Profiling Extracellular Long RNA Transcriptome in Human Plasma and Extracellular Vesicles for Biomarker Discovery
Rodosthenis S. Rodosthenous,
Elizabeth Hutchins,
Rebecca Reiman,
Ashish S. Yeri,
Srimeenakshi Srinivasan,
Timothy G. Whitsett,
Ionita Ghiran,
Michael G. Silverman,
Louise C. Laurent,
Kendall Van Keuren-Jensen,
Saumya Das
Affiliations
Rodosthenis S. Rodosthenous
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Simches 3rd Floor, Boston, MA 02114, USA
Elizabeth Hutchins
Division of Neurogenomics, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Rebecca Reiman
Division of Neurogenomics, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Ashish S. Yeri
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Simches 3rd Floor, Boston, MA 02114, USA
Srimeenakshi Srinivasan
Department of Obstetrics, Gynecology, and Reproductive Sciences, Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Timothy G. Whitsett
Division of Neurogenomics, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Ionita Ghiran
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Michael G. Silverman
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Simches 3rd Floor, Boston, MA 02114, USA
Louise C. Laurent
Department of Obstetrics, Gynecology, and Reproductive Sciences, Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Kendall Van Keuren-Jensen
Division of Neurogenomics, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA; Corresponding author
Saumya Das
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Simches 3rd Floor, Boston, MA 02114, USA; Corresponding author
Summary: The recent discovery of extracellular RNAs in blood, including RNAs in extracellular vesicles (EVs), combined with low-input RNA-sequencing advances have enabled scientists to investigate their role in human disease. To date, most studies have been focusing on small RNAs, and methodologies to optimize long RNAs measurement are lacking. We used plasma RNA to assess the performance of six long RNA sequencing methods, at two different sites, and we report their differences in reads (%) mapped to the genome/transcriptome, number of genes detected, long RNA transcript diversity, and reproducibility. Using the best performing method, we further compare the profile of long RNAs in the EV- and no-EV-enriched RNA plasma compartments. These results provide insights on the performance and reproducibility of commercially available kits in assessing the landscape of long RNAs in human plasma and different extracellular RNA carriers that may be exploited for biomarker discovery.
