Arndt von Haeseler

Arndt von Haeseler
University of Vienna | UniWien

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379
Publications
58,362
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46,347
Citations

Publications

Publications (379)
Article
Full-text available
Organoids enable in vitro modeling of complex developmental processes and disease pathologies. Like most 3D cultures, organoids lack sufficient oxygen supply and therefore experience cellular stress. These negative effects are particularly prominent in complex models, such as brain organoids, and can affect lineage commitment. Here, we analyze brai...
Preprint
We develop a Fokker-Planck theory of tissue growth with three types of cells (symmetrically dividing, asymmetrically dividing and non-dividing) as main agents to study the growth dynamics of human cerebral organoids. Fitting the theory to lineage tracing data obtained in next generation sequencing experiments, we show that the growth of cerebral or...
Preprint
Full-text available
Organoids enable disease modeling in complex and structured human tissue, in vitro. Like most 3D models, they lack sufficient oxygen supply, leading to cellular stress. These negative effects are particularly prominent in complex models, like brain organoids, where they can prevent proper lineage commitment. Here, we analyze brain organoid and feta...
Article
Full-text available
Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expres...
Preprint
Full-text available
Selecting the best model of sequence evolution for a multiple sequence alignment (MSA) constitutes the first step of phylogenetic tree reconstruction. Common approaches for inferring nucleotide models typically apply maximum likelihood (ML) methods, with discrimination between models determined by one of several information criteria. This requires...
Preprint
Full-text available
Cerebral organoids model the development of the human brain and have become an indispensable tool for studying neural development and neuro-developmental diseases. Comprehensive whole-organoid lineage tracing has revealed the fates of the lineages arising from each initial stem cells to be highly diverse, with lineage sizes ranging from one to more...
Article
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Ribosomal RNA genes (rDNAs) are located in large domains of hundreds of rDNA units organized in a head-to-tail manner. The proper and stable inheritance of rDNA clusters is of paramount importance for survival. Yet, these highly repetitive elements pose a potential risk to the genome since they can undergo non-allelic exchanges. Here, we review the...
Article
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The increasing incidence of antimicrobial resistance (AMR) is a major global challenge. Routine techniques for molecular AMR marker detection are largely based on low-plex PCR and detect dozens to hundreds of AMR markers. To allow for comprehensive and sensitive profiling of AMR markers, we developed a capture-based next generation sequencing (NGS)...
Preprint
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Recent population studies are ever growing in size of samples to investigate the diversity of a given population or species. These studies reveal ever new polymorphism that lead to important insights into the mechanisms of evolution, but are also important for the interpretation of these variations. Nevertheless, while the full catalog of variation...
Article
Full-text available
Meiosis is a specialized cell division that gives rise to genetically distinct gametic cells. Meiosis relies on the tightly controlled formation of DNA double-strand breaks (DSBs) and their repair via homologous recombination for correct chromosome segregation. Like all forms of DNA damage, meiotic DSBs are potentially harmful and their formation a...
Article
Full-text available
Despite vast differences between organisms, some characteristics of their genomes are conserved, such as the nucleolus organizing region (NOR). The NOR is constituted of multiple , highly repetitive rDNA genes, encoding the catalytic ribosomal core RNAs which are transcribed from 45S rDNA units. Their precise sequence information and organization r...
Article
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Vertebrate behavior is strongly influenced by light. Light receptors, encoded by functional opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despite their conserved widespread occurrence, the nonvis...
Article
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Genetic divergence of populations in the presence of gene flow is a central theme in speciation research. Theory predicts that divergence can happen with full range overlap – in sympatry – driven by ecological factors, but there are few empirical examples of how ecologically divergent selection can overcome gene flow and lead to reproductive isolat...
Article
Loss-of-function (LOF) screens provide a powerful approach to identify regulators in biological processes. Pioneered in laboratory animals, LOF screens of human genes are currently restricted to two-dimensional cell cultures, which hinders the testing of gene functions requiring tissue context. Here, we present CRISPR–lineage tracing at cellular re...
Article
Full-text available
Models of sequence evolution typically assume that all sequences are possible. However, restriction enzymes that cut DNA at specific recognition sites provide an example where carrying a recognition site can be lethal. Motivated by this observation, we studied the set of strings over a finite alphabet with taboos, that is, with prohibited substring...
Article
Full-text available
Poly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks...
Article
Full-text available
Light-dependent and dark-operative protochlorophyllide oxidoreductases (LPORs and DPORs) are evolutionary and structurally distinct enzymes that are essential for the synthesis of (bacterio)chlorophyll, the primary pigment needed for both anoxygenic and oxygenic photosynthesis. In contrast to the long-held hypothesis that LPORs are only present in...
Article
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SolariX is a compendium of DNA sequence tags from the nucleotide binding site (NBS) domain of disease resistance genes of the common potato, Solanum tuberosum Group Tuberosum. The sequences, which we call NBS tags, for nearly all NBS domains from 91 genomes—representing a wide range of historical and contemporary potato cultivars, 24 breeding progr...
Article
Full-text available
Maximum likelihood and maximum parsimony are two key methods for phylogenetic tree reconstruction. Under certain conditions, each of these two methods can perform more or less efficiently, resulting in unresolved or disputed phylogenies. We show that a neural network can distinguish between four-taxon alignments that were evolved under conditions s...
Preprint
Full-text available
Cell fate transitions depend on balanced rewiring of transcription and translation programmes to mediate ordered developmental progression. Here we identify a feedback loop between nonsense-mediated mRNA decay (NMD) and translation initiation. We show that NMD controls the translation initiation factor Eif4a2 and its premature termination codon enc...
Preprint
Full-text available
Poly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks...
Article
Full-text available
In animals, the most common type of RNA editing is the deamination of adenosines (A) into inosines (I). Because inosines base-pair with cytosines (C), they are interpreted as guanosines (G) by the cellular machinery and genomically encoded G alleles at edited sites mimic the function of edited RNAs. The contribution of this hardwiring effect on gen...
Article
Full-text available
IQ-TREE (http://www.iqtree.org, last accessed February 6, 2020) is a user-friendly and widely used software package for phylogenetic inference using maximum likelihood. Since the release of version 1 in 2014, we have continuously expanded IQ-TREE to integrate a plethora of new models of sequence evolution and efficient computational approaches of p...
Preprint
Full-text available
IQ-TREE (http://www.iqtree.org) is a user-friendly and widely used software package for phylogenetic inference using maximum likelihood. Since the release of version 1 in 2014, we have continuously expanded IQ-TREE to integrate a plethora of new models of sequence evolution and efficient computational approaches of phylogenetic inference to deal wi...
Preprint
Full-text available
Maximum likelihood and maximum parsimony are two key methods for phylogenetic tree reconstruction. Under certain conditions, each of these two methods can perform more or less efficiently than the other. We show that a neural network can efficiently distinguish between four-taxon alignments that were evolved under conditions conducive to long-branc...
Article
Full-text available
Insertional mutant libraries of microorganisms can be applied in negative depletion screens to decipher gene functions. Because of underrepresentation in colonized tissue, one major bottleneck is analysis of species that colonize hosts. To overcome this, we developed insertion pool sequencing (iPool‐Seq). iPool‐Seq allows direct analysis of coloniz...
Article
Molecular sequence data that have evolved under the influence of heterotachous evolutionary processes are known to mislead phylogenetic inference. We introduce the General Heterogeneous evolution On a Single Topology (GHOST) model of sequence evolution, implemented under a maximum-likelihood framework in the phylogenetic program IQ-TREE (http://www...
Preprint
Full-text available
Vertebrate behavior is strongly influenced by light. Photoreceptors, encoded by Opsins, are present inside the vertebrate brain and peripheral tissues. Their non-visual functions are largely enigmatic. We focus on tmt-opsin1b and 2 , c-Opsins with ancestral-type sequence features, conserved across several vertebrate phyla and with partly similar ex...
Article
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Background Methods to read out naturally occurring or experimentally introduced nucleic acid modifications are emerging as powerful tools to study dynamic cellular processes. The recovery, quantification and interpretation of such events in high-throughput sequencing datasets demands specialized bioinformatics approaches. Results Here, we present...
Article
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Molecular phylogenetics has neglected polymorphisms within present and ancestral populations for a long time. Recently, multispecies coalescent based methods have increased in popularity, however, their application is limited to a small number of species and individuals. We introduced a polymorphism-aware phylogenetic model (PoMo), which overcomes...
Article
Full-text available
Many marine animals, ranging from corals to fishes, synchronise reproduction to lunar cycles. In the annelid Platynereis dumerilii, this timing is orchestrated by an endogenous monthly (circalunar) clock entrained by moonlight. Whereas daily (circadian) clocks cause extensive transcriptomic and proteomic changes, the quality and quantity of regulat...
Article
Full-text available
Fast and affordable benchtop sequencers are becoming more important in improving personalized medical treatment. Still, distinguishing genetic variants between healthy and diseased individuals from sequencing errors remains a challenge. Here we present VARIFI, a pipeline for finding reliable genetic variants (single nucleotide polymorphisms (SNPs)...
Article
Full-text available
Orthologs document the evolution of genes and metabolic capacities encoded in extant and ancient genomes. However, the similarity between orthologs decays with time, and ultimately it becomes insufficient to infer common ancestry. This leaves ancient gene set reconstructions incomplete and distorted to an unknown extent. Here we introduce the "evol...
Preprint
Full-text available
Molecular phylogenetics has neglected polymorphisms within present and ancestral populations for a long time. Recently, multispecies coalescent based methods have increased in popularity, however, their application is limited to a small number of species and individuals. We introduced a polymorphism-aware phylogenetic model (PoMo), which overcomes...
Article
Full-text available
Structural variations are the greatest source of genetic variation, but they remain poorly understood because of technological limitations. Single-molecule long-read sequencing has the potential to dramatically advance the field, although high error rates are a challenge with existing methods. Addressing this need, we introduce open-source methods...
Article
Full-text available
Author summary Insertion mutant screens are widely used to identify genotype–phenotype relationships. In negative selection screens, a major limitation is the efficient identification of mutants that are lost or retained after selection. To identify these mutants, the two genomic sequences flanking the insertion cassette must be found. However, pin...
Data
Workflow of pooled infection of maize. For each replicate of the U. maydis mutant collection, at least 100 maize plants of the accession EGB were potted. Mutants were grown on selective plates for 2–3 days. From plates, precultures were inoculated and grown ON. The precultures were used for inoculation of the main cultures to avoid dead material in...
Data
Tn5 fragmentation of gDNA with modified adapters. Recombinantly produced hyperactive Tn5 was tested with standard Tn5-ME-A and custom UMI-ME-A on 1 μg gDNA of U. maydis-infected maize tissue with indicated concentrations. gDNA; genomic DNA; In, Input; M, Marker 1 kb-ladder (Thermo Scientific); ME, mosaic end; Tn5-ME-A, Tn5-ME-Adapter; UMI-ME-A, UMI...
Data
Sensitivity of iPool-Seq. Estimated sensitivity of iPool-Seq for a genome-wide library of U. maydis mutants. Model shows for different (1 up to 100) mutant copies detected in the input sample for the sensitivity of virulence factor detection. Depicted model curves are given assuming 3% of all mutants have a reduced virulence of log2(FC) −1.53 and l...
Data
iPool-Seq analysis pipeline description. iPool-Seq, insertion Pool-Sequencing. (PDF)
Data
Key primers used in this study. (XLSX)
Data
U. maydis mutants used for the internal reference set. (XLSX)
Data
iPool-Seq analysis pipeline. iPool-Seq, insertion Pool-Sequencing. (TGZ)
Data
U. maydis genes targeted for insertional mutagenesis. (XLSX)
Data
Significantly depleted U. maydis mutants identified by iPool-Seq. iPool-Seq, insertion Pool-Sequencing. (XLSX)
Data
q-Values of U. maydis mutant strains. (XLSX)
Data
Symptom rating of mutant strains. (XLSX)
Article
Full-text available
Ammonia-oxidising archaea (AOA) are ubiquitous and abundant in nature and play a major role in nitrogen cycling. AOA have been studied intensively based on the amoA gene (encoding ammonia monooxygenase subunit A), making it the most sequenced functional marker gene. Here, based on extensive phylogenetic and meta-data analyses of 33,378 curated arch...