exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Oscar D. Murillo; William Thistlethwaite; Joel Rozowsky; Sai Lakshmi Subramanian; Rocco Lucero; Neethu Shah; Andrew R. Jackson; Srimeenakshi Srinivasan; Allen Chung; Clara D. Laurent; Robert R. Kitchen; Timur Galeev; Jonathan Warrell; James A. Diao; Joshua A. Welsh; Kristina Hanspers; Anders Riutta; Sebastian Burgstaller-Muehlbacher; Ravi V. Shah; Ashish Yeri; Lisa M. Jenkins; Mehmet E. Ahsen; Carlos Cordon-Cardo; Navneet Dogra; Stacey M. Gifford; Joshua T. Smith; Gustavo Stolovitzky; Ashutosh K. Tewari; Benjamin H. Wunsch; Kamlesh K. Yadav; Kirsty M. Danielson; Justyna Filant; Courtney Moeller; Parham Nejad; Anu Paul; Bridget Simonson; David K. Wong; Xuan Zhang; Leonora Balaj; Roopali Gandhi; Anil K. Sood; Roger P. Alexander; Liang Wang; Chunlei Wu; David T.W. Wong; David J. Galas; Kendall Van Keuren-Jensen; Tushar Patel; Jennifer C. Jones; Saumya Das; Kei Hoi Cheung; Alexander R. Pico; Andrew I. Su; Robert L. Raffai; Louise C. Laurent; Matthew E. Roth; Mark B. Gerstein; Aleksandar Milosavljevic

doi:10.1016/j.cell.2019.02.018

exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

Oscar D. Murillo, William Thistlethwaite, Joel Rozowsky, Sai Lakshmi Subramanian, Rocco Lucero, Neethu Shah, Andrew R. Jackson, Srimeenakshi Srinivasan, Allen Chung, Clara D. Laurent, Robert R. Kitchen, Timur Galeev, Jonathan Warrell, James A. Diao, Joshua A. Welsh, Kristina Hanspers, Anders Riutta, Sebastian Burgstaller-Muehlbacher, Ravi V. Shah, Ashish YeriLisa M. Jenkins, Mehmet E. Ahsen, Carlos Cordon-Cardo, Navneet Dogra, Stacey M. Gifford, Joshua T. Smith, Gustavo Stolovitzky, Ashutosh K. Tewari, Benjamin H. Wunsch, Kamlesh K. Yadav, Kirsty M. Danielson, Justyna Filant, Courtney Moeller, Parham Nejad, Anu Paul, Bridget Simonson, David K. Wong, Xuan Zhang, Leonora Balaj, Roopali Gandhi, Anil K. Sood, Roger P. Alexander, Liang Wang, Chunlei Wu, David T.W. Wong, David J. Galas, Kendall Van Keuren-Jensen, Tushar Patel, Jennifer C. Jones, Saumya Das, Kei Hoi Cheung, Alexander R. Pico, Andrew I. Su, Robert L. Raffai, Louise C. Laurent, Matthew E. Roth, Mark B. Gerstein, Aleksandar Milosavljevic

Gastroenterology and Hepatology

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	463-477.e15
Journal	Cell
Volume	177
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2019.02.018
State	Published - Apr 4 2019

Keywords

ERCC
deconvolution
exRNA
exosomes
extracellular RNA
extracellular vesicles
lipoproteins
ribonucleoproteins

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2019.02.018

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Murillo, O. D., Thistlethwaite, W., Rozowsky, J., Subramanian, S. L., Lucero, R., Shah, N., Jackson, A. R., Srinivasan, S., Chung, A., Laurent, C. D., Kitchen, R. R., Galeev, T., Warrell, J., Diao, J. A., Welsh, J. A., Hanspers, K., Riutta, A., Burgstaller-Muehlbacher, S., Shah, R. V., ... Milosavljevic, A. (2019). exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids. Cell, 177(2), 463-477.e15. https://doi.org/10.1016/j.cell.2019.02.018

Murillo, OD, Thistlethwaite, W, Rozowsky, J, Subramanian, SL, Lucero, R, Shah, N, Jackson, AR, Srinivasan, S, Chung, A, Laurent, CD, Kitchen, RR, Galeev, T, Warrell, J, Diao, JA, Welsh, JA, Hanspers, K, Riutta, A, Burgstaller-Muehlbacher, S, Shah, RV, Yeri, A, Jenkins, LM, Ahsen, ME, Cordon-Cardo, C, Dogra, N, Gifford, SM, Smith, JT, Stolovitzky, G, Tewari, AK, Wunsch, BH, Yadav, KK, Danielson, KM, Filant, J, Moeller, C, Nejad, P, Paul, A, Simonson, B, Wong, DK, Zhang, X, Balaj, L, Gandhi, R, Sood, AK, Alexander, RP, Wang, L, Wu, C, Wong, DTW, Galas, DJ, Van Keuren-Jensen, K, Patel, T, Jones, JC, Das, S, Cheung, KH, Pico, AR, Su, AI, Raffai, RL, Laurent, LC, Roth, ME, Gerstein, MB & Milosavljevic, A 2019, 'exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids', Cell, vol. 177, no. 2, pp. 463-477.e15. https://doi.org/10.1016/j.cell.2019.02.018

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title = "exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids",

abstract = "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.",

keywords = "ERCC, deconvolution, exRNA, exosomes, extracellular RNA, extracellular vesicles, lipoproteins, ribonucleoproteins",

author = "Murillo, {Oscar D.} and William Thistlethwaite and Joel Rozowsky and Subramanian, {Sai Lakshmi} and Rocco Lucero and Neethu Shah and Jackson, {Andrew R.} and Srimeenakshi Srinivasan and Allen Chung and Laurent, {Clara D.} and Kitchen, {Robert R.} and Timur Galeev and Jonathan Warrell and Diao, {James A.} and Welsh, {Joshua A.} and Kristina Hanspers and Anders Riutta and Sebastian Burgstaller-Muehlbacher and Shah, {Ravi V.} and Ashish Yeri and Jenkins, {Lisa M.} and Ahsen, {Mehmet E.} and Carlos Cordon-Cardo and Navneet Dogra and Gifford, {Stacey M.} and Smith, {Joshua T.} and Gustavo Stolovitzky and Tewari, {Ashutosh K.} and Wunsch, {Benjamin H.} and Yadav, {Kamlesh K.} and Danielson, {Kirsty M.} and Justyna Filant and Courtney Moeller and Parham Nejad and Anu Paul and Bridget Simonson and Wong, {David K.} and Xuan Zhang and Leonora Balaj and Roopali Gandhi and Sood, {Anil K.} and Alexander, {Roger P.} and Liang Wang and Chunlei Wu and Wong, {David T.W.} and Galas, {David J.} and {Van Keuren-Jensen}, Kendall and Tushar Patel and Jones, {Jennifer C.} and Saumya Das and Cheung, {Kei Hoi} and Pico, {Alexander R.} and Su, {Andrew I.} and Raffai, {Robert L.} and Laurent, {Louise C.} and Roth, {Matthew E.} and Gerstein, {Mark B.} and Aleksandar Milosavljevic",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = apr,

day = "4",

doi = "10.1016/j.cell.2019.02.018",

language = "English (US)",

volume = "177",

pages = "463--477.e15",

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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

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

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exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids

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Keywords

ASJC Scopus subject areas

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