Biology subjects

Andreotti, S.

Publications and source records attributed to Andreotti, S..

8 recordsLinked to original sources

bioRxiv2026

rhythmCI: an R package for rhythm detection using harmonic regression amplitude confidence intervals

Circadian clocks are evolutionarily conserved systems that orchestrate daily rhythms in human physiology, tissue behavior, and cellular function. In circadian research, the NanoString nCounter platform has emerged as a robust alternative to microarray and RNA sequencing. However, raw instrument output requires specialized preprocessing to handle technical noise. Furthermore, while harmonic regression is widely used to detect periodic signals in biological time-series data, evaluating rhythmicity remains highly challenging in clinical studies characterized by sparse sampling and small sample sizes. To address these limitations, we developed rhythmCI, an easy-to-use R package that integrates established normalization methods with a complete workflow for circadian data analysis. The package incorporates a bootstrapping procedure to estimate confidence intervals for harmonic regression amplitudes, offering a statistically transparent way to quantify rhythmicity in small-cohort studies. rhythmCI provides an end-to-end workflow for NanoString nCounter data, including automated preprocessing, normalization, and visualization. We evaluated the utility and accuracy of the package using synthetic time-series data generated with the Simphony framework, demonstrating that rhythmCI produces interpretable and reliable rhythmicity classifications under controlled simulation conditions. rhythmCI bridges a critical gap in circadian bioinformatics by offering a reliable method to characterize periodicity under challenging experimental designs typical of clinical research. By streamlining NanoString workflows and improving the statistical rigor of rhythm detection in small datasets, rhythmCI enhances the accessibility and reliability of circadian biology analysis.

bioinformatics↗

bioRxiv2025

Comparative metabolic profile of mice fed a grain-based controlled diet and a purified controlled diet

PurposeGrain-based control diets and purified diets are widely used in metabolic studies involving rodents, although their compositional differences may influence physiological outcomes and experimental interpretations. This study aimed to compare the metabolic profile of C57BL/6 mice fed a grain-based diet or a purified diet, both administered under normocaloric conditions. MethodsMale C57BL/6 mice (7 weeks old) were fed a grain-based diet or a purified diet for 12 weeks. Body mass and composition, fasting blood glucose, oral glucose tolerance, and plasma lipid profile (triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol) were evaluated. Statistical analyses were conducted using an unpaired Students t-test (P [≤] 0.05). ResultsNo significant differences were observed between groups in the evolution of body mass, body composition, fasting blood glucose, oral glucose tolerance, or plasma lipid parameters. ConclusionUnder normocaloric conditions, grain-based or purified control diets produce equivalent metabolic profiles in C57BL/6 mice, supporting their interchangeable use as control diets in metabolic research studies.

physiology↗

bioRxiv2025

Liraglutide exerts protective effects on MASLD independently of lipophagy, and the combination with kombucha presents no additional advantage

Metabolic dysfunction - associated steatotic liver disease (MASLD) has a high global prevalence, requiring effective therapeutic options. This study investigated the effects of liraglutide and kombucha, alone and in combination, in a murine model of high-fat diet (HFD)-induced MASLD. Metabolic parameters, body composition, liver histology, lipid profile, and markers of lipophagy were evaluated. The results demonstrate that liraglutide reduced body weight, fat mass, and lean mass, as well as food and caloric intake, fasting blood glucose, hepatic triglycerides (TG), steatosis, and fibrosis, improved the lipid profile and glucose tolerance, and increased lysosomal acid lipase (LAL) expression in the liver. Kombucha reduced lean mass, liver steatosis, hepatic TG, food and caloric intake, fasting blood glucose, low-density lipoprotein cholesterol (LDL-C), and liver fibrosis, in addition to improving glucose tolerance. However, the combination of treatments did not show synergistic effects superior to those of liraglutide alone. Although liraglutide independently impacted LAL expression, none of the other lipophagy markers were modulated in the liver, suggesting that the beneficial mechanisms of action are independent of the lipophagy pathway. It is concluded that both liraglutide and kombucha are valid strategies for mitigating MASLD, but the combination does not offer superior advantages over liraglutide monotherapy.

molecular biology↗

bioRxiv2025

Cytochrome c oxidase I deep amplicon sequencing for metabarcoding of equine strongyle communities: unexpectedly high Strongylus spp. burden in treated horses

Equines are parasitized by complex communities of Strongylidae (Nematoda) comprising multi-species infections. Currently, the Cyathostominae are most prevalent, while the Strongylus species are only rarely detected. Since eggs and, in most cases, infective larvae cannot be differentiated to species level, with the exception of Strongylus spp., species-specific knowledge of the pathology, epidemiology and ecology of these parasitic nematodes is limited. Reference sequence data for several cyathostomin species are limited or missing. Deep amplicon sequencing of internal transcribed spacer 2 (ITS-2) regions of nematodes has been used in equines previously, although barcoding studies demonstrate a better species resolution for the cytochrome c oxidase subunit I (COI) region. The present study introduces a nemabiome method based on the sequencing of COI fragments. This method was applied to compare third stage larvae, representing strongyle communities, derived from regularly treated (RT) and never treated (NT) equine populations from Brazil, France (only RT), Germany, Ukraine, the UK, and the USA. Samples were predominantly from horses, but some were obtained from Przewalskis horses (Ukraine), donkeys (Germany, Ukraine) and kulans (Ukraine). Most sequence reads (87.7%) were identified to the species level, but unclassified reads occurred more frequently in donkeys and kulans than horses. No obvious difference in species diversity and richness was observed between RT and NT equines. However, there were significant differences in species composition between the RT and NT groups. While Strongylus spp. were significantly more abundant in the NT groups, Cylicocyclus nassatus, Cylicostephanus longibursatus, and Cyathostomum catinatum were more abundant in the RT group, suggesting that strongyle communities in domestic equines may have been shaped by anthelmintic treatments in the last decades. The decreased classification success for reads from non-caballine equines suggests that there are more strongyle species specific for this rarely-investigated group and that additional efforts are needed to improve the sequence database, particularly for these hosts. Author summaryThis study shows that long-term deworming treatments have influenced strongyle nematode communities in equines. Our findings showed that regular deworming does not always reduce species richness and diversity. Noteworthy, we observed that the more pathogenic species such as Strongylus vulgaris and Strongylus edentatus were still present but in low abundance in equines. Due to their low abundance, less sensitive diagnostic methods, such as morphological examination of larval cultures might not detect these species, which would lead to an underestimated threat in equine herds. We applied an effective metabarcoding approach based on a reliable gene marker region to accurately detect these and other strongyle species in equines. The detection of various species was more effective for horse samples than for those from donkeys and kulans. An expansion of the current database that includes more specimens from more rare species obtained from different equine species can improve identification and understanding of these complex multi-species communities in the future. In summary, the study underscores the importance of continuing monitoring equine herds based on sensitive methods such as metabarcoding to evaluate the current nematode communities and to adapt and develop treatment strategies for managing strongyle infections in equines.

microbiology↗

bioRxiv2025

MegaPX: fast and space-efficient peptide assignment method using IBF-based multi-indexing

MotivationA central problem for metaproteomic analysis is the often-unknown taxonomic composition of the analyzed microbiomes. Using a database search, the standard approach requires prior knowledge of which proteins and taxa to include in the protein reference database or to use tailored metagenome-derived databases, which are expensive and error-prone in their generation. A possible strategy to circumvent this database search issue is de novo sequencing, where peptide sequences are directly identified from mass spectra. However, these sequences must still be mapped back to potentially extensive databases. Here, alignment-based approaches enable robust and precise results, with the potential drawback of high memory usage and long run times. ResultsWe present MegaPX, a software for rapidly classifying de novo peptide sequences against large protein databases. MegaPX implemented as a C++-based tool, uses an alignment-free, k-mer-based approach as a taxonomic classification method with the possibility of generating mutated reference databases for error-tolerant searching. It uses various algorithms, including interleaved Bloom filters, to efficiently compute approximate membership queries, ensuring fast processing times while querying and indexing large databases in a multi-indexing fashion. We demonstrate the potential of MegaPX by analyzing different samples, including metaproteomics, against extensive reference databases, highlighting its use as a fast screening tool. Availability and implementationMegaPXs source code and all related documentation files are freely available in a GitHub repository (https://github.com/rki-mf2/MegaPX) under the MIT License. ContactMuthT@rki.de Supplementary informationAll supplementary tables and figures are included at the end of the preprint.

bioinformatics↗

bioRxiv2021

Insights into standards of care: dexamethasone and antibodies against COVID-19 in hamster models

RationaleIn face of the ongoing SARS-CoV-2 pandemic, effective and well-understood treatment options are still scarce. While vaccines have proven instrumental in fighting SARS-CoV-2, their efficacy is challenged by vaccine hesitancy, novel variants and short-lasting immunity. Therefore, understanding and optimization of therapeutic options remains essential. ObjectivesWe aimed at generating a deeper understanding on how currently used drugs, specifically dexamethasone and anti-SARS-CoV-2 antibodies, affect SARS-CoV-2 infection and host responses. Possible synergistic effects of both substances are investigated to evaluate combinatorial treatments. MethodsBy using two COVID-19 hamster models, pulmonary immune responses were analyzed to characterize effects of treatment with either dexamethasone, anti-SARS-CoV-2 spike monoclonal antibody or a combination of both. scRNA sequencing was employed to reveal transcriptional response to treatment on a single cell level. Measurements and main resultsDexamethasone treatment resulted in similar or increased viral loads compared to controls. Anti-SARS-CoV-2 antibody treatment alone or combined with dexamethasone successfully reduced pulmonary viral burden. Dexamethasone exhibited strong anti-inflammatory effects and prevented fulminant disease in a severe COVID-19-like disease model. Combination therapy showed additive benefits with both anti-viral and anti-inflammatory potency. Bulk and single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon dexamethasone treatment and identified a candidate subpopulation of neutrophils specifically responsive to dexamethasone. ConclusionsOur analyses i) confirm the anti-inflammatory properties and indicate possible modes of action for dexamethasone, ii) validate anti-viral effects of anti-SARS-CoV-2 antibody treatment, and iii) reveal synergistic effects of a combination therapy and can thus inform more effective COVID-19 therapies.

molecular biology↗

bioRxiv2021

De Novo Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome, an Animal Model for Severe/Critical COVID-19

The Roborovski dwarf hamster Phodopus roborovskii belongs to the Phodopus genus, one of seven within Cricetinae subfamily. Like other rodents such as mice, rats or ferrets, hamsters can be important animal models for a range of diseases. Whereas the Syrian hamster from the genus Mesocricetus is now widely used as a model for mild to moderate COVID-19, Roborovski dwarf hamster show a severe to lethal course of disease upon infection with the novel human coronavirus SARS-CoV-2.

genomics↗

bioRxiv2020

Longitudinal omics in Syrian hamsters integrated with human data unravel complexity of moderate immune responses to SARS-CoV-2

In COVID-19, the immune response largely determines disease severity and is key to therapeutic strategies. Cellular mechanisms contributing to inflammatory lung injury and tissue repair in SARS-CoV-2 infection, particularly endothelial cell involvement, remain ill-defined. We performed detailed spatiotemporal analyses of cellular and molecular processes in SARS-CoV-2 infected Syrian hamsters. Comparison of hamster single-cell sequencing and proteomics with data sets from COVID-19 patients demonstrated inter-species concordance of cellular and molecular host-pathogen interactions. In depth vascular and pulmonary compartment analyses (i) supported the hypothesis that monocyte-derived macrophages dominate inflammation, (ii) revealed endothelial inflammation status and T-cell attraction, and (iii) showed that CD4+ and CD8+ cytotoxic T-cell responses precede viral elimination. Using the Syrian hamster model of self-limited moderate COVID-19, we defined the specific roles of endothelial and epithelial cells, among other myeloid and non-myeloid lung cell subtypes, for determining the disease course.

immunology↗