In many research disciplines, ordered lists are compared. One example is to compare a subset of all significant genes or proteins in a primary study to those in a replication study. Often, the top of ...the lists are compared using Venn diagrams, ore more precisely Euler diagrams (set diagrams showing logical relations between a finite collection of different sets). If different cohort sizes, different techniques or algorithms for evaluation were applied, a direct comparison of significant genes with a fixed threshold can however be misleading and approaches comparing lists would be more appropriate.
We developed DynaVenn, a web-based tool that incrementally creates all possible subsets from two or three ordered lists and computes for each combination a p-value for the overlap. Respectively, dynamic Venn diagrams are generated as graphical representations. Additionally an animation is generated showing how the most significant overlap is reached by backtracking. We demonstrate the improved performance of DynaVenn over an arbitrary cut-off approach on an Alzheimer's Disease biomarker set.
DynaVenn combines the calculation of the most significant overlap of different cohorts with an intuitive visualization of the results. It is freely available as a web service at http://www.ccb.uni-saarland.de/dynavenn.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The molecular causes and mechanisms of neurodegenerative diseases remain poorly understood. A growing number of single-cell studies have implicated various neural, glial, and immune cell ...subtypes to affect the mammalian central nervous system in many age-related disorders. Integrating this body of transcriptomic evidence into a comprehensive and reproducible framework poses several computational challenges. Here, we introduce ZEBRA, a large single-cell and single-nucleus RNA-seq database. ZEBRA integrates and normalizes gene expression and metadata from 33 studies, encompassing 4.2 million human and mouse brain cells sampled from 39 brain regions. It incorporates samples from patients with neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, and Multiple sclerosis, as well as samples from relevant mouse models. We employed scVI, a deep probabilistic auto-encoder model, to integrate the samples and curated both cell and sample metadata for downstream analysis. ZEBRA allows for cell-type and disease-specific markers to be explored and compared between sample conditions and brain regions, a cell composition analysis, and gene-wise feature mappings. Our comprehensive molecular database facilitates the generation of data-driven hypotheses, enhancing our understanding of mammalian brain function during aging and disease. The data sets, along with an interactive database are freely available at https://www.ccb.uni-saarland.de/zebra.
Graphical Abstract
Graphical Abstract
Abstract
Despite recent methodology and reference database improvements for taxonomic profiling tools, metagenomic assembly and genomic binning remain important pillars of metagenomic analysis ...workflows. In case reference information is lacking, genomic binning is considered to be a state-of-the-art method in mixed culture metagenomic data analysis. In this light, our previously published tool BusyBee Web implements a composition-based binning method efficient enough to function as a rapid online utility. Handling assembled contigs and long nanopore generated reads alike, the webserver provides a wide range of supplementary annotations and visualizations. Half a decade after the initial publication, we revisited existing functionality, added comprehensive visualizations, and increased the number of data analysis customization options for further experimentation. The webserver now allows for visualization-supported differential analysis of samples, which is computationally expensive and typically only performed in coverage-based binning methods. Further, users may now optionally check their uploaded samples for plasmid sequences using PLSDB as a reference database. Lastly, a new application programming interface with a supporting python package was implemented, to allow power users fully automated access to the resource and integration into existing workflows. The webserver is freely available under: https://www.ccb.uni-saarland.de/busybee.
Graphical Abstract
Graphical Abstract
BusyBee Web is a flexible online composition-based and reference-free metagenomic binning tool. Sending fasta sequences as input via API or web interface, the webserver computes binned sequences and provides a wide range of optional annotations.
Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is ...poorly understood. We recently identified serum response factor (SRF)-a transcription factor known to regulate expression of actin and actin regulators in other cell types-as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.
Abstract
Arm selection, the preferential expression of a 3′ or 5′ mature microRNA (miRNA), is a highly dynamic and tissue-specific process. Time-dependent expression shifts or switches between the ...arms are also relevant for human diseases. We present miRSwitch, a web server to facilitate the analysis and interpretation of arm selection events. Our species-independent tool evaluates pre-processed small non-coding RNA sequencing (sncRNA-seq) data, i.e. expression matrices or output files from miRNA quantification tools (miRDeep2, miRMaster, sRNAbench). miRSwitch highlights potential changes in the distribution of mature miRNAs from the same precursor. Group comparisons from one or several user-provided annotations (e.g. disease states) are possible. Results can be dynamically adjusted by choosing from a continuous range of highly specific to very sensitive parameters. Users can compare potential arm shifts in the provided data to a human reference map of pre-computed arm shift frequencies. We created this map from 46 tissues and 30 521 samples. As case studies we present novel arm shift information in a Alzheimer’s disease biomarker data set and from a comparison of tissues in Homo sapiens and Mus musculus. In summary, miRSwitch offers a broad range of customized arm switch analyses along with comprehensive visualizations, and is freely available at: https://www.ccb.uni-saarland.de/mirswitch/.
Hashimoto's thyroiditis is the principal aetiology of hypothyroidism with presence of anti-thyroperoxidase antibodies (anti-TPO). The association between anti-TPO and foeto-placental complications ...has been observed in previous studies. To go further in the understanding, the current study compares the level of anti-TPO in maternal blood and in the cord blood of her fetus at the moment of childbirth to demonstrate the passage of anti-TPO through the placenta barrier.
This study was realised in a maternity ward located in the Northern district of Paris, France from 2006 to 2007. Women with normal pregnancy were included in a first study and only women with no abnormal thyroid dosage at baseline and tested positive with anti-TPO were prospectively enrolled. Maternal blood samples were collected in the third trimester and at the arrival to the ward when patients came to deliver. After delivery, cord blood sample was collected. Pearson's correlation coefficient was computed. 5941 patients delivered in the ward during the study, 33 pregnant women were included. We found a correlation between the anti-TPO levels in maternal and in the cord blood of their fetus with a correlation coefficient of 0.98 and a p-value<0.001.
This is the first demonstration of the free passage through the placental barrier of anti-TPO from the mother to the fetus at the moment of childbirth. These findings can be extrapolated all along pregnancy and open the door to a direct action of the anti-TPO on fetus and to a possible action on the fetal thyroid.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The present experiment aimed to explore the interindividual variability in chemosensory abilities among the elderly population. The chemosensory abilities of 559 subjects, aged from 65 to 99 years, ...were evaluated. Various categories of the elderly, including people who were living at home either without or with assistance, and people who were living in a nursing home, were interviewed. The results revealed that 43% of the sample presented well-preserved chemosensory abilities, whereas 21% of the participants presented a moderate impairment. Of the sample, 33% presented well-preserved olfactory abilities but strong impairment in gustatory abilities and 3% were nearly anosmic but remained able to perceive the salty taste, demonstrating that gustation and olfaction were not systematically damaged simultaneously. The results showed a link between the level of dependence (free living vs. living at home with help vs. nursing home) and chemosensory abilities, independently of the age effect. These results strengthen the hypothesis that the impairment of chemosensory abilities is not only an effect of age per se; rather, it is related to events that are associated with aging. Factors that lead to increased dependence (such as poor health) also lead to an impairment in chemosensory performance.
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