Methods for brain disease genetics using gene expression data of the healthy brain

Medical studies are rarely easy, and it is especially challenging to understand brain disease. Brains are highly complex organs, and it is, for instance, hard to see the relationships between behavioural change in a person and the changes in the connections among the billions of cells in the brain that cause this behavioural change. Many brain...

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...

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...

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...

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...