bioRxiv Science⌕ Search

Biology subjects

Barre, A.

Publications and source records attributed to Barre, A..

2 recordsLinked to original sources

SeuratIntegrate: an R package to facilitate the use of integration methods with Seurat

MotivationIntegrating multiple datasets has become an increasingly common task in scRNA-seq analysis. The advent of single-cell atlases adds further complexity to this task, as they often involve combining data with complex, nested batch effects - such as those arising from multiple studies, organs or disease states. Accurate data integration is essential to distinguish cell types with sufficient granularity, thereby reflecting true biological patterns, and to create reliable reference datasets for the community. In this context, the latest version of Seurat (v5) introduced a multi-layered object structure to facilitate the integration of scRNA-seq datasets in a unified manner. However, the panel of available batch-correction methods remains limited to five algorithms within Seurat, restricting users from accessing a broader diversity of available tools, particularly Python-based methods. Furthermore, no existing R tool assists the user in making an informed decision in selecting the most appropriate integration approach. ResultsTo overcome these challenges, we developed SeuratIntegrate, an open source R package that extends Seurats functionality. SeuratIntegrate supports eight integration methods, incorporating both R- and Python-based tools, and enables performance evaluation of integration through several scoring methods. This functionality allows for a more versatile and informed integration process. AvailabilitySeuratIntegrate is available at https://github.com/cbib/Seurat-Integrate/. The package is released under the MIT License.

bioinformatics↗

D--hydroxybutyrate stabilizes the hippocampal CA3-CA1 circuit during acute insulin resistance.

1.The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D--hydroxybutyrate (D-Hb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-Hb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential (AP) properties, while D-Hb rescued neuronal functions associated with axonal conduction, synchronization, and LTP. 2. Significance statementThis study investigates the impact of acute insulin resistance on the functionality of the hippocampal circuit and the potential protective effects of ketone body supplementation. By inhibiting GLUT4 receptors to induce acute insulin resistance, we reveal several detrimental changes caused by impaired neuronal glucose uptake. These changes include impairments in synaptic activity, axonal conduction, and neuronal firing properties. The study further examines the distinctive effects of acute insulin resistance and the rescue agent D-{beta}Hb on synaptic activity, long-term potentiation, axonal conduction, synchronization, and neuronal firing. By shedding light on neuronal responses during insulin resistance, this investigation advances our understanding of neurological disorders associated with hypometabolism and highlights the potential therapeutic value of D-{beta}Hb.

neuroscience↗