Biology subjects

Beier, S.

Publications and source records attributed to Beier, S..

13 recordsLinked to original sources

bioRxiv2025

Spatiotemporal dynamics of tumor microenvironment remodelling

During tumorigenesis, interactions between tumor and stromal cells progressively remodel the tumor microenvironment (TME) towards pro-tumoral functions. Understanding early TME remodeling dynamics is therefore crucial for developing interceptive therapies. However, clinical samples typically provide isolated, late tumorigenesis snapshots. To overcome this limitation, we generated triple-negative breast cancer mice that develop multifocal, asynchronous tumors along a continuous luminal-to-basal transdifferentiation trajectory. Ordering spatial transcriptomes from 100+ ducts along this trajectory reveals the spatiotemporal dynamics of TME remodeling and underlying molecular mechanisms. Cancer-associated myofibroblasts (myCAFs) emerge as key players in advanced tumors, where they orchestrate pro-invasive remodeling of the tumor-stromal interface. myCAFs are conserved in patient-derived xenograft models and steer tumor trajectories towards invasive phenotypes when co-injected with tumor cells in syngeneic mice. Our study shows that temporal ordering of spatially-resolved disease snapshots unravels some of the molecular "forces" that, starting from the cell-of-origin, propel cells/microenvironments along a disease trajectory.

cancer biology↗

bioRxiv2025

Haplotype-resolved genome assembly of the tetraploid potato cultivar Desiree

Cultivar Desiree is an important model for potato functional genomics studies to assist breeding strategies. Here, we present a haplotype-resolved genome assembly of Desiree, achieved by assembling PacBio HiFi reads and Hi-C scaffolding, resulting in a high-contiguity chromosome-level assembly. We implemented a comprehensive annotation pipeline incorporating gene models and functional annotations from the Solanum tuberosum Phureja DM reference genome alongside RNA-seq reads to provide high-quality gene and transcript annotations. Additionally, we provide a genome-wide DNA methylation profile using Oxford Nanopore reads, enabling insights into potato epigenetics. The assembled genome, annotations, methylation and expression data are visualised in a publicly accessible genome browser (https://desiree.nib.si), providing a valuable resource for the potato research community.

plant biology↗

bioRxiv2023

DataPLAN: a web-based data management plan generator for the plant sciences

Research Data Management (RDM) is a system for the effective handling of research data that enables scientists to structure their research questions and ensure best practices throughout the data lifecycle, from acquisition, computation and annotation to data publication and re-use. Data management plans (DMPs) are documents that formally set out the RDM of a project and are required by many funding bodies. DMPs help to organize and structure RDM strategies, thus promoting data findability, accessibility, interoperability and reusability (FAIR). Although DMPs incorporate methods and standards that can be reused by different research projects, the standardization of DMP content is not as evident as the standardization of RDM practices and data/metadata. To address this issue in the plant sciences, we developed DataPLAN - a tool that combines a questionnaire with pre-written standardized responses. We wrapped the questionnaire in a serverless single-page web application that can then generate standardized responses from DMP templates. The current templates cater to plant research grant proposals for Horizon 2020, Horizon Europe and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). In the future the range of templates will be extended to accommodate other funding schemes, thereby enabling more users to generate their own templates. The DataPLAN web application is open-source and does not require an internet connection. By utilizing DataPLAN, the workload associated with creating, updating, and adhering to DMPs is significantly reduced.

plant biology↗

bioRxiv2022

The cost of adaptability: resource availability constrains functional stability under pulsed disturbances

Global change exposes ecosystems to changes in the frequency, magnitude and concomitancy of disturbances, which impact the composition and functioning. Here we experimentally evaluate effects of salinity disturbances and eutrophication on bacterial communities from coastal ecosystems. The resistance, resilience and functional stability of these communities is critically important for water quality, productivity and consequently ecosystem services, such as fishery yields. Yet, little is known about the underlying traits. Microbial functional stability can be maintained via resistance and resilience, which are reflected in genomic traits such as genome size and codon usage bias and may be linked to metabolic costs. To study the impact of pulsed disturbances on community assembly and functioning in dependence of metabolic costs, we performed a 41-days pulse disturbance experiment crossed with two levels of resource availability. Our setup triggered stochastic community re-assembly processes in all treatments. In contrast, we observed consistent and resource availability dependent patterns of superordinate community structural patterns and functioning, such as genomic trait distributions, species diversity, and functional resistance in response to disturbances. Genomic traits reflected the selection for taxa possessing resistant- and resilience-related traits, particularly under high nutrient availability. Our findings thereby mark an important step towards unraveling the compositional and genomic underpinnings of functional resistance in microbial communities after exposure to consecutive pulse disturbances. Our work demonstrates how resource availability alleviates metabolic constraints on resistance and resilience. This has important consequences for predicting water quality and ecosystem productivity of environments exposed to global change. SignificanceUnderstanding the responses of communities to disturbances is a prerequisite to predict ecosystem dynamics and thus highly relevant in light of global change. Microbial communities play key roles in numerous ecosystem functions and services, and the large diversity, rapid growth and phenotypic plasticity of microorganisms are thought to allow for high resistance and resilience. While potential metabolic costs associated with adaptions to fluctuating environments have been debated, little evidence supports trade-offs between resource availability and resistance and resilience. Here, we experimentally assessed the compositional and functional responses of an aquatic microbial model community to disturbances and systematically manipulated resource availability. Our results demonstrate that the capacity to tolerate environmental fluctuations is encoded in genomic traits and constrained by resource availability.

ecology↗

bioRxiv2022

DivBrowse - interactive visualization and exploratory data analysis of variant call matrices

BackgroundThe sequencing of whole genomes is becoming increasingly affordable. In this context large-scale sequencing projects are generating ever larger datasets of species-specific genomic diversity. As a consequence, more and more genomic data needs to be made easily accessible and analyzable to the scientific community. FindingsWe present DivBrowse, a web application for interactive visualization and exploratory analysis of genomic diversity data stored in Variant Call Format (VCF) files of any size. By seamlessly combining BLAST as an entry point together with interactive data analysis features such as principal component analysis in one graphical user interface, DivBrowse provides a novel and unique set of exploratory data analysis capabilities for genomic biodiversity datasets. The capability to integrate DivBrowse into existing web applications supports interoperability between different web applications. Built-in interactive computation of principal component analysis allows users to perform ad-hoc analysis of the population structure based on specific genetic elements such as genes and exons. Data interoperability is supported by the ability to export genomic diversity data in VCF and General Feature Format (GFF3) files. ConclusionDivBrowse offers a novel approach for interactive visualization and analysis of genomic diversity data and optionally also gene annotation data by including features like interactive calculation of variant frequencies and principal component analysis. The use of established standard file formats for data input supports interoperability and seamless deployment of application instances based on the data output of established bioinformatics pipelines.

bioinformatics↗

bioRxiv2022

Role of the two flagellar stators in swimming motility of Pseudomonas putida

In the soil bacterium Pseudomonas putida, the motor torque for flagellar rotation is generated by the two stators MotAB and MotCD. Here, we construct mutant strains, in which one or both stators are knocked out and investigate their swimming motility in fluids of different viscosity and in heterogeneous structured environments (semisolid agar). Besides bright-field imaging of single cell trajectories and spreading cultures, dual color fluorescence microscopy allows us to quantify the role of the stators in forming P. putidas three different swimming modes, where the flagellar bundle pushes, pulls, or wraps around the cell body. The MotAB stator is essential for swimming motility in liquids, while spreading in semisolid agar is not affected. Moreover, if the MotAB stator is knocked out, wrapped mode formation under low viscosity conditions is strongly impaired and only partly restored for increased viscosity and in semisolid agar. In contrast, when the MotCD stator is missing, cells are indistinguishable from the wild-type in fluid experiments, but spread much slower in semisolid agar. Analysis of the microscopic trajectories reveals that the MotCD knockout strain forms sessile clusters thereby reducing the number of motile cells, while the swimming speed is unaffected. Together, both stators ensure a robust wild-type that swims efficiently under different environmental conditions. IMPORTANCEBecause of its heterogeneous habitat, the soil bacterium Pseudomonas putida needs to swim efficiently under very different environmental conditions. In this paper, we knocked out the stators MotAB and MotCD to investigate their impact on swimming motility of P. putida. While the MotAB stator is crucial for swimming in fluids, in semisolid agar both stators are sufficient to sustain a fast swimming phenotype and increased frequencies of the wrapped mode, which is know to be beneficial for escaping mechanical traps. However, in contrast to the MotAB knock-out, a culture of MotCD knock-out cells spreads much slower in the agar as it forms non-motile clusters that reduce the amount of motile cells.

microbiology↗

bioRxiv2021

Trait-trait relationships and functional tradeoffs vary with genome size in prokaryotes

We report genomic traits that have been associated with the life history of prokaryotes and highlight conflicting findings concerning earlier observed trait correlations and tradeoffs. In order to address possible explanations for these contradictions we examined trait-trait variations of 11 genomic traits from ~ 18,000 sequenced genomes. The studied trait-trait variations suggested: (i) the predominance of two resistance and resilience-related orthogonal axes and (ii) at least in free living species with large effective population sizes whose evolution is little affected by genetic drift an overlap between a resilience axis and an axis of resource usage efficiency. These findings imply that resistance associated traits of prokaryotes are globally decoupled from resilience related traits and in the case of free-living communities also from resource use efficiencies associated traits. However, further inspection of pairwise scatterplots showed that resistance and resilience traits tended to be positively related for genomes up to roughly five million base pairs and negatively for larger genomes. This in turn may preclude a globally consistent assignment of prokaryote genomic traits to the competitor - stress-tolerator - ruderal (CSR) schema that sorts species depending on their location along disturbance and productivity gradients into three ecological strategies and may serve as an explanation for conflicting findings from earlier studies. All reviewed genomic traits featured significant phylogenetic signals and we propose that our trait table can be applied to extrapolate genomic traits from taxonomic marker genes. This will enable to empirically evaluate the assembly of these genomic traits in prokaryotic communities from different habitats and under different productivity and disturbance scenarios as predicted via the resistance-resilience framework formulated here.

ecology↗

bioRxiv2021

Integration of chemosensing and carbon catabolite repression impacts fungal enzyme regulation and plant associations

Fungal metabolism and enzyme production are regulated by nutrient availability and by interactions with the living environment. We investigated the mechanisms underpinning adaptation of the biotechnological fungus Trichoderma reesei to decaying plant biomass versus living plants. We found that concentration-gated response to glucose, the main molecule sensed from dead plant biomass, is mediated by a conserved signaling pathway downstream of G protein-coupled receptors (GPCRs), while the carbon catabolite repressor CRE1 is critical for glucose concentration gating. The GPCRs CSG1 and CSG2 are further required for root colonization and formation of appressorium like structures on plant surfaces. Acceleration of sexual development in the presence of plant roots and their interactions with fruiting bodies indicates preferential association with plants. Our results reveal a complex sensing network governing resource distribution, enzyme production and fungal development that explains previously observed phenomena in fermentations and opens new perspectives for industrial strain improvement and agriculture.

microbiology↗

bioRxiv2021

Panakeia - A universal tool for bacterial pangenome analysis

AO_SCPLOWBSTRACTC_SCPLOWWe present Panakeia, a tool which strives to be easy to use and providing a detailed view of the pangenome structure which can efficiently be utilised for discovery, or further in-depth analysis, of features of interest. It analyses synteny and multiple structural patterns of the pangenome, giving insights into the biological diversity and evolution of the studied taxon. Panakeia hence provides both broad and detailed information on the structure of a pangenome, for diverse and highly clonal populations of bacteria. Development of new pan-genome analysis tools is important, as the pangenome of a microbial species has become an important method to define the diversity of a selected taxon, most commonly a species, in the last years. This enables comparison of strains from different ecological niches and can be used to define the functional potential in a bacterial population. It gives us a much better view of microbial genomics than can be gained from singular genomes which after all are just single representatives of a much more varied population. Previously published pangenome tools often reduce the information to a presence/absence matrix of unconnected genes or generate massive hard to interpret output graphs. However, Panakeia includes synteny and structural information and presents it in a way that can readily be used for further analysis. Panakeia can be downloaded at https://github.com/BioSina/Panakeia.

bioinformatics↗

bioRxiv2020

Model-based prediction of bacterial population dynamics in gastrointestinal infection

The complex interplay of a pathogen with the host immune response and the endogenous microbiome determines the course and outcome of gastrointestinal infection (GI). Expansion of a pathogen within the gastrointestinal tract implies an increased risk to develop systemic infection. Through computational modeling, we aimed to calculate bacterial population dynamics in GI in order to predict infection course and outcome. For the implementation and parameterization of the model, oral mouse infection experiments with Yersinia enterocolitica were used. Our model takes into account pathogen specific characteristics, such as virulence, as well as host properties, such as microbial colonization resistance or immune responses. We were able to confirm the model calculations in these scenarios by experimental mouse infections and show that it is possible to computationally predict the infection course. Far future clinical application of computational modeling of infections may pave the way for personalized treatment and prevention strategies of GI.

microbiology↗

bioRxiv2019

Lack of regularity between letters impacts word recognition performance

Physical inter-letter dissimilarity has been suggested as a solution to increase perceptual differences between letter shapes and hence a solution to improve reading performance. However, the deleterious effects of font tuning suggest that low inter-letter regularity (due to the enhancement of specific letter features to make them more differentiable) may impair word recognition performance. The aim of the present investigation was 1) to validate our hypothesis that reducing inter-letter regularity impairs reading performance, as suggested by font tuning, and 2) to test whether some forms of non-regularities could impair visual word recognition more. To do so, we designed four new fonts. For each font we induced one type of increased perceptual difference: for the first font, the letters have longer extender length; for the second font, the letters have different slants; and for the third font, the letters have different font cases. We also designed a fourth font where letters differ on all three aspects (worst regularity across letters). Word recognition performance was measured for each of the four fonts in comparison to a traditional sans serif font (best regularity across letters) through a lexical decision task. Results showed a significant decrease in word recognition performance only for the fonts with mixed-case letters, suggesting that fonts with low regularity, such as mixed-case letters, should be avoided in the definition of new \"optimal\" fonts. Letter recognition performance measured for the five different fonts through a trigram recognition task showed that this effect is not consistently due to poor letter identification.

scientific communication and education↗

bioRxiv2019

Leaf Variegation and Impaired Chloroplast Development Caused by a Truncated CCT Domain gene in albostrians Barley

Chloroplasts fuel plant development and growth by converting solar into chemical energy. They mature from proplastids through the concerted action of genes in both the organellar and the nuclear genome. Defects in such genes impair chloroplast development and may lead to pigment-deficient seedlings or seedlings with variegated leaves. Such mutants are instrumental as tools for dissecting genetic factors underlying the mechanisms involved in chloroplast biogenesis. Characterization of the green-white variegated albostrians mutant of barley has greatly broadened the field of chloroplast biology including the discovery of retrograde signaling. Here, we report the identification of the ALBOSTRIANS gene HvAST by positional cloning as well as its functional validation based on independently induced mutants by TILLING and RNA-guided Cas9 endonuclease mediated gene editing. The phenotypes of the independent HvAST mutants imply residual activity of HvAST in the original albostrians allele conferring an imperfect penetrance of the variegated phenotype even at homozygous state of the mutation. HvAST is a homolog of the Arabidopsis thaliana CCT Motif transcription factor gene AtCIA2, which was reported to be involved in the expression of nuclear genes essential for chloroplast biogenesis. Interestingly, in barley we localized HvAST to the chloroplast indicating novel without any clear evidence of nuclear localization. One-sentence summaryLeaf variegation in the barley mutant albostrians is caused by mutation of a single CCT-domain containing gene with residual activity, which is directed to the chloroplast.

genetics↗

bioRxiv2019

Annotated bacterial chromosomes from frame-shift-corrected long read metagenomic data

BackgroundShort-read sequencing technologies have long been the work-horse of microbiome analysis. Continuing technological advances are making the application of long-read sequencing to metagenomic samples increasingly feasible.\n\nResultsWe demonstrate that whole bacterial chromosomes can be obtained from a complex community, by application of MinION sequencing to a sample from an EBPR bio-reactor, producing 6Gb of sequence that assembles in to multiple closed bacterial chromosomes. We provide a simple pipeline for processing such data, which includes a new approach to correcting erroneous frame-shifts.\n\nConclusionsAdvances in long read sequencing technology and corresponding algorithms will allow the routine extraction of whole chromosomes from environmental samples, providing a more detailed picture of individual members of a microbiome.

bioinformatics↗