CyTOFmerge: integrating mass cytometry data across multiple panels

Motivation: High-dimensional mass cytometry (CyTOF) allows the simultaneous measurement of multiple cellular markers at single-cell level, providing a comprehensive view of cell compositions.<br/>However, the power of CyTOF to explore the full heterogeneity of a biological sample at the singlecell level is currently limited by the number of...

How metabolic state may regulate fear: Presence of metabolic receptors in the fear circuitry

Metabolic status impacts on the emotional brain to induce behavior that maintains energy balance. While hunger suppresses the fear circuitry to promote explorative food-seeking behavior, satiety or obesity may increase fear to prevent unnecessary risk-taking. Here we aimed to unravel which metabolic factors, that transfer information about...

RNA sequencing data integration reveals an miRNA interactome of osteoarthritis cartilage

Objective To uncover the microRNA (miRNA) interactome of the osteoarthritis (OA) pathophysiological process in the cartilage.<br/>Methods We performed RNA sequencing in 130 samples (n=35 and n=30 pairs for messenger RNA (mRNA) and miRNA, respectively) on macroscopically preserved and lesioned OA cartilage from the same patient and performed...

Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington’s Disease

Cytosine-adenine-guanine (CAG) repeat expansions in the coding regions of nine polyglutamine (polyQ) genes (HTT, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATN1, AR, and TBP) are the cause of several neurodegenerative diseases including Huntington’s disease (HD), six different spinocerebellar ataxias (SCAs), dentatorubral-pallidoluysian atrophy, and...

Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a muscular dystrophy with high incidence of learning and behavioural problems and is associated with neurodevelopmental disorders. To gain more insights into the role of dystrophin in this cognitive phenotype, we performed a comprehensive analysis of the expression patterns of dystrophin isoforms across...

BrainScope: Interactive visual exploration of the spatial and temporal human brain transcriptome

Spatial and temporal brain transcriptomics has recently emerged as an invaluable data source for molecular neuroscience. The complexity of such data poses considerable challenges for analysis and visualization. We present BrainScope: A web portal for fast, interactive visual exploration of the Allen Atlases of the adult and developing human...

Brain transcriptome atlases: A computational perspective

The immense complexity of the mammalian brain is largely reflected in the underlying molecular signatures of its billions of cells. Brain transcriptome atlases provide valuable insights into gene expression patterns across different brain areas throughout the course of development. Such atlases allow researchers to probe the molecular mechanisms...

Cortical Spreading Depression Causes Unique Dysregulation of Inflammatory Pathways in a Transgenic Mouse Model of Migraine

Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation (‘FHM1 R192Q mice’) exhibit an increased susceptibility to cortical spreading...

Pan-cancer subtyping in a 2D-map shows substructures that are driven by specific combinations of molecular characteristics

The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a...

Interpreting a migraine GWAS using gene expression in healthy human brain

Migraine is a common brain disorder, with a heritability of 50%. Genome-wide association studies have identified several loci, but interpretation remains challenging. We integrated migraine GWAS data with spatial gene expression data of adult brains from the Allen Human Brain Atlas, to identify specific brain regions and molecular pathways...

Shared Pathways Among Autism Candidate Genes Determined by Co-expression Network Analysis of the Developing Human Brain Transcriptome

Autism spectrum disorder (ASD) is a neurodevelopmental syndrome known to have a significant but complex genetic etiology. Hundreds of diverse genes have been implicated in ASD; yet understanding how many genes, each with disparate function, can all be linked to a single clinical phenotype remains unclear. We hypothesized that understanding...

Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains...

Genome-wide coexpression of steroid receptors in the mouse brain: identifying signaling pathways and functionally coordinated regions

Steroid hormones coordinate the activity of many brain regions by binding to nuclear receptors that act as transcription factors. This study uses genome-wide correlation of gene expression in the mouse brain to discover (i) brain regions that respond in a similar manner to particular steroids, (ii) signaling pathways that are used in a steroid...

Visualizing the spatial gene expression organization in the brain through non-linear similarity embeddings

The Allen Brain Atlases enable the study of spatially resolved, genome-wide gene expression patterns across the mammalian brain. Several explorative studies have applied linear dimensionality reduction methods such as Principal Component Analysis (PCA) and classical Multi-Dimensional Scaling (cMDS) to gain insight into the spatial organization...

Co-expression Network Analysis of the Developing Human Brain Implicates Synaptogenesis and Mitochondrial Function as Central Mechanisms in Autism

We analyzed the spatial-temporal co-expression relationships of 455 genes previously implicated in Autism spectrum disorder (ASD) using the BrainSpan transcriptome atlas. Understanding how the heterogenous set of ASD-related genes contribute to normal brain development helps identifying cellular/molecular processes which are commonly disrupted...