Extracellular Genomic Loci (exGLs) and associated annotations¶

Previous versions of the exRNA Atlas focused on distinct aspects of exRNA biology. The first version mapped exRNA to its vesicular (exosomes and other extracellular vesicles) and non-vesicular (lipoproteins, RNPs, and other specific classes particles) carriers in human biofluids, and the second version further deepened our understanding of exRNA carriers by identifying extracellular RNA-binding proteins (exRBPs) that associate with exRNA fragments in the extracellular space. One key limitation of those early maps was that the exRNA expression was quantitatively ascertained using GENCODE and ENCODE/ENCORE genome annotations. While being useful as initial stepping stones toward understanding exRNA biology, these annotations heavily constrained the insights that could be gained about the role of exRNA in human biology.

The most glaring gap in exRNA biology was the lack of information about the loci that are transcribed into exRNA. With the completion of the Extracellular RNA Communication Consoritum and aggregation of the uniformly processed exRNA profiles in the Atlas, we here addressed this question for the first time. We provide the first map of extracellular Genomic Loci (exGLs) transcribed and exported as extracellular RNA into human plasma, serum, urine, cerebrospinal fluid (CSF), and saliva. These five biofluids were selected because they represent the largest number of samples in the exRNA Atlas, comprising 6,532 smRNA-seq profiles from 60 datasets. For those biofluids, we identify biofluid-specific exGLs de novo, independent of previous genome annotations. This study identifies >30 million unique extracellular RNA genomic loci (exGLs) covering >18% of the human genome expressing exRNA.

All exGLs are viewable via UCSC Genome Browser track hub

ExRNA Atlas datasets used to generate exGLs are available here

To support standardized referencing of these exGLs, we developed the exGL identification service, which assigns unique identifiers (exGLids) to each exGL. exGLids and associated annotations—such as expression depth, gene or regulatory element overlap, and biofluid distribution—can be accessed via User Interface or programmatically via APIs or as TSVs