@article{4ba3241bd01d4fd7bc66cac6184d9d6b,
title = "Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation",
abstract = "Poor reproducibility within and across studies arising from lack of knowledge regarding the performance of extracellular RNA (exRNA) isolation methods has hindered progress in the exRNA field. A systematic comparison of 10 exRNA isolation methods across 5 biofluids revealed marked differences in the complexity and reproducibility of the resulting small RNA-seq profiles. The relative efficiency with which each method accessed different exRNA carrier subclasses was determined by estimating the proportions of extracellular vesicle (EV)-, ribonucleoprotein (RNP)-, and high-density lipoprotein (HDL)-specific miRNA signatures in each profile. An interactive web-based application (miRDaR) was developed to help investigators select the optimal exRNA isolation method for their studies. miRDar provides comparative statistics for all expressed miRNAs or a selected subset of miRNAs in the desired biofluid for each exRNA isolation method and returns a ranked list of exRNA isolation methods prioritized by complexity, expression level, and reproducibility. These results will improve reproducibility and stimulate further progress in exRNA biomarker development. A systematic comparison of 10 extracellular RNA isolation methods across 5 biofluids will aid researchers in selecting optimal approaches for individual studies with the overall goal of enhancing reliability and reproducibility for a rapidly growing field.",
keywords = "extracellular RNA, extracellular vesicles, lipoprotein, ribonucleoprotein",
author = "Srimeenakshi Srinivasan and Ashish Yeri and Cheah, {Pike See} and Allen Chung and Kirsty Danielson and {De Hoff}, Peter and Justyna Filant and Laurent, {Clara D.} and Laurent, {Lucie D.} and Rogan Magee and Courtney Moeller and Murthy, {Venkatesh L.} and Parham Nejad and Anu Paul and Isidore Rigoutsos and Rodosthenis Rodosthenous and Shah, {Ravi V.} and Bridget Simonson and Cuong To and David Wong and Yan, {Irene K.} and Xuan Zhang and Leonora Balaj and Breakefield, {Xandra O.} and George Daaboul and Roopali Gandhi and Jodi Lapidus and Eric Londin and Tushar Patel and Raffai, {Robert L.} and Sood, {Anil K.} and Alexander, {Roger P.} and Saumya Das and Laurent, {Louise C.}",
note = "Funding Information: This publication is part of the NIH Extracellular RNA Communication Consortium paper package and was supported by the NIH Common Fund{\textquoteright}s exRNA Communication Program. We would like to thank Aileen Fernando, Fabian Flores, and the UCSD Clinical and Translational Research Institute for assisting us with collection of the standardized plasma and serum samples used in this study. We would like to thank Thomas Touboul for assisting us with collection of hESC supernatant for this study. This study was supported by the Extracellular RNA Communication Consortium funded by the NIH Common Fund ( NIH UH3TR000906 [S.S., P.D.H., C.D.L., L.D.L., C.M., C.T., L.C.L.], NIH U19179563 [P.S.C., X.Z., L.B., X.O.B.], NIH UH3TR000901 [K.D., R.V.S., B.S., S.D., J.L.]; NIH UH3TR000943 [A.K.S.], NIH UH3TR000890 [P.N., A.P., R.G.]), NIH UH3TR000884 [I.K.Y., T.P.], NIH U19CA179512 [R.L.R.]; NIH U54DA036134 [R.P.A.]) and other funding sources (NIH P01069246 [P.S.C., X.Z., L.B., X.O.B.]; NIH RO1HL122547 [K.D., R.V.S., B.S., S.D., J.L.]; NIH R35CA209904 and CA217685 , the American Cancer Society Research Professor Award, and the Frank McGraw Memorial Chair in Cancer Research [A.K.S.]; NIH K23 HL127099 [R.V.S.]; NIH R01HL133575 [R.L.R.]; NIH T32 HD007203 [S.S.]; NIH/NHLBI HL141424 [I.R.]; NIH/NCI CA195204 [E.L., I.R., R.M.]; Thomas Jefferson University Institutional Funds [E.L., I.R., R.M.]). Funding Information: S.D. is a founding member of Dyrnamix, which did not play any role in this study and has a patent on extracellular RNA biomarkers for cardiac remodeling. Over the past 12 months, R.V.S. has received funds from Amgen (scientific advisory board), Myokardia (consulting), and Best Doctors (consulting). R.V.S. is a co-inventor on a patent for ex-RNAs signatures of cardiac remodeling. R.G. has been employed by Sanofi Genzyme since September 2017, working on a multiple sclerosis treatment. A.K.S. has the following interests: Advisory board member for Kiyatec and Merck; research funding from M-Trap; stock holder for Biopath; patents for EGFL6 antibodies and siRNA delivery systems. ",
year = "2019",
month = apr,
day = "4",
doi = "10.1016/j.cell.2019.03.024",
language = "English (US)",
volume = "177",
pages = "446--462.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}