@article{ef95663fc7804c3bbd53f06a255dfd3e,
title = "Discovery and Verification of Extracellular miRNA Biomarkers for Non-invasive Prediction of Pre-eclampsia in Asymptomatic Women",
abstract = "Development of effective prevention and treatment strategies for pre-eclampsia is limited by the lack of accurate methods for identification of at-risk pregnancies. We performed small RNA sequencing (RNA-seq) of maternal serum extracellular RNAs (exRNAs) to discover and verify microRNAs (miRNAs) differentially expressed in patients who later developed pre-eclampsia. Sera collected from 73 pre-eclampsia cases and 139 controls between 17 and 28 weeks gestational age (GA), divided into separate discovery and verification cohorts, are analyzed by small RNA-seq. Discovery and verification of univariate and bivariate miRNA biomarkers reveal that bivariate biomarkers verify at a markedly higher rate than univariate biomarkers. The majority of verified biomarkers contain miR-155-5p, which has been reported to mediate the pre-eclampsia-associated repression of endothelial nitric oxide synthase (eNOS) by tumor necrosis factor alpha (TNF-α). Deconvolution analysis reveals that several verified miRNA biomarkers come from the placenta and are likely carried by placenta-specific extracellular vesicles.",
keywords = "biomarkers, bivariate, extracellular RNA, extracellular vesicle, maternal serum, miR-155-5p, miRNA, placenta, pre-eclampsia, small RNA-seq",
author = "{The PAPR Study Consortium} and Srimeenakshi Srinivasan and Ryan Treacy and Tiffany Herrero and Richelle Olsen and Leonardo, {Trevor R.} and Xuan Zhang and Peter DeHoff and Cuong To and Poling, {Lara G.} and Aileen Fernando and Sandra Leon-Garcia and Katharine Knepper and Vy Tran and Morgan Meads and Jennifer Tasarz and Aishwarya Vuppala and Soojin Park and Laurent, {Clara D.} and Tony Bui and Cheah, {Pike See} and {Tabitha Overcash}, Rachael and Ramos, {Gladys A.} and Hilary Roeder and Ionita Ghiran and Mana Parast and Boggess, {Kim A.} and Saade, {George R.} and Sullivan, {Scott A.} and Markenson, {Glenn R.} and Iams, {Jay D.} and Coonrod, {Dean V.} and Pereira, {Leonardo M.} and Esplin, {M. Sean} and Cousins, {Larry M.} and Lam, {Garrett K.} and Hoffman, {Matthew K.} and Breakefield, {Xandra O.} and Lueth, {Amir J.} and Rust, {Sharon R.} and Dufford, {Max T.} and Fox, {Angela C.} and Hickok, {Durlin E.} and Julja Burchard and Boniface, {J. Jay} 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 the Harvard Brain Bank and Lifesharing for adult tissue samples and Luc Laurent for illustrating the graphical abstract. This work was funded by NIH UH3TR000906 (S.S., T.H., R.T., R.O., T.R.L., X.Z., C.T., A.F., S.L.-G., K.K., V.T., M.M., J.T., A.V., S.P., R.T.O., G.A.R., H.R., D.E.H., J.B., J.J.B., and L.C.L.) and NIH U01HL126494 (S.S., X.Z., P.D., L.G.P., C.D.L., T.B., X.O.B., and L.C.L.). 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. We would like to thank the Harvard Brain Bank and Lifesharing for adult tissue samples and Luc Laurent for illustrating the graphical abstract. This work was funded by NIH UH3TR000906 (S.S. T.H. R.T. R.O. T.R.L. X.Z. C.T. A.F. S.L.-G. K.K. V.T. M.M. J.T. A.V. S.P. R.T.O. G.A.R. H.R. D.E.H. J.B. J.J.B. and L.C.L.) and NIH U01HL126494 (S.S. X.Z. P.D. L.G.P. C.D.L. T.B. X.O.B. and L.C.L.). Conceptualization, L.C.L. J.J.B. and J.B.; Software and Formal Analysis, J.B. R.T. A.J.L. and C.T.; Investigation, S.S. T.H. R.T.O, T.R.L. X.Z. P.D. L.G.P. A.F. S.L.-G. K.K. V.T. M.M. M.T.D. C.D.L. T.B. and P.S.C.; Resources, I.G. and The PAPR Study Consortium; Data Curation, S.P. R.T.O. G.A.R. H.R. J.T. and A.V.; Writing ? Original Draft, S.S. R.T. T.H. L.G.P. J.B. and L.C.L.; Writing ? Review & Editing, S.S. R.T. J.B. D.E.H. J.J.B. and L.C.L.; Visualization, R.T. J.B. and L.G.P.; Supervision, L.C.L. J.J.B. J.B. D.E.H. and X.O.B.; Project Administration, D.E.H. A.C.F. S.R.R. and M.P.; Funding Acquisition, L.C.L. L.C.L. is a site PI for the Sera Prognostics TREETOP study. J.B.B. J.B. D.E.H. A.C.F. M.T.D. S.R.R. A.J.L. and R.T. are employees and shareholders in Sera Prognostics. Sera Prognostics has filed a provisional patent application (United States Provisional Application no. 62/777,576) on the findings presented in this manuscript. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = may,
day = "19",
doi = "10.1016/j.xcrm.2020.100013",
language = "English (US)",
volume = "1",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "2",
}