. A significant increase in gross motoric disturbances compared to the soberness state did not regularly occur until a BAC of at least 0.8 g/kg was reached. At the BAC of 1.4 g/kg and above, no test subjects were able to achieve or surpass their sober driving results. Isolated highly alcoholised test subjects rode the bike in a manner that was not conspicuously different than the other sober test persons. Contrary to the assumptions of current German legal practise, it cannot be stated that all people are 'absolutely impaired' to the point of being incapable of riding bicycle at BACs of at least 1.6 g/kg.
    Preview · Article · Nov 2014 · Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin
  • [Show abstract] [Hide abstract]
    ABSTRACT: Case-parent trio studies considering genotype data from children affected by a disease and their parents are frequently used to detect single nucleotide polymorphisms (SNPs) associated with disease. The most popular statistical tests for this study design are transmission/disequilibrium tests (TDTs). Several types of these tests have been developed, for example, procedures based on alleles or genotypes. Therefore, it is of great interest to examine which of these tests have the highest statistical power to detect SNPs associated with disease. Comparisons of the allelic and the genotypic TDT for individual SNPs have so far been conducted based on simulation studies, since the test statistic of the genotypic TDT was determined numerically. Recently, however, it has been shown that this test statistic can be presented in closed form. In this article, we employ this analytic solution to derive equations for calculating the statistical power and the required sample size for different types of the genotypic TDT. The power of this test is then compared with the one of the corresponding score test assuming the same mode of inheritance as well as the allelic TDT based on a multiplicative mode of inheritance, which is equivalent to the score test assuming an additive mode of inheritance. This is, thus, the first time the power of these tests are compared based on equations, yielding instant results and omitting the need for time-consuming simulation studies. This comparison reveals that these tests have almost the same power, with the score test being slightly more powerful.
    No preview · Article · Nov 2014 · Biometrical Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.
    Full-text · Article · Oct 2014 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Case-parent trio studies are commonly employed in genetics to detect variants underlying common complex disease risk. Both commercial and freely available software suites for genetic data analysis usually contain methods for case-parent trio designs. A user might, however, experience limitations with these packages, which can include missing functionality to extend the software if a desired analysis has not been implemented, and the inability to programmatically capture all the software versions used for low-level processing and high-level inference of genomic data, a critical consideration in particular for high-throughput experiments. Here, we present a software vignette (i.e., a manual with step by step instructions and examples to demonstrate software functionality) for reproducible genome-wide analyses of case-parent trio data using the open source Bioconductor package trio. The workflow for the practitioner uses data from previous genetic trio studies to illustrate functions for marginal association tests, assessment of parent-of-origin effects, power and sample size calculations, and functions to detect gene–gene and gene–environment interactions associated with disease.
    No preview · Article · Jul 2014 · Genetic Epidemiology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Urothelial carcinoma (UC) is characterized by multiple recurrent chromosomal changes on a background of increasing genomic instability. To define target genes of recurrent deletions and amplifications, we explored which gene alterations are common in UC, in two recently established cell lines, BC44 and BC61. Materials and methods: Genes located in regions of gain or deletion in the cell lines were identified by array comparative genomic hybridization (aCGH). Six published microarray datasets were analyzed for genes differentially expressed between urothelial tumor vs. normal tissues. Gene expression and chromosomal changes were compared in BC61 cells. Results: The cell lines share homozygous deletions at 9p21 around CDKN2A and amplifications at 11q13.2 around CCND1. In both cell lines 11 genes were commonly lost and 115 gained. Across UC in general, 230 genes were expressed stronger and 349 weaker; a subset displaying corresponding genetic changes in the cell lines. The commonly affected subset contains well-investigated genes like E2F1 and CCNE1, but also several genes not yet sufficiently investigated in UC. Discussion: Our approach highlights genes involved in cell cycle regulation, apoptosis and signal transduction as commonly deregulated across UC. Nevertheless, many chromosomal regions undergoing recurrent changes harbor several commonly deregulated genes that may act jointly in UC development and progression.
    No preview · Article · Jun 2014 · Cancer genomics & proteomics
  • Source

    Full-text · Dataset · May 2014
  • Source
    Wolfgang Kaisers · Holger Schwender · Heiner Schaal
    [Show abstract] [Hide abstract]
    ABSTRACT: Batch effects are artificial sources of variation due to experimental design. Batch effect is a widespread phenomenon in high througput data which can be minimized but not always be avoided. Therefore mechanisms for detection of batch effects are needed which requires comparison of multiple samples. Due to large data volumes 1e12 Bytes this can be technical challenging. We describe the application of hierarchical clustering (HC) on DNA k-mer profiles of multiple fastq files which creates tree structures based on similarity of sequence content. Ideally, HC tree adjacency reflects experimental treatment groups but the algorithm may also agglomerate according to sample preparation groups which then indicates the presence of batch effects. This introduces a new perspective in quality control. In order to perform fast analysis on large data sets we implemented a new algorithm. The algorithm and user interface are implemented a new R-package (seqTools). The result is now available on R-Forge for Linux and Windows. Using this implementation, we compared the transcriptome sequence content of 83 human tissue samples on 13 different flowcells. We pairwise compared flowcells where samples from the same tissue type (fibroblasts or jurkat cells) were present and <10% of the Phred scores were <10. Flowcell based clustering could be identified in 24 of 41 compaired flowcells. The effect predominantly appears on Phred quality deficient flowcells but can also be found between high quality samples. The identified batch effects appear amplified in aligned reads and attenuated in unmapped (i.e. discarded during alignment) reads. Filtering reads for high quality (Phred >30) does not remove the identified batch effects.
    Full-text · Article · May 2014

Publication Stats

885 Citations
205.96 Total Impact Points

Institutions

  • 2012-2015
    • Heinrich-Heine-Universität Düsseldorf
      • Institute of Virology
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2011-2012
    • Johns Hopkins Bloomberg School of Public Health
      • Department of Biostatistics
      Baltimore, Maryland, United States
  • 2003-2012
    • Technische Universität Dortmund
      • Faculty of Statistics
      Dortmund, North Rhine-Westphalia, Germany
  • 2009-2011
    • Johns Hopkins University
      • • Department of Biostatistics
      • • Department of Medicine
      Baltimore, Maryland, United States