Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas

Eva Hulstaert¹, Annelien Morlion², Francisco Avila Cobos², Kimberly Verniers², Justine Nuytens², Eveline Vanden Eynde², Nurten Yigit², Jasper Anckaert², Anja Geerts³, Pieter Hindryckx³, Peggy Jacques⁴, Guy Brusselle⁵, Ken R Bracke⁵, Tania Maes⁵, Thomas Malfait⁵, Thierry Derveaux⁶, Virginie Ninclaus⁶, Caroline Van Cauwenbergh⁶, Kristien Roelens⁷, Ellen Roets⁷, Dimitri Hemelsoet⁸, Kelly Tilleman⁹, Lieve Brochez¹⁰, Scott Kuersten¹¹, Lukas M Simon¹², Sebastian Karg¹³, Alexandra Kautzky-Willers¹⁴, Michael Leutner¹⁴, Christa Nöhammer¹⁵, Ondrej Slaby¹⁶, Roméo Willinge Prins¹⁷, Jan Koster¹⁷, Steve Lefever², Gary P Schroth¹¹, Jo Vandesompele², Pieter Mestdagh¹⁸

Affiliations

¹ Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Department of Dermatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
² Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium.
³ Department of Gastroenterology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁴ Department of Rheumatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium; VIB Inflammation Research Center, Ghent University, Technologiepark 71, 9052 Ghent, Belgium.
⁵ Department of Respiratory Medicine, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁶ Department of Ophthalmology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁷ Department of Obstetrics, Women's Clinic, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁸ Department of Neurology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁹ Department of Reproductive Medicine, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
¹⁰ OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Department of Dermatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
¹¹ Illumina, San Diego, CA, USA.
¹² University of Texas Health Science Center, School of Biomedical Informatics, Center for Precision Health, Houston, TX, USA.
¹³ Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
¹⁴ Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna, Vienna, Austria.
¹⁵ Austrian Institute of Technology, Center for Health and Bioresources, Molecular Diagnostics, Vienna, Austria.
¹⁶ Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic; Department of Pathology, University Hospital Brno, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
¹⁷ Department of Oncogenomics, Amsterdam University Medical Centers (AUMC), University of Amsterdam, Amsterdam, the Netherlands.
¹⁸ Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium. Electronic address: pieter.mestdagh@ugent.be.

PMID: 33378673
DOI: 10.1016/j.celrep.2020.108552

Free article

Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas

Eva Hulstaert et al. Cell Rep. 2020.

Free article

. 2020 Dec 29;33(13):108552.

doi: 10.1016/j.celrep.2020.108552.

Authors

Affiliations

¹ Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Department of Dermatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
² Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium.
³ Department of Gastroenterology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁴ Department of Rheumatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium; VIB Inflammation Research Center, Ghent University, Technologiepark 71, 9052 Ghent, Belgium.
⁵ Department of Respiratory Medicine, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁶ Department of Ophthalmology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁷ Department of Obstetrics, Women's Clinic, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁸ Department of Neurology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
⁹ Department of Reproductive Medicine, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
¹⁰ OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; Department of Dermatology, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium.
¹¹ Illumina, San Diego, CA, USA.
¹² University of Texas Health Science Center, School of Biomedical Informatics, Center for Precision Health, Houston, TX, USA.
¹³ Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany.
¹⁴ Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism, Unit of Gender Medicine, Medical University of Vienna, Vienna, Austria.
¹⁵ Austrian Institute of Technology, Center for Health and Bioresources, Molecular Diagnostics, Vienna, Austria.
¹⁶ Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic; Department of Pathology, University Hospital Brno, Brno, Czech Republic; Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
¹⁷ Department of Oncogenomics, Amsterdam University Medical Centers (AUMC), University of Amsterdam, Amsterdam, the Netherlands.
¹⁸ Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium; OncoRNALab, Cancer Research Institute Ghent (CRIG), Ghent University, C. Heymanslaan 10, 9000 Ghent, Belgium. Electronic address: pieter.mestdagh@ugent.be.

PMID: 33378673
DOI: 10.1016/j.celrep.2020.108552

Abstract

Extracellular RNAs present in biofluids have emerged as potential biomarkers for disease. Where most studies focus on blood-derived fluids, other biofluids may be more informative. We present an atlas of messenger, circular, and small RNA transcriptomes of a comprehensive collection of 20 human biofluids. By means of synthetic spike-in controls, we compare RNA content across biofluids, revealing a 10,000-fold difference in concentration. The circular RNA fraction is increased in most biofluids compared to tissues. Each biofluid transcriptome is enriched for RNA molecules derived from specific tissues and cell types. Our atlas enables an 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. Spike-normalized data are publicly available in the R2 web portal for further exploration.

Keywords: RNA sequencing; biofluids; biomarker; cell-free RNA; circular RNA; extracellular RNA; liquid biopsy; messenger RNA; small RNA.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas

Affiliations

Charting Extracellular Transcriptomes in The Human Biofluid RNA Atlas

Authors

Affiliations

Abstract

Conflict of interest statement

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MeSH terms

Substances

LinkOut - more resources

Full Text Sources

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