TY - JOUR
T1 - exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids
AU - Murillo, Oscar D.
AU - Thistlethwaite, William
AU - Rozowsky, Joel
AU - Subramanian, Sai Lakshmi
AU - Lucero, Rocco
AU - Shah, Neethu
AU - Jackson, Andrew R.
AU - Srinivasan, Srimeenakshi
AU - Chung, Allen
AU - Laurent, Clara D.
AU - Kitchen, Robert R.
AU - Galeev, Timur
AU - Warrell, Jonathan
AU - Diao, James A.
AU - Welsh, Joshua A.
AU - Hanspers, Kristina
AU - Riutta, Anders
AU - Burgstaller-Muehlbacher, Sebastian
AU - Shah, Ravi V.
AU - Yeri, Ashish
AU - Jenkins, Lisa M.
AU - Ahsen, Mehmet E.
AU - Cordon-Cardo, Carlos
AU - Dogra, Navneet
AU - Gifford, Stacey M.
AU - Smith, Joshua T.
AU - Stolovitzky, Gustavo
AU - Tewari, Ashutosh K.
AU - Wunsch, Benjamin H.
AU - Yadav, Kamlesh K.
AU - Danielson, Kirsty M.
AU - Filant, Justyna
AU - Moeller, Courtney
AU - Nejad, Parham
AU - Paul, Anu
AU - Simonson, Bridget
AU - Wong, David K.
AU - Zhang, Xuan
AU - Balaj, Leonora
AU - Gandhi, Roopali
AU - Sood, Anil K.
AU - Alexander, Roger P.
AU - Wang, Liang
AU - Wu, Chunlei
AU - Wong, David T.W.
AU - Galas, David J.
AU - Van Keuren-Jensen, Kendall
AU - Patel, Tushar
AU - Jones, Jennifer C.
AU - Das, Saumya
AU - Cheung, Kei Hoi
AU - Pico, Alexander R.
AU - Su, Andrew I.
AU - Raffai, Robert L.
AU - Laurent, Louise C.
AU - Roth, Matthew E.
AU - Gerstein, Mark B.
AU - Milosavljevic, Aleksandar
N1 - Funding Information:
This publication is part of the NIH Extracellular RNA Communication Consortium paper package and was supported by the NIH Common Fund’s exRNA Communication Program. This work was supported by a grant from the Common Fund of the NIH ( 5U54 DA036134 to A.M., D.J.G., and M.B.G. and UH2/UH3 TR000923 to D.T.W.W., and UH2/UH3 TR000901 to S.D.). This work was also supported in part by the NCI, NIH ( 5RO1 CA163849 to A.M.); the NIH Initiative for Maximizing Student Development ( 2R25 GM056929 to O.D.M.); the NIH ( UH3 TR000906 to S.S., C.D.L., and L.C.L.); the NIH ( 5U19 CA179512 , HL133575 , and P30 DK63720 to R.L.R.); the Intramural Research Program of the NCI, Center for Cancer Research, NIH (to J.A.W., L.M.J., and J.C.J.); NIH ( K23-HL127099 , R01-HL136685 , and R01-AG059729 to R.S; NIH ( UH3 TR000943 , R35 CA209904 , and CA217685 to A.K.S.); NIH (R01-HL 122547 to S.D.); the American Cancer Society Research Professor Award (to A.K.S.); and the Frank McGraw Memorial Chair in Cancer Research (to A.K.S.).
Funding Information:
This publication is part of the NIH Extracellular RNA Communication Consortium paper package and was supported by the NIH Common Fund's exRNA Communication Program. This work was supported by a grant from the Common Fund of the NIH (5U54 DA036134 to A.M. D.J.G. and M.B.G. and UH2/UH3 TR000923 to D.T.W.W. and UH2/UH3 TR000901 to S.D.). This work was also supported in part by the NCI, NIH (5RO1 CA163849 to A.M.); the NIH Initiative for Maximizing Student Development (2R25 GM056929 to O.D.M.); the NIH (UH3 TR000906 to S.S. C.D.L. and L.C.L.); the NIH (5U19 CA179512, HL133575, and P30 DK63720 to R.L.R.); the Intramural Research Program of the NCI, Center for Cancer Research, NIH (to J.A.W. L.M.J. and J.C.J.); NIH (K23-HL127099, R01-HL136685, and R01-AG059729 to R.S; NIH (UH3 TR000943, R35 CA209904, and CA217685 to A.K.S.); NIH (R01-HL 122547 to S.D.); the American Cancer Society Research Professor Award (to A.K.S.); and the Frank McGraw Memorial Chair in Cancer Research (to A.K.S.). Conceptualization, O.D.M. W.T. J.R. S.L.S. R.L. L.C.L. M.G. and A.M.; Methodology, O.D.M. W.T. S.L.S. K-H.C. and A.M.; Software, O.D.M. W.T. J.R. S.L.S. R.L. N.S. A.R.J. R.R.K. T.G. J.W. J.A.D. K.H. A.R. C.W. R.P.A. A.R.P. A.I.S. and A.M.; Validation, S.S. A.C. C.D.L. R.L.R. J.A.W. L.M.J. J.C.J. M.E.A. C.C.-C. N.D. S.M.G. J.T.S. G.S. A.K.T. B.H.W. K.K.Y. K.M.D. and L.C.L.; Formal Analysis, O.D.M. W.T. and A.M.; Investigation, O.M. D.T.W.W. D.J.G. R.V.S. A.Y. K.V.K.-J. L.W. T.P. K.M.D. J.F. C.M. P.N. A.R.P. B.S. D.K.W. X.Z. L.B. R.G. A.K.S. R.L.R. S.D. K.-H.C. A.R.P. A.I.S. L.M.J. L.C.L. M.E.R. M.B.G. and A.M.; Resources, A.R.J. R.L.R. L.C.L. and A.M.; Data Curation, W.T. S.L.S. N.S. and S.B.-M.; Writing – Original Draft, O.D.M. W.T. S.L.S. and A.M.; Writing – Review & Editing, O.D.M. W.T. J.R. S.L.S. M.E.R. and A.M.; Visualization, O.D.M. W.T. S.L.S. A.R.J. J.A.D. and A.M.; Supervision, J.R. L.C.L. and A.M.; Project Administration, M.E.R. M.B.G. and A.M.; Funding Acquisition, O.D.M. J.A.W. L.M.J. J.C.J. R.L.R. M.E.R. M.B.G. and A.M. Within the last 12 months, R.V.S. has received funds from Amgen (scientific advisory board), Myokardia (consulting), and Best Doctors (consulting). A.K.T. has received funds from Proxamo (scientific advisory board) and Siemens (scientific advisory board). R.V.S. is a co-inventor on a patent for exRNAs signatures of cardiac remodeling. All other authors declare no competing interests.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/4/4
Y1 - 2019/4/4
N2 - To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies. An extracellular RNA atlas from five human biofluids (serum, plasma, cerebrospinal fluid, saliva, and urine) reveals six extracellular RNA cargo types, including both vesicular and non-vesicular carriers.
AB - To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies. An extracellular RNA atlas from five human biofluids (serum, plasma, cerebrospinal fluid, saliva, and urine) reveals six extracellular RNA cargo types, including both vesicular and non-vesicular carriers.
KW - ERCC
KW - deconvolution
KW - exRNA
KW - exosomes
KW - extracellular RNA
KW - extracellular vesicles
KW - lipoproteins
KW - ribonucleoproteins
UR - http://www.scopus.com/inward/record.url?scp=85063266758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85063266758&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2019.02.018
DO - 10.1016/j.cell.2019.02.018
M3 - Article
C2 - 30951672
AN - SCOPUS:85063266758
SN - 0092-8674
VL - 177
SP - 463-477.e15
JO - Cell
JF - Cell
IS - 2
ER -