BBBomics-Human Blood Brain Barrier Transcriptomics Hub

Blood-brain barrier (BBB) is a monolayer of endothelial cells that line brain capillaries. The BBB protects brain by blocking the entry of harmful substances from blood and shielding the brain from peripheral fluctuations in hormones, fatty acids, and electrolytes. In addition, the BBB effectively clears brain metabolites and serves as a major conduit for the delivery of crucial nutrients and growth factors needed for proper brain function. Owing to these critical responsibilities, any functional and structural impairment of the BBB may result in severe pathophysiological consequences in the brain. BBB dysfunction is implicated in several neurodegenerative disorders including Alzheimer's disease (Carmeliet and De Strooper, 2012), Parkinson's disease (Kortekaas et al., 2005), and cerebrovascular diseases (Yang and Rosenberg, 2011) such as cerebral amyloid angiopathy, stroke, and vascular dementia. Hence, the research community has been actively investigating the cerebrovascular contributions to neurological diseases with major emphasis on the BBB. The success of these efforts is heavily dependent upon the availability of reliable in vitro as well as in vivo BBB models. Polarized monolayers of human cerebrovascular endothelial cells (hCMEC/D3) described in the current work serves as one such in vitro model that can be easily cultured and manipulated in the lab (Poller et al., 2008; Vu et al., 2009; Weksler et al., 2013). The barrier properties and the expression of several classes of receptors, transporters, and enzymes in hCMEC/D3 cells have been previously investigated (Urich et al., 2012; Lopez-Ramirez et al., 2013, 2014; Bamji-Mirza et al., 2014; Ilina et al., 2015; Naik et al., 2015; Sajja and Cucullo, 2015). Thus, far, the genomic data for hCMEC/D3 cell lines have been generated using array-based approaches (Lopez-Ramirez et al., 2013). However, a comprehensive transcriptomic landscape of hCMEC/D3 cells, which is required for investigating molecular mechanisms using sophisticated computational biology approaches, is not currently available. Next-generation sequencing technology unveils the full potential of systems biology approaches to resolve cellular and molecular interaction networks that regulate the functional integrity of the BBB. Such a panoramic view of the interaction networks could enable us to isolate key players regulating a physiological process and investigate how they are affected in various diseases. To our knowledge, we are the first group to generate deep RNA sequencing and microRNA sequencing of a human BBB cell line. This data report describes BBBomics hub as a comprehensive portal for BBB transcriptomics data, obtained by sequencing mRNA (mRNA-seq) and microRNA (miRNA-seq) of polarized hCMEC/D3 cell monolayers. This data encompasses coding (gene expression, alternate splice forms, expressed single nucleotide variants -eSNVs) and non-coding (microRNA, LincRNA, circular RNA) counts that are easily accessible through BBBomics hub database. We also superimposed the RNA-seq coding data on 285 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which include canonical, non-canonical, and/or atypical pathways retrievable using BBBomics hub. The data is easily accessible and freely available at http://bioinformaticstools.mayo. edu/bbbomics/.