Biology subjects

Ganglberger, F.

Publications and source records attributed to Ganglberger, F..

4 recordsLinked to original sources

bioRxiv2025

Glucocorticoid receptors mediate reprogramming of astrocytes in depression.

Psychiatric disorders are among the most pressing problems of the modern society, with various forms of depression affecting more than 300 millions of people worldwide. Dysfunction of glial cells has consistently been reported in major depressive disorder (MDD); however, no comprehensive resource detailing glial dysfunction is available. To provide insight into neurobiological mechanisms behind severe psychiatric symptoms, we performed transcriptional analysis of post-mortem samples from a subpopulation of suicide completers with previously reported glial abnormalities. We focused on BA25, a subregion of the prefrontal cortex prioritized for targeted medical interventions, due to its metabolic aberrations in disease. We found that a significant portion of genes deregulated in MDD is enriched in glia, with astrocyte-specific genes representing the highest fraction. Then we employed a novel protocol for enriching astrocytic nuclei to provide a detailed molecular signature of astrocytes in MDD. The analysis of the gene set revealed the glucocorticoid receptor (GR) as a key regulatory transcription factor. We found that astrocyte-specific elimination of the GR in mice largely prevented transcriptional, metabolic and behavioral changes elicited by chronic stress. We also demonstrated that regional manipulation of glutamate turnover in astrocytes suffices to elicit discrete traits of depressive-like behavior. Our data points to astrocytes as a key cellular site of convergence of multiple traits of depression and provide a resource for exploring novel targets for glia-focused therapeutic approaches.

neuroscience↗

bioRxiv2020

HieRFIT: Hierarchical Random Forest for Information Transfer

The emergence of single-cell RNA sequencing (scRNA-seq) has led to an explosion in novel methods to study biological variation among individual cells, and to classify cells into functional and biologically meaningful categories. Here, we present a new cell type projection tool, HieRFIT (Hierarchical Random Forest for Information Transfer), based on hierarchical random forests. HieRFIT uses a priori information about cell type relationships to improve classification accuracy, taking as input a hierarchical tree structure representing the class relationships, along with the reference data. We use an ensemble approach combining multiple random forest models, organized in a hierarchical decision tree structure. We show that our hierarchical classification approach improves accuracy and reduces incorrect predictions especially for inter-dataset tasks which reflect real life applications. We use a scoring scheme that adjusts probability distributions for candidate class labels and resolves uncertainties while avoiding the assignment of cells to incorrect types by labeling cells at internal nodes of the hierarchy when necessary. Using HieRFIT, we re-analyzed publicly available scRNA-seq datasets showing its effectiveness in cell type cross-projections with inter/intra-species examples. HieRFIT is implemented as an R package and it is available at (https://github.com/yasinkaymaz/HieRFIT/releases/tag/v1.0.0)

bioinformatics↗

bioRxiv2019

Molecular archaeology of the human brain

Mapping the origin of human cognitive traits typically relies on comparing behavioral or neuroanatomical features in human phylogeny. However, such studies rely on inferences from comparative relationships and do not incorporate neurogenetic information, as these approaches are restricted to experimentally accessible species. Here, we fused evolutionary genomics with human functional neuroanatomy to reconstruct the neurogenetic evolution of human brain functions more directly and comprehensively. Projecting genome-wide selection pressure (dN/dS ratios) in sets of chronologically ordered mammalian species onto the human brain reference space unmasked spatial patterns of cumulative neurogenetic selection and co-evolving brain networks from task-evoked functional MRI and functional neuroanatomy. Importantly, this evolutionary atlas allowed imputing functional features to archaic brains from extinct hominin genomes. These data suggest accelerated neurogenetic selection for language and verbal communication across all hominin lineages. In addition, the predictions identified strategic thought and decision making as the dominant traits that may have separated anatomically modern humans (AMH) from archaic hominins.

bioinformatics↗

bioRxiv2018

A Data Structure for real-time Aggregation Queries of Big Brain Networks

Recent advances in neuro-imaging allowed big brain-initiatives and consortia to create vast resources of brain data that can be mined by researchers for their individual projects. Exploring the relationship between genes, brain circuitry, and behavior is one of key elements of neuroscience research. This requires fusion of spatial connectivity data at varying scales, such as whole brain correlated gene expression, structural and functional connectivity. With ever-increasing resolution, those exceed the past state-of-the art in several orders of magnitude in size and complexity. Current analytical workflows in neuroscience involve time-consuming manual aggregation of the data and only sparsely incorporate spatial context to operate continuously on multiple scales. Incorporating techniques for handling big connectivity data is therefore a necessity.\n\nWe propose a data structure to explore heterogeneous neurobiological connectivity data for integrated visual analytics workflows. Aggregation Queries, i.e. the aggregated connectivity from, to or between brain areas allow experts the comparison of multimodal networks residing at different scales, or levels of hierarchically organized anatomical atlases. Executed on-demand on volumetric gene expression and connectivity data, they enable an interactive dissection of networks, with billions of edges, in real-time, and based on their spatial context. The data structure is optimized to be accessed directly from the hard disk, since connectivity of large-scale networks typically exceed the memory size of current consumer level PCs. This allows experts to embed and explore their own experimental data in the framework of public data resources without large-scale infrastructure.\n\nOur novel data structure outperforms state-of-the-art graph engines in retrieving connectivity of local brain areas experimentally. We demonstrate the application of our approach for neuroscience by analyzing fear-related functional neuroanatomy in mice. Further, we show its versatility by comparing multimodal brain networks linked to autism. Importantly, we achieve cross-species congruence in retrieving human psychiatric traits networks, which facilitates selection of neural substrates to be further studied in mouse models.

neuroscience↗