Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity

Controlled human infections provide opportunities to study the interaction between the immune system and malaria parasites, which is essential for vaccine development. Here, we compared immune signatures of malaria-naive Europeans and of Africans with lifelong malaria exposure using mass cytometry, RNA sequencing and data integration, before...

Eleven grand challenges in single-cell data science

The recent boom in microfluidics and combinatorial indexing strategies, combined with low sequencing costs, has empowered single-cell sequencing technology. Thousands-or even millions-of cells analyzed in a single experiment amount to a data revolution in single-cell biology and pose unique data science problems. Here, we outline eleven...

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

The molecular mechanisms underlying caudal-to-rostral progression of Lewy body pathology in Parkinson’s disease remain poorly understood. Here, we identified transcriptomic signatures across brain regions involved in Braak Lewy body stages in non-neurological adults from the Allen Human Brain Atlas. Among the genes that are indicative of...

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...

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...

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...

Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are...

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...

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...