Biology subjects

Ebersberger, I.

Publications and source records attributed to Ebersberger, I..

3 recordsLinked to original sources

bioRxiv2018

Combined single cell profiling of expression and DNA methylation reveals splicing regulation and heterogeneity

BackgroundAlternative splicing is a key regulatory mechanism in eukaryotic cells and increases the effective number of functionally distinct gene products. Using bulk RNA sequencing, splicing variation has been studied across human tissues and in genetically diverse populations. This has identified disease-relevant splicing events, as well as associations between splicing and genomic variations, including sequence composition and conservation. However, variability in splicing between single cells from the same tissue or cell type and its determinants remain poorly understood.\n\nResultsWe applied parallel DNA methylation and transcriptome sequencing to differentiating human induced pluripotent stem cells to characterize splicing variation (exon skipping) and its determinants. Our results shows that variation in single-cell splicing can be accurately predicted based on local sequence composition and genomic features. We observe moderate but consistent contributions from local DNA methylation profiles to splicing variation across cells. A combined model that is built based on sequence as well as DNA methylation information accurately predicts different splicing modes of individual cassette exons (AUC=0.85). These categories include the conventional inclusion and exclusion patterns, but also more subtle modes of cell-to-cell variation in splicing. Finally, we identified and characterized associations between DNA methylation and splicing changes during cell differentiation.\n\nConclusionsOur study yields new insights into alternative splicing at the single-cell level and reveals a previously underappreciated link between DNA methylation variation and splicing.

bioinformatics↗

bioRxiv2018

The evolutionary traceability of proteins

Orthologs document the evolution of genes and metabolic capacities encoded in extant and ancient genomes. Orthologous genes that are detected across the full diversity of contemporary life allow reconstructing the gene set of LUCA, the last universal common ancestor. These genes presumably represent the functional repertoire common to - and necessary for - all living organisms. Design of artificial life has the potential to test this. Recently, a minimal gene (MG) set for a self-replicating cell was determined experimentally, and a surprisingly high number of genes have unknown functions and are not represented in LUCA. However, as similarity between orthologs decays with time, it becomes insufficient to infer common ancestry, leaving ancient gene set reconstructions incomplete and distorted to an unknown extent. Here we introduce the evolutionary traceability, together with the software protTrace, that quantifies, for each protein, the evolutionary distance beyond which the sensitivity of the ortholog search becomes limiting. We show that the LUCA set comprises only high-traceable proteins most of which have catalytic functions. We further show that proteins in the MG set lacking orthologs outside bacteria mostly have low traceability, leaving open whether their eukaryotic orthologs have just been overlooked. On the example of REC8, a protein essential for chromosome cohesion, we demonstrate how a traceability-informed adjustment of the search sensitivity identifies hitherto missed orthologs in the fast-evolving microsporidia. Taken together, the evolutionary traceability helps to differentiate between true absence and non-detection of orthologs, and thus improves our understanding about the evolutionary conservation of functional protein networks.

evolutionary biology↗

bioRxiv2016

An annotated draft genome for Radix auricularia(Gastropoda, Mollusca)

Molluscs are the second most species-rich phylum in the animal kingdom, yet only eleven genomes of this group have been published so far. Here, we present the draft genome sequence of the pulmonate freshwater snail Radix auricularia. Six whole genome shotgun libraries with different layouts were sequenced. The resulting assembly comprises 4,823 scaffolds with a cumulative length of 910 Mb and an overall read coverage of 72x. The assembly contains 94.6 % of a metazoan core gene collection, indicating an almost complete coverage of the coding fraction. The discrepancy of ~690 Mb compared to the estimated genome size of R. auricularia (1.6 Gb) results from a high repeat content of 70 % mainly comprising DNA transposons. The annotation of 17,338 protein coding genes was supported by the use of publicly-available transcriptome data. This draft will serve as starting point for further genomic and population genetic research in this scientifically important phylum.

genomics↗