Project description:Genome-wide gene expression studies may provide a comprehensive insight in gene activities and biological pathways differing between individuals and tissues (even closely related tissues building complex organs such as the brain). Our research addressed both kinds of gene expression variation – between brain regions and between individuals – by expression profiling in brain tissues derived from eight brain regions and blood from 12 vervet monkeys (Chlorocebus aethiops sabaeus). We employed the non-human primate model to assure tissue quality and to enhance the probability of precise dissection of the brain tissues, which is difficult to realize in human subjects. We characterized brain regional differences in gene expression levels which may relate to specific functions of brain tissues including disease symptoms affecting specific brain regions. We focused on inter-individual variability of brain transcript levels in different regions that correlates well between blood and brain tissues and therefore could be further reliably studied in easily accessible blood samples. Applying very stringent transcript selection criteria including 1). considerable similarities between brain and blood tissues, 2). consistent repeat measurements in blood, 3). higher inter-individual than intra-individual variability and 4). detection in all tissue samples, allowed us to identify transcripts in which inter-individual variation in brain expression profiles indicates possible genetic factors regulating gene transcript levels. High heritabilities of these transcript levels indicated that our approach focusing on transcripts showing higher inter-individual variability than intra-individual variability identifies transcripts with a strong genetic component.
Project description:Genetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an 'epigenetic signature' of early-life experiences. Here, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular–metabolic enzymes, ion channels and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate related transcription factors, indicating their potential upregulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function.
Project description:We aimed at assessing the extent of gene expression inter/intra-histotype heterogeneity and ITH in four different pediatric cancer histotypes, analysing multiple samples of each single tumor mass.
Project description:In order to accurately evaluate methods for dealing with inter-individual differences in cord blood cell type in DNA methylation data, matched samples with both DNAm profiles and detailed FACS counts are necessary.
Project description:We report the application of single molecule-based sequencing technology in combination with MBD affinity purifcation (MAP-seq) to generate methylation maps in a panel of human brain samples. Here we assay the methylation status of the human genome in eight distinct brain regions from three individuals in addition to a further thirty six hippocampal samples. The cerebellum was a consistent outlier compared to all other regions, showing over 16,000 differentially methylated regions (DMRs). Unexpectedly, the sequence properties of hypo- and hyper- methylated domains in cerebellum were distinct. In contrast we found very few DMRs that could distinguish between regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable, however with the exception of cerebellum, DNA methylation patterns are more similar between different brain regions from the same individual, than they are for a single brain region between different individuals.
Project description:We report single-cell RNA sequencing of 57,114 cells from 8 meningioma samples and 2 dura samples, which are used to analyze the inter- and intra-meningioma heterogeneity across DNA methylation groups.
Project description:Genome wide DNA methylation profiles of various human brain regions (cerebellum, occipital lobe, etc). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. The dataset includes 130 samples. Multiple brain regions were assessed per subject. The goal was to evaluate the effect of HIV infection on DNA methylation levels. Genome wide DNA methylation profiles of various brain regions from HIV positive and negative subjects. The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 480,000 CpGs. Dataset included 130 samples: 99 samples from HIV+ subjects and 31 samples from HIV- subjects.