PT - JOURNAL ARTICLE AU - Eva Hulstaert AU - Annelien Morlion AU - Francisco Avila Cobos AU - Kimberly Verniers AU - Justine Nuytens AU - Eveline Vanden Eynde AU - Nurten Yigit AU - Jasper Anckaert AU - Anja Geerts AU - Pieter Hindryckx AU - Peggy Jacques AU - Guy Brusselle AU - Ken R. Bracke AU - Tania Maes AU - Thomas Malfait AU - Thierry Derveaux AU - Virginie Ninclaus AU - Caroline Van Cauwenbergh AU - Kristien Roelens AU - Ellen Roets AU - Dimitri Hemelsoet AU - Kelly Tilleman AU - Lieve Brochez AU - Scott Kuersten AU - Lukas Simon AU - Sebastian Karg AU - Alexandra Kautzky-Willers AU - Michael Leutner AU - Christa Nöhammer AU - Ondrej Slaby AU - Gary P. Schroth AU - Jo Vandesompele AU - Pieter Mestdagh TI - Charting extracellular transcriptomes in The Human Biofluid RNA Atlas AID - 10.1101/823369 DP - 2019 Jan 01 TA - bioRxiv PG - 823369 4099 - http://biorxiv.org/content/early/2019/11/05/823369.short 4100 - http://biorxiv.org/content/early/2019/11/05/823369.full AB - Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on plasma or serum, other biofluids may contain more informative RNA molecules, depending on the type of disease. Here, we present an unprecedented atlas of messenger, circular and small RNA transcriptomes of a comprehensive collection of 20 different human biofluids. By means of synthetic spike-in controls, we compared RNA content across biofluids, revealing a more than 10 000-fold difference in RNA concentration. The circular RNA fraction is increased in nearly all biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. In addition, a subset of biofluids, including stool, sweat, saliva and sputum, contains high levels of bacterial RNAs. Our atlas enables a more informed selection of the most relevant biofluid to monitor particular diseases. To verify the biomarker potential in these biofluids, four validation cohorts representing a broad spectrum of diseases were profiled, revealing numerous differential RNAs between case and control subjects. Taken together, our results reveal novel insights in the RNA content of human biofluids and may serve as a valuable resource for future biomarker studies.