Brendo: an open resource for uniquely transcribed genes in brain endothelial cells

Abstract

The blood-brain barrier (BBB) plays a critical role in central nervous system homeostasis, yet comprehensive transcriptional profiling of brain microvascular endothelial cells (BMECs) remains limited. Leveraging the increasing availability of publicly accessible bulk RNA sequencing (RNA-seq) datasets, we developed an integrated analytical framework to identify genes selectively enriched in BMECs compared to endothelial cells (ECs) from other tissues. To address the substantial batch effects inherent to multi-source bulk RNA-seq data, we combined two differential expression strategies, rank aggregation methods, and extensive quality controls. Our analysis incorporated EC samples from 16 different tissues and employed robust statistical workflows to mitigate technical confounders while preserving biologically meaningful signals. Validation using known BBB markers and independent proteomic evidence confirmed the reliability of our approach. We present Brendo (Brain Endothelial Open Resource), an open-access web platform providing searchable, filterable, and downloadable data on differentially expressed genes in BMECs. Brendo enables an in-depth exploration of brain endothelial gene expression and offers broader applications across vascular biology by supporting cross-tissue EC comparisons. The workflow described is adaptable to other biological contexts, promoting the systematic reuse of public bulk RNA-seq datasets for target discovery. Collectively, this resource provides a foundation for advancing BBB-targeted therapeutic strategies and highlights the value of open data integration in transcriptomic research.