Biology subjects

Fischer, V.

Publications and source records attributed to Fischer, V..

7 recordsLinked to original sources

bioRxiv2026

Begonia manicata genome sequence reveals genetic basis underlying ornamental pigmentation

Plant genome sequences provide access to the gene repertoire of a species. This facilitates basic research, biotechnological processes, or horticultural applications. Here, we present the genome sequence of Begonia manicata and unravel the genes underlying the pigmentation of red structures emerging from its leaves and stems. Structural genes of the anthocyanin biosynthesis and corresponding regulatory genes were discovered to be upregulated in these red structures suggesting that the pigmentation is caused by the accumulation of anthocyanins. Our work provides a resource for future studies on pigmentation of Begoniaceae.

plant biology↗

bioRxiv2025

Using artificial intelligence-based software for an unbiased discrimination of immune cell subtypes in the fracture hematoma and bone marrow of non-osteoporotic and osteoporotic mice

It is well established that the early inflammatory response following fracture is essential for initiating subsequent bone regeneration. An imbalance in inflammation, whether within the innate or adaptive immune response, can result in impaired fracture healing. In our previous studies, we demonstrated that, for example, mice with ovariectomy-induced osteoporosis exhibit altered immune cell populations in the early fracture hematoma and bone marrow, leading to delayed healing. These analyses were conducted using conventional FACS/flow cytometry software, where surface marker expression was assessed using a single threshold based on isotype controls--a binary "yes or no" decision. Recent advances have highlighted that immune cell populations are often more heterogeneous, with distinct phenotypic subgroups depending on their polarization status. This has been particularly well documented for macrophage subpopulations (M1, M2, and intermediate polarization states). In light of this, we employed a commercially available artificial intelligence-based clustering software (Cytolution) to more accurately and objectively identify immune cell subpopulations. We re-analyzed flow cytometry raw data from fracture hematoma and bone marrow of non-osteoporotic and osteoporotic mice at day 1 after fracture. Our findings revealed distinct subclusters for granulocytes (27 subclusters), macrophages (7 subclusters), B cells (4 subclusters), and T cells (6 subclusters) within the fracture hematoma and bone marrow. Comparing osteoporotic and non-osteoporotic mice, we observed an increased abundance of a specific B cell subpopulation in osteoporotic mice, alongside a significant reduction of a particular granulocyte subpopulation in the early fracture hematoma. Several subclusters of granulocytes, T cells, and macrophages were also altered in the bone marrow. The specific role of these immune cell subclusters remains to be investigated in the future. These results suggest that AI-based clustering may provide a powerful tool for identifying immune cell phenotypes during bone regeneration, offering a more nuanced understanding of flow cytometry data.

immunology↗

bioRxiv2024

ClassiCOL: LC-MS/MS analysis for ancient species Classification via Collagen peptide ambiguation

LC-MS/MS extends on the MALDI-TOF ZooMS approach by providing fragmentation spectra for each peptide. However, ancient bone samples generate sparse datasets containing only a few collagen proteins, rendering target-decoy strategies unusable and increasing uncertainty in peptide annotation. ClassiCOL embraces and even extends this ambiguity using a novel isoBLAST approach. The exhaustive set of potential peptide candidates created in this way is then used to retain or reject different potential paths at each taxonomic branching point down to the taxonomic level attainable with the sample information, always allowing for potential mixtures in the process. As an end point, all considered ambiguity is graphically represented with a clear prioritization of the species in the sample. Using public as well as in-house data, we demonstrate the performance of this universal postprocessing approach on different instruments and explore the possibility of identifying genetic as well as sample mixtures. Diet reconstruction from 40,000 year old cave hyena coprolites illustrates the exciting potential of this approach. TeaserClassiCOL is a postprocessing tool that allows for more accurate species classification from LC-MS/MS measurements of collagen.

bioinformatics↗

bioRxiv2024

On the identification of differentially-active transcription factors from ATAC-seq data

ATAC-seq has emerged as a rich epigenome profiling technique, and is commonly used to identify Transcription Factors (TFs) underlying given phenomena. A number of methods can be used to identify differentially-active TFs through the accessibility of their DNA-binding motif, however little is known on the best approaches for doing so. Here we benchmark several such methods using a combination of curated datasets with various forms of short-term perturbations on known TFs, as well as semi-simulations. We include both methods specifically designed for this type of data as well as some that can be repurposed for it. We also investigate variations to these methods, and identify three particularly promising approaches (a chromVAR-limma workflow with critical adjustments, monaLisa and a combination of GC smooth quantile normalization and multivariate modeling). We further investigate the specific use of nucleosome-free fragments, the combination of top methods, and the impact of technical variation. Finally, we illustrate the use of the top methods on a novel dataset to characterize the impact on DNA accessibility of TRAnscription Factor TArgeting Chimeras (TRAFTAC), which can deplete TFs - in our case NFkB - at the protein level. Author summaryTranscription factors regulate gene expression by binding sites in the genome that often harbor a specific DNA motif. The collective accessibility of these motif-matching regions, measured by technologies such as ATAC-seq, can be used to infer the activity of the corresponding transcription factors. Here we use curated datasets of 11 TF-specific perturbations as well as 116 semi-simulated datasets to benchmark various methods for identifying factors that differ in activity between experimental conditions. We investigate important variations in the analysis and make recommendations pertaining to such analysis. Finally, we illustrate the application of the top methods to characterize the effects of a novel method for perturbing transcription factors at the protein level.

bioinformatics↗

bioRxiv2022

Global ecomorphological restructuring of dominant marine reptiles prior to the K/Pg mass extinction

Mosasaurid squamates were the dominant amniote predators in marine ecosystems during most of the Late Cretaceous. Evidence from multiple sites worldwide of a global mosasaurid community restructuring across the Campanian-Maastrichtian transition may have wide-ranging implications for the evolution of diversity of these top oceanic predators. In this study, we use a suite of biomechanical traits and functionally descriptive ratios to investigate how the morphofunctional disparity of mosasaurids evolved through time and space prior to the Cretaceous-Palaeogene (K/Pg) mass extinction. Our results suggest that the worldwide taxonomic turnover in mosasaurid community composition from Campanian to Maastrichtian is reflected by a notable increase in morphofunctional disparity on a global scale, but especially driven the North American record. Ecomorphospace occupation becomes more polarised during the late Maastrichtian, as the morphofunctional disparity of mosasaurids plateaus in the Southern Hemisphere and decreases in the Northern Hemisphere. We show that these changes are not associated with strong modifications in mosasaurid size, but rather with the functional capacities of their skulls, and that mosasaurid morphofunctional disparity was in decline in several provincial communities before the K-Pg mass extinction. Our study highlights region-specific patterns of disparity evolution, and the importance of assessing vertebrate extinctions both globally and regionally. Ecomorphological differentiation in mosasaurid communities, coupled with declines in other formerly abundant marine reptile groups, indicates widespread restructuring of higher trophic levels in marine food webs was well underway when the K-Pg mass extinction took place.

paleontology↗

bioRxiv2021

SUPT3H-less SAGA coactivator can assemble and function without significantly perturbing RNA polymerase II transcription in mammalian cells

Coactivator complexes regulate chromatin accessibility and transcription. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved coactivator complex. The core module scaffolds the entire SAGA complex and adopts a histone octamer-like structure, which consists of six histone fold domain (HFD)-containing proteins forming three histone fold (HF) pairs, to which the double HFD-containing SUPT3H adds an HF pair. Spt3, the yeast ortholog of SUPT3H, interacts genetically and biochemically with the TATA binding protein (TBP) and contributes to global RNA polymerase II (Pol II) transcription. Here we demonstrate that i) SAGA purified from human U2OS or mouse embryonic stem cells (mESC) can assemble without SUPT3H; ii) SUPT3H is not essential for mESC survival, iii) SUPT3H is required for mESC growth and self-renewal, and iv) the loss of SUPT3H from mammalian cells affects the transcription of only a specific subset of genes. Accordingly, in the absence of SUPT3H no major change in TBP accumulation at gene promoters was observed. Thus, SUPT3H is not required for the assembly of SAGA, TBP recruitment, or overall Pol II transcription, but plays a role in mESC growth and self-renewal. Our data further suggest that yeast and mammalian SAGA complexes contribute to transcription regulation by distinct mechanisms.

molecular biology↗

bioRxiv2021

Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA polymerase II transcription

Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, as Atxn7l3-/- embryos show developmental delay already at embryonic day (E) 7.5, while Usp22-/- embryos are normal at this stage, but die at E14.5. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, in contrast H2Bub1 levels were strongly increased in Atxn7l3 null embryos and derived cell lines. Our transcriptomic analyses carried out from wild type and Atxn7l3-/- mouse embryonic stem cells (mESCs), or primary mouse embryonic fibroblasts (MEFs) suggest that the ATXN7L3-related DUB activity regulates only a subset of genes in both cell types. However, the gene sets and the extent of their deregulation were different in mESCs and MEFs. Interestingly, the strong increase of H2Bub1 levels observed in the Atxn7l3-/- mESCs, or Atxn7l3-/- MEFs, does not correlate with the modest changes in RNA Polymerase II (Pol II) occupancy and lack of changes in Pol II elongation observed in the two Atxn7l3-/- cellular systems. These observations together indicate that deubiquitylation of histone H2Bub1 does not directly regulate global Pol II transcription elongation.

molecular biology↗