An RNA seq-based reference landscape of human normal and neoplastic brain

Abstract

In order to better understand the relationship between normal and neoplastic brain, we combined five publicly available large-scale datasets, correcting for batch effects and applying Uniform Manifold Approximation and Projection (UMAP) to RNA-seq data. We assembled a reference Brain-UMAP including 702 adult gliomas, 802 pediatric tumors and 1409 healthy normal brain samples, which can be utilized to investigate the wealth of information obtained from combining several publicly available datasets to study a single organ site. Normal brain regions and tumor types create distinct clusters and because the landscape is generated by RNA seq, comparative gene expression profiles and gene ontology patterns are readily evident. To our knowledge, this is the first meta-analysis that allows for comparison of gene expression and pathways of interest across adult gliomas, pediatric brain tumors, and normal brain regions. We provide access to this resource via the open source, interactive online tool Oncoscape, where the scientific community can readily visualize clinical metadata, gene expression patterns, gene fusions, mutations, and copy number patterns for individual genes and pathway over this reference landscape.

WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma

“…S7B ). To examine WDR5 expression in more detail, we queried WDR5 and WRAD complex member expression in RNA sequencing data through a recently reported “Brain-UMAP” ( Arora et al 2023 ). Batch-corrected log 2 -normalized gene expression data from different uniformly processed pipelines, including 702 adult glioma samples from The Cancer Genome Atlas (TCGA), 270 adult glioma samples from the Chinese Glioma Genome Atlas (CGGA), 1409 healthy normal brain samples from the Genotype–Tissue Expression Project (GTEx) across 12 GTEx-defined brain regions, and 802 pediatric tumor samples from the Children's Brain Tumor Network (CBTN), were used to generate the Brain-UMAP.…”