0000000000825599
AUTHOR
Hristo Todorov
showing 11 related works from this author
Reliability of genomic variants across different next-generation sequencing platforms and bioinformatic processing pipelines
2021
Abstract Background Next Generation Sequencing (NGS) is the fundament of various studies, providing insights into questions from biology and medicine. Nevertheless, integrating data from different experimental backgrounds can introduce strong biases. In order to methodically investigate the magnitude of systematic errors in single nucleotide variant calls, we performed a cross-sectional observational study on a genomic cohort of 99 subjects each sequenced via (i) Illumina HiSeq X, (ii) Illumina HiSeq, and (iii) Complete Genomics and processed with the respective bioinformatic pipeline. We also repeated variant calling for the Illumina cohorts with GATK, which allowed us to investigate the e…
Long‐term molecular differences between resilient and susceptible mice after a single traumatic exposure
2022
Post-traumatic stress disorder (PTSD) is a heterogeneous disorder induced by trauma, resulting in severe long-term impairments of an individual's mental health. PTSD does not develop in every individual and, thus, some individuals are more resilient. However, the underlying molecular mechanisms are poorly understood. Here, we aimed to elucidate these processes.We used a single-trauma PTSD model in mice to induce long-term maladaptive behaviours and profiled the mice 4 weeks after trauma into resilient or susceptible individuals. The classification of phenotype was based on individual responses in different behavioural experiments. We analysed microbiome, circulating endocannabinoids, and lo…
The gut microbiota instructs the hepatic endothelial cell transcriptome
2021
Summary The gut microbiota affects remote organ functions but its impact on organotypic endothelial cell (EC) transcriptomes remains unexplored. The liver endothelium encounters microbiota-derived signals and metabolites via the portal circulation. To pinpoint how gut commensals affect the hepatic sinusoidal endothelium, a magnetic cell sorting protocol, combined with fluorescence-activated cell sorting, was used to isolate hepatic sinusoidal ECs from germ-free (GF) and conventionally raised (CONV-R) mice for transcriptome analysis by RNA sequencing. This resulted in a comprehensive map of microbiota-regulated hepatic EC-specific transcriptome profiles. Gene Ontology analysis revealed that …
Principal components analysis: theory and application to gene expression data analysis
2018
Advances in computational power have enabled research to generate significant amounts of data related to complex biological problems. Consequently, applying appropriate data analysis techniques has become paramount to tackle this complexity. However, theoretical understanding of statistical methods is necessary to ensure that the correct method is used and that sound inferences are made based on the analysis. In this article, we elaborate on the theory behind principal components analysis (PCA), which has become a favoured multivariate statistical tool in the field of omics-data analysis. We discuss the necessary prerequisites and steps to produce statistically valid results and provide gui…
N6 -Methyladenosine Modification in Chronic Stress Response Due to Social Hierarchy Positioning of Mice
2021
Appropriately responding to stressful events is essential for maintaining health and well-being of any organism. Concerning social stress, the response is not always as straightforward as reacting to physical stressors, e.g., extreme heat, and thus has to be balanced subtly. Particularly, regulatory mechanisms contributing to gaining resilience in the face of mild social stress are not fully deciphered yet. We employed an intrinsic social hierarchy stress paradigm in mice of both sexes to identify critical factors for potential coping strategies. While global transcriptomic changes could not be observed in male mice, several genes previously reported to be involved in synaptic plasticity, l…
The Microbiota Promotes Arterial Thrombosis in Low-Density Lipoprotein Receptor-Deficient Mice
2019
Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF Ldlr−/− mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished ex vivo thrombus formation under arterial flow conditions.
Applying univariate vs. multivariate statistics to investigate therapeutic efficacy in (pre)clinical trials: A Monte Carlo simulation study on the ex…
2020
BackgroundSmall sample sizes combined with multiple correlated endpoints pose a major challenge in the statistical analysis of preclinical neurotrauma studies. The standard approach of applying univariate tests on individual response variables has the advantage of simplicity of interpretation, but it fails to account for the covariance/correlation in the data. In contrast, multivariate statistical techniques might more adequately capture the multi-dimensional pathophysiological pattern of neurotrauma and therefore provide increased sensitivity to detect treatment effects.ResultsWe systematically evaluated the performance of univariate ANOVA, Welch's ANOVA and linear mixed effects models ver…
Dynamic longitudinal behavior in animals exposed to chronic social defeat stress
2020
AbstractChronic social defeat (CSD) can lead to impairments in social interaction and other behaviors that are supposed to model features of major depressive disorder (MDD). Not all animals subjected to CSD, however, develop these impairments, and maintained social interaction in some animals is widely used as a model for resilience to stress-induced mental dysfunctions. So far, animals have mainly been studied shortly (24 hours and 7 days) after CSD exposure and longitudinal development of behavioral phenotypes in individual animals has been mostly neglected. We have analyzed social interaction and novel object recognition behavior of stressed mice at different time points after CSD and ha…
Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient…
2020
The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr(-/-)) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemicLdlr(-/-)mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GFLdlr(-/-)mice …
Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse
2020
Alzheimer’s disease (AD) is the most common form of dementia. Besides its cognitive phenotype, AD leads to crucial changes in gut microbiome composition in model mice and in patients, but the reported data are still highly inconsistent. Therefore, we investigated chronic effects of AD-characteristic neurotoxic amyloid-β (Aβ) peptides as provided by transgenic overexpression (5xFAD mouse model) and acute effects due to oral application of Aβ on gut microbes. Astonishingly, one-time feeding of wild type mice with Aβ42 provoked immediate changes in gut microbiome composition (β diversity) as compared to controls. Such obvious changes were not observed when comparing 5xFAD mice with wild type l…
Isolation of nuclei and downstream processing of cell-type-specific nuclei from micro-dissected mouse brain regions – techniques and caveats
2020
AbstractThe mammalian brain consists of several structurally and functionally distinct regions equipped with an equally complex cell-type system. Due to its relevance in uncovering disease mechanisms, the study of cell-type-specific molecular signatures of different brain regions has increased. The rapid evolution of newer and cheaper sequencing techniques has also boosted the interest in cell-type-specific epigenetic studies. In fact, the nucleus holds most of the cell’s epigenetic information and is quite resistant to tissue dissociation processes as compared to cells. As such, nuclei are continually preferred over cells for epigenetic studies. However, the isolation of nuclei from cells …