Biology subjects

Ebeling, M.

Publications and source records attributed to Ebeling, M..

4 recordsLinked to original sources

bioRxiv2023

splicekit: a comprehensive toolkit for splicing analysis from short-read RNA-seq

MotivationAnalysis of alternative splicing using short-read RNA-seq data is a complex process that involves several steps: alignment of reads to the reference genome, identification of alternatively spliced features, motif discovery, analysis of RNA-protein binding near donor and acceptor splice sites, and exploratory data visualization. ResultsWe introduce splicekit, a python package that provides a comprehensive set of tools for conducting splicing analysis. Availability and implementationhttps://github.com/bedapub/splicekit and over PyPI.

bioinformatics↗

bioRxiv2022

Selective oxytocin receptor activation prevents prefrontal circuit dysfunction and social behavioral alterations in response to chronic prefrontal cortex activation in rats

Social behavioral changes are a hallmark of several neurodevelopmental and neuropsychiatric conditions, nevertheless the underlying neural substrates of such dysfunction remain poorly understood. Building evidence points to the prefrontal cortex (PFC) as one of the key brain regions that orchestrates social behavior. We used this concept with the aim to develop a translational rat model of social-circuit dysfunction, the chronic PFC activation model (CPA). Chemogenetic designer receptor hM3Dq was used to induce chronic activation of the PFC over 10 days, and the behavioral and electrophysiological signatures of prolonged PFC hyperactivity were evaluated. To test the sensitivity of this model to pharmacological interventions on longer timescales, and validate its translational potential, the rats were treated with our novel highly selective oxytocin receptor (OXTR) agonist RO6958375, which has a significantly improved pharmacokinetic profile over oxytocin. CPA rats showed reduced sociability in the three-chamber sociability test, and a concomitant decrease in neuronal excitability and synaptic transmission within the PFC as measured by electrophysiological recordings in acute slice preparation. Sub-chronic treatment with a low dose of the novel OXTR agonist following CPA interferes with the emergence of PFC circuit dysfunction, abnormal social behavior and specific transcriptomic changes. These results demonstrate that sustained PFC hyperactivity modifies circuit characteristics and social behaviors in ways that can be modulated by selective OXTR activation and that this model may be used to understand the circuit recruitment of prosocial therapies in drug discovery.

neuroscience↗

bioRxiv2020

Besca, a single-cell transcriptomics analysis toolkit to accelerate translational research

Single-cell RNA sequencing (scRNA-seq) revolutionised our understanding of disease biology and presented the promise of transforming translational research. We developed Besca, a toolkit that streamlines scRNA-seq analyses according to current best practices. A standard workflow covers quality control, filtering, and clustering. Two complementary Besca modules, utilizing hierarchical cell signatures or supervised machine learning, automate cell annotation and provide harmonised nomenclatures across studies. Subsequently, Besca enables estimation of cell type proportions in bulk transcriptomics studies. Using multiple heterogeneous scRNA-seq datasets we show how Besca aids acceleration, interoperability, reusability, and interpretability of scRNA-seq data analysis, crucial aspects in translational research and beyond.

bioinformatics↗

bioRxiv2017

Draft genome of the Heterotardigrade Milnesium tardigradum sheds light on ecdysozoan evolution

Tardigrades are among the most stress tolerant animals and survived even unassisted exposure to space in low earth orbit. Still, the adaptations leading to these unusual physiological features remain unclear. Even the phylogenetic position of this phylum within the Ecdysozoa is unclear. Complete genome sequences might help to address these questions as genomic adaptations can be revealed and phylogenetic reconstructions can be based on new markers. Here, we present a first draft genome of a species from the family Milnesiidae, namely Milnesium tardigradum. We consistently place M. tardigradum and the two previously sequenced Hypsibiidae species, Hypsibius dujardini and Ramazzottius varieornatus, as sister group of the nematodes with the arthropods as outgroup. Based on this placement, we identify a massive gene loss thus far attributed to the nematodes which predates their split from the tardigrades. We provide a comprehensive catalog of protein domain expansions linked to stress response and show that previously identified tardigrade-unique proteins are erratically distributed across the genome of M. tardigradum. We further suggest alternative pathways to cope with high stress levels that are yet unexplored in tardigrades and further promote the phylum Tardigrada as a rich source of stress protection genes and mechanisms.

evolutionary biology↗