Publications by authors named "Nicholas J Eagles"
Article Synopsis
- The medial frontal cortex (mFC) and locus coeruleus (LC) are brain regions linked to cognitive functions like attention, memory, and decision-making, yet their molecular regulators remain unclear.
- Using chemogenetic stimulation in mice, the study found that activating LC neurons targeting the mFC led to increased gene transcription, especially in GABAergic neurons related to cognitive functions.
- The research highlights the role of specific gene expression as potential biomarkers for neuropsychiatric disorders like ADHD, schizophrenia, and Alzheimer's, aiming to inform treatments for cognitive and behavioral symptoms.
Article Synopsis
- - Maternal smoking during pregnancy has notable negative effects on the cognitive and behavioral development of offspring, with this study specifically comparing the impacts of nicotine and cigarette smoke on gene expression in developing brains.
- - Researchers found a significant number of differentially expressed genes (1,010 for nicotine and 4,165 for smoking) linked to prenatal exposure, indicating different neurodevelopmental pathways affected by each substance.
- - The findings suggest that while both prenatal nicotine exposure and maternal smoking have specific and overlapping effects on the developing brain, these effects are not replicated in the adult brain, highlighting developmental-stage sensitivity to smoke-related changes.
Article Synopsis
- Visium is a transcriptomics assay from 10x Genomics that struggles with overlapping tissue capture areas, needing better tools for combining data from multiple images effectively.
- A new R/Bioconductor package called visiumStitched has been developed to stitch these images together, allowing for more complex analysis while preserving data from overlapping areas.
- While visiumStitched simplifies the handling of multi-capture study designs, it does have some limitations regarding data accuracy when aligning with other reference atlases.
Article Synopsis
- The study investigates how neurodegenerative disorders, particularly Alzheimer's disease, affect brain microenvironments by analyzing brain tissue lesions associated with amyloid-β and hyperphosphorylated tau.
- Researchers used the advanced 10x Genomics Visium Spatial Proteogenomics platform to explore gene expression changes in post-mortem human brains, specifically in the inferior temporal cortex during late-stage Alzheimer's.
- The findings offer insights into molecular processes linked to brain pathology, provide a framework for analyzing spatial gene expression, and deliver accessible interactive resources for the scientific community to explore related datasets.
Article Synopsis
- Visium is a transcriptomics assay that allows researchers to analyze gene expression in tissue, but current software has limitations in merging more than two overlapping capture areas.* -
- A new R/Bioconductor package was developed to stitch images from overlapping capture areas and create visualizations, making it easier to analyze complex tissue structures without losing data.* -
- This solution enhances the flexibility of study designs involving multiple capture areas, paving the way for better spatial analysis while addressing issues with image alignment accuracy.*
Article Synopsis
- * Researchers used chemogenetics and RNA-sequencing to explore how stimulating the locus coeruleus affects gene expression in the frontal cortex, finding increased transcription of a specific gene.
- * Further investigations revealed that this gene's expression, which could influence attention-related behaviors, is particularly prominent in GABAergic neurons and varies by sex, suggesting potential therapeutic targets for attention disorders like ADHD, schizophrenia, and Alzheimer's disease.
Article Synopsis
- The study focuses on the molecular organization of the human neocortex, particularly the dorsolateral prefrontal cortex, using advanced spatial transcriptomic technologies.
- Researchers created a detailed neuroanatomical atlas that highlights different spatial domains based on gene expression patterns, moving beyond traditional histological layers.
- By integrating data from various sources, the team identified specific cell types and interactions linked to neuropsychiatric disorders, showing how these relate to spatial domains in the brain.
Article Synopsis
- Ancestral differences in genomic variation influence gene expression, with most studies focusing on European samples or adjusting for ancestry, rather than specifically examining it.
- This study explored how genetic ancestry impacts gene expression and DNA methylation in brain tissue from admixed Black American individuals, revealing ancestry-related genes primarily involved in immune response and vascular tissue rather than neurons.
- The identified ancestry-associated differentially expressed genes (DEGs) contribute to heritability for various conditions like ischemic stroke, Parkinson's, and Alzheimer's, highlighting significant differences in gene expression based on genetic ancestry and its implications for brain-related illnesses.
Article Synopsis
- - The study investigates the unique cell types within the human hippocampus, focusing on their roles in learning, memory, and cognition, using advanced methods like spatially-resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) on tissue from ten neurotypical adults.
- - Researchers employed non-negative matrix factorization (NMF) to analyze gene expression patterns across different neuronal cell types, discovering variations in excitatory and inhibitory responses within distinct spatial regions of the hippocampus.
- - The findings include the identification of molecular profiles for various hippocampal cell types and suggest these profiles’ relevance to learning capabilities, while making the resulting data publicly available for further research.
Article Synopsis
- High-resolution imaging techniques are enhancing our ability to observe biological systems in detail, but sharing and customizing these images can be challenging.
- Samui is a new web-based tool designed for fast and interactive visualization and annotation of large multidimensional images.
- The tool is compatible with images from Vizgen MERFISH and 10x Genomics Visium Spatial Gene Expression, and it's available for use at https://samuibrowser.com.
Article Synopsis
- - The study investigates the habenula (Hb) in relation to schizophrenia (SCZD) by examining its cell types and how their transcriptomic profiles differ in individuals with SCZD compared to healthy controls.
- - Researchers used advanced techniques like single nucleus RNA-sequencing and fluorescent hybridization to identify 17 distinct cell types in the human Hb and validated these findings.
- - They discovered 45 genes that are differentially expressed in the Hb of SCZD individuals, revealing significant genetic changes and providing new insights into the molecular basis of neuropsychiatric disorders.
Article Synopsis
- - The study focuses on improving the cellular deconvolution of bulk RNA-seq data using single-cell RNA-seq data to estimate cell type composition in diverse tissues, particularly in the human brain.
- - Researchers created a detailed multi-assay dataset from 22 postmortem human brain samples, employing various RNA-seq methods and comparing estimated cell proportions with actual measurements from other techniques.
- - The analysis identified specific deconvolution algorithms that performed best, revealing that factors like cell size and differences in gene quantification can impact the accuracy of these methods in reflecting true tissue composition.
Article Synopsis
- Bisulfite sequencing is essential for studying genomic methylation, crucial for understanding various health conditions like cancer, but processing the vast amounts of data generated is computationally intensive and time-consuming.
- * BiocMAP is a new workflow for methylation analysis that includes two modules: one for fast read alignment using GPU technology and another for data processing that can run even without a GPU, making it more accessible for researchers.
- * The pipeline is designed for efficient memory use and is compatible with R's Bioconductor, ensuring it can handle large WGBS datasets while promoting reproducibility across different computing setups.
Article Synopsis
- * Ancestry-associated differentially expressed genes (DEGs) are linked to immune response and vascular tissue, contributing to heritability for conditions like ischemic stroke, Parkinson's disease, and Alzheimer's disease, while showing less influence on psychiatric traits.
- * The study reveals that both genetic variation and environmental factors (like DNA methylation) shape gene expression differences across ancestry, impacting the risk of brain illnesses in diverse populations.
Article Synopsis
- High-resolution imaging techniques are improving our ability to observe biological systems, but sharing and customizing these large image datasets can be difficult.
- Samui is a new web-based tool designed for fast and interactive visualization and annotation of these images, allowing users to quickly explore their features.
- The tool has been tested with images from Vizgen MERFISH and 10x Genomics Visium platforms, and it's available for use with example datasets at https://samuibrowser.com.
Article Synopsis
- * Research revealed significant differences in gene expression related to antipsychotic drug toxicity in the human caudate nucleus, but no major differences in DNA methylation, echoing similarities found between schizophrenia cases and controls.
- * The study highlights varying gene expression changes in different brain regions and compares findings to a mouse model, noting some similarities but also significant differences, indicating that the effects of antipsychotics may stabilize over the long term.
Article Synopsis
- Neurons derived from human induced pluripotent stem cells (hiPSCs) are being studied to understand neuropsychiatric disorders, particularly schizophrenia (SCZ), focusing on how these cellular models relate to the patients' clinical features.
- Researchers analyzed neurons from 13 individuals with high genetic risk for SCZ and 15 neurotypical individuals, finding significant differences in their electrophysiological properties.
- This research suggests that specific neuronal functions can be linked to clinical symptoms, providing insights that could inform the development of new treatments for SCZ.
Article Synopsis
- DNA methylation (DNAm) is crucial for gene regulation and is influenced by environmental factors, and this study investigates its role in the brains of neurotypical individuals versus those with schizophrenia.
- Using whole-genome bisulfite sequencing on 344 brain tissue samples, researchers found that a significant proportion of genetic variation (like SNPs) affects local methylation levels, particularly around CpG and CpH sites.
- The study suggests that regions of the genome differentially affected by schizophrenia risk variants explain much of the heritability linked to schizophrenia, highlighting the potential of these epigenetic changes in understanding the disorder.
Background: RNA sequencing (RNA-seq) is a common and widespread biological assay, and an increasing amount of data is generated with it. In practice, there are a large number of individual steps a researcher must perform before raw RNA-seq reads yield directly valuable information, such as differential gene expression data. Existing software tools are typically specialized, only performing one step-such as alignment of reads to a reference genome-of a larger workflow.
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- DNA methylation (DNAm) plays a crucial role in regulating gene expression during the development of the prenatal brain, which is a complex and changing tissue.
- Researchers investigated methylation patterns at over 39 million sites in the prenatal cortex and discovered dynamic changes that are linked to nearby gene expression and associated with neuropsychiatric disorders.
- The study identified differences in DNAm between sexes during prenatal development and confirmed that the changes primarily involve CpG methylation, offering insights into both brain development and potential mental health issues later in life.