Papers by Fritz Sedlazeck
Genome biology, 2015
Mapping reads to a genome remains challenging, especially for non-model organisms with lower qual... more Mapping reads to a genome remains challenging, especially for non-model organisms with lower quality assemblies, or for organisms with higher mutation rates. While most research has focused on speeding up the mapping process, little attention has been paid to optimize the choice of mapper and parameters for a user's dataset. Here, we present Teaser, a software that assists in these choices through rapid automated benchmarking of different mappers and parameter settings for individualized data. Within minutes, Teaser completes a quantitative evaluation of an ensemble of mapping algorithms and parameters. We use Teaser to demonstrate how Bowtie2 can be optimized for different data.
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PLOS Pathogens, 2015
Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapt... more Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapting their transcriptional programs. Chromatin assembly factors are involved in the regulation of stress genes by modulating the histone density at these loci. Here, we report a novel role for the chromatin assembly-associated histone acetyltransferase complex NuB4 in regulating oxidative stress resistance, antifungal drug tolerance and virulence in C. albicans. Strikingly, depletion of the NuB4 catalytic subunit, the histone acetyltransferase Hat1, markedly increases resistance to oxidative stress and tolerance to azole antifungals. Hydrogen peroxide resistance in cells lacking Hat1 results from higher induction rates of oxidative stress gene expression, accompanied by reduced histone density as well as subsequent increased RNA polymerase recruitment. Furthermore, hat1Δ/Δ cells, despite showing growth defects in vitro, display reduced susceptibility to reactive oxygen-mediated killing by innate immune cells. Thus, clearance from infected mice is delayed although cells lacking Hat1 are severely compromised in killing the host. Interestingly, increased oxidative stress resistance and azole tolerance are phenocopied by the loss of histone chaperone complexes CAF-1 and HIR, respectively, suggesting a central role for NuB4 in the delivery of histones destined for chromatin assembly via distinct pathways. Remarkably, the oxidative stress phenotype of hat1Δ/Δ cells is a species-specific trait only found in C. albicans and members of the CTG clade. The reduced azole susceptibility appears to be conserved in a wider range of fungi. Thus, our work demonstrates how highly conserved chromatin assembly pathways can acquire new functions in pathogenic fungi during coevolution with the host.
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Bioinformatics
The advent of Next Generation Sequencing (NGS) technologies and the increase in read length and n... more The advent of Next Generation Sequencing (NGS) technologies and the increase in read length and number of reads per run poses a computational challenge to bioinformatics. The demand for sensible, inexpensive, and fast methods to align reads to a reference genome is constantly increasing. Due to the high sensitivity the Smith-Waterman (SW) algorithm is best suited for that. However, its high demand for computational resources makes it unpractical. Here we present an optimal SWimplementation for NGS data and demonstrate the advantages of using common and inexpensive high performance architectures to improve the computing time of NGS applications. We implemented a C++ library (MASon) that exploits graphic cards (CUDA, OpenCL) and CPU vector instructions (SSE, OpenCL) to efficiently handle millions of short local pairwise sequence alignments (36bp - 1,000bp). All libraries can be easily integrated into existing and upcoming NGS applications and allow programmers to optimally utilize mod...
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BMC Veterinary Research, 2015
Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma deve... more Cats infected with exogenous feline leukemia virus (exFeLV) have a higher chance of lymphoma development than uninfected cats. Furthermore, an increased exFeLV transcription has been detected in lymphomas compared to non-malignant tissues. The possible mechanisms of lymphoma development by exFeLV are insertional mutagenesis or persistent stimulation of host immune cells by viral antigens, bringing them at risk for malignant transformation. Vaccination of cats against exFeLV has in recent years decreased the overall infection rate in most countries. Nevertheless, an increasing number of lymphomas have been diagnosed among exFeLV-negative cats. Endogenous feline leukemia virus (enFeLV) is another retrovirus for which transcription has been observed in cat lymphomas. EnFeLV provirus elements are present in the germline of various cat species and share a high sequence similarity with exFeLV but, due to mutations, are incapable of producing infectious viral particles. However, recombination between exFeLV and enFeLV could produce infectious particles. We examined the FeLV expression in cats that have developed malignant lymphomas and discussed the possible mechanisms that could have induced malignant transformation. For expression analysis we used next-generation RNA-sequencing (RNA-Seq) and for validation reverse transcription quantitative PCR (RT-qPCR). First, we showed that there was no expression of exFeLV in all samples, which eliminates the possibility of recombination between exFeLV and enFeLV. Next, we analyzed the difference in expression of three enFeLV genes between control and lymphoma samples. Our analysis showed an average of 3.40-fold decreased viral expression for the three genes in lymphoma compared to control samples. The results were confirmed by RT-qPCR. There is a decreased expression of enFeLV genes in lymphomas versus control samples, which contradicts previous observations for the exFeLV. Our results suggest that a persistent stimulation of host immune cells is not an appropriate mechanism responsible for malignant transformation caused by feline endogenous retroviruses.
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Nucleic acids research, Jan 29, 2014
Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded ... more Adenosine deaminases that act on RNA (ADARs) deaminate adenosines to inosines in double-stranded RNAs including miRNA precursors. A to I editing is widespread and required for normal life. By comparing deep sequencing data of brain miRNAs from wild-type and ADAR2 deficient mouse strains, we detect editing sites and altered miRNA processing at high sensitivity. We detect 48 novel editing events in miRNAs. Some editing events reach frequencies of up to 80%. About half of all editing events depend on ADAR2 while some miRNAs are preferentially edited by ADAR1. Sixty-four percent of all editing events are located within the seed region of mature miRNAs. For the highly edited miR-3099, we experimentally prove retargeting of the edited miRNA to novel 3' UTRs. We show further that an abundant editing event in miR-497 promotes processing by Drosha of the corresponding pri-miRNA. We also detect reproducible changes in the abundance of specific miRNAs in ADAR2-deficient mice that occur ind...
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PLoS ONE, 2012
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Nature Biotechnology, 2013
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Genomics, 2013
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Genome Research, 2012
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Bioinformatics, 2013
When choosing a read mapper, one faces the trade off between speed and the ability to map reads i... more When choosing a read mapper, one faces the trade off between speed and the ability to map reads in highly polymorphic regions. Here, we report NextGenMap, a fast and accurate read mapper, which reduces this dilemma. NextGenMap aligns reads reliably to a reference genome even when the sequence difference between target and reference genome is large, i.e. highly polymorphic genome. At the same time, NextGenMap outperforms current mapping methods with respect to runtime and to the number of correctly mapped reads. NextGenMap efficiently uses the available hardware by exploiting multi-core CPUs as well as graphic cards (GPUs), if available. In addition, NextGenMap handles automatically any read data independent of read length and sequencing technology. NextGenMap source code and documentation are available at: http://cibiv.github.io/NextGenMap/. fritz.sedlazeck@univie.ac.at. Supplementary data are available at Bioinformatics online.
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Nature genetics, Jan 2, 2015
Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulac... more Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 and MD2 and a wild pineapple relative, Ananas bracteatus accession CB5. The pineapple genome has one fewer ancient whole-genome duplication event than sequenced grass genomes and a conserved karyotype with seven chromosomes from before the ρ duplication event. The pineapple lineage has transitioned from C3 photosynthesis to CAM, with CAM-related genes exhibiting a diel expression pattern in photosynthetic tissues. CAM pathway genes were enriched with cis-regulatory elements associated with the regulation of circadian clock genes, providing the first cis-regulatory link between CAM and circadian clock regulation. Pineapple CAM photosynthesis evolved by the reconfiguration of pathways in C3...
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Papers by Fritz Sedlazeck