Associations of Circulating Extracellular Rnas with Myocardial Remodeling and Heart Failure
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Supplementary Online Content Shah RV, Rong J, Larson MG, et al. Associations of circulating extracellular RNAs with myocardial remodeling and heart failure. Published online August 8, 2018. JAMA Cardiology. doi:10.1001/jamacardio.2018.2371 eMethods. Pathway analysis. eReferences. eTable 1. List of circulating extracellular RNAs included in the study. eTable 2. Age- and sex-adjusted linear models for the association between cardiac structural parameters and extracellular RNAs. eTable 3. Survival analysis for incident HF, Models 1 and 2. eFigure 1. Data overlay on pathway representation of top TGF-beta Signaling Pathway hit. eFigure 2. Data overlay on network representation of top TGF-beta Signaling Pathway hit extended with interactions to hypertension genes. This supplementary material has been provided by the authors to give readers additional information about their work. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eMethods. Pathway analysis Gene targets of candidate exRNAs were extracted from experimentally validated interactions in miRTarBase version 6.1 using Target Interaction Finder.1 The output included an xGMML network file that was imported into Cytoscape for subnetwork analysis and data visualization.2 Sub-networks were generated using topological filters to exclude targets of just one exRNA in order to focus on targets with a greater number of candidate exRNA associations and more supporting evidence. Functional characterization of targeted genes was performed using the bioinformatics tool, Enrichr,3 which provided significance scores for enriched processes and pathways from Gene Ontology and WikiPathways4 and disease terms from OMIM in a tabular format. eReferences 1. Riutta A, Hanspers K, Pico AR. Target interaction finder. GitHub Repository. 2017 2017. 2. Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research. Nov 2003;13(11):2498-2504. 3. Kuleshov MV, Jones MR, Rouillard AD, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic acids research. Jul 08 2016;44(W1):W90-97. 4. Kutmon M, Riutta A, Nunes N, et al. WikiPathways: capturing the full diversity of pathway knowledge. Nucleic acids research. Jan 04 2016;44(D1):D488-494. © 2018 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 eTable 1. List of circulating extracellular RNAs included in the study. N specifies number of participants in whom ex-RNA quantification was possible. Mean specifies mean PCR cycle value. SD specifies standard deviation. Variable N Mean SD piRNA-12151 2751 18.32 1.07 piRNA-54042 2723 16.01 1.61 piRNA-54043 2720 16.05 1.63 miR-16-5p 2716 13.54 1.48 piRNA-2888 2708 16.30 1.57 miR-486-5p 2706 14.83 1.36 miR-126-5p 2698 16.75 1.17 miR-342-3p 2678 17.76 1.10 miR-126-3p 2669 16.07 1.20 miR-30a-5p 2666 16.88 1.20 miR-223-3p 2665 14.72 1.57 miR-451a 2664 11.95 1.89 miR-92a-3p 2664 15.33 1.20 miR-21-5p 2662 15.85 1.40 miR-25-3p 2660 16.94 1.35 miR-19b-3p 2657 15.08 1.29 miR-30e-5p 2654 17.00 1.16 miR-26a-5p 2653 17.28 1.30 miR-191-5p 2652 15.99 1.85 miR-23a-3p 2651 15.88 1.18 miR-221-3p 2648 17.74 1.27 miR-26b-5p 2648 17.40 1.32 miR-30d-5p 2648 17.17 1.37 miR-24-3p 2646 16.50 1.17 miR-15b-5p 2645 16.95 1.16 miR-150-5p 2638 17.22 1.48 miR-19a-3p 2638 15.75 1.32 miR-320a 2634 18.52 1.18 miR-20a-5p 2633 16.83 1.28 miR-484 2633 17.87 1.22 miR-22-3p 2629 16.51 1.33 miR-29a-3p 2627 16.85 1.21 miR-29c-3p 2625 16.86 1.20 snoRNA-1409 2625 18.30 1.44 miR-122-5p 2622 17.90 1.52 miR-93-5p 2612 17.86 1.24 miR-17-5p 2610 17.82 1.23 miR-106b-5p 2609 17.68 1.24 miR-146a-5p 2609 18.42 1.16 snoRNA-1408 2608 18.45 1.42 miR-151b- 2605 18.83 1.13 miR-27a-3p 2603 17.46 1.63 miR-195-5p 2584 16.51 3.14 miR-1260a 2572 18.41 1.30 miR-199a-3p 2561 18.62 1.27 snoRNA-1441 2560 19.36 1.13 Downloaded From: https://jamanetwork.com/ on 09/28/2021 © 2018 American Medical Association. All rights reserved. miR-148a-3p 2556 18.32 1.45 miR-148b-3p 2547 18.55 1.34 miR-222-3p 2531 19.13 1.15 miR-101-3p 2528 18.77 1.23 miR-142-5p 2513 18.68 1.33 piRNA-52468 2510 19.27 1.25 miR-4446-3p 2509 19.27 1.32 snoRNA-1277 2505 18.83 1.34 miR-140-3p 2502 19.19 1.15 miR-28-3p 2471 17.32 1.88 miR-145-5p 2466 19.43 1.18 miR-23b-3p 2458 19.37 1.13 miR-151a-5p 2452 19.37 1.17 miR-185-5p 2448 19.01 1.30 miR-423-5p 2441 19.30 1.20 miR-4433b-5p 2428 19.29 1.21 miR-194-5p 2417 18.51 1.49 miR-186-5p 2412 19.39 1.13 miR-128-3p 2407 19.15 1.34 miR-197-3p 2392 19.93 0.95 miR-130a-3p 2366 19.49 1.17 miR-125a-5p 2338 19.38 1.14 miR-30b-5p 2327 19.65 1.12 miR-125b-5p 2324 19.76 1.06 miR-27b-3p 2312 19.17 1.32 let-7a-5p 2302 19.43 1.24 miR-574-3p 2278 19.54 1.33 let-7b-5p 2277 19.43 1.25 miR-30c-5p 2268 19.75 1.09 miR-103a-3p 2241 19.59 1.16 miR-29b-3p 2237 19.61 1.16 let-7d-5p 2230 19.52 1.23 let-7g-5p 2194 19.44 1.25 miR-99b-5p 2187 19.77 1.24 miR-424-5p 2163 19.16 1.33 miR-6511b-3p 2159 19.93 1.11 miR-18a-5p 2143 19.88 1.07 piRNA-40304 2143 19.08 1.61 let-7i-5p 2136 19.49 1.34 miR-423-3p 2136 19.92 1.11 piRNA-48383 2135 19.60 1.44 let-7d-3p 2129 19.92 1.06 piRNA-43376 2124 19.16 1.60 snoRNA-1460 2087 19.39 1.41 miR-652-3p 2080 19.02 2.00 miR-144-3p 2072 19.01 1.53 piRNA-20101 2051 19.93 1.16 miR-192-5p 2043 19.94 1.11 miR-363-3p 2040 19.53 1.18 miR-28-5p 2025 19.56 1.36 miR-425-5p 2017 19.53 1.22 Downloaded From: https://jamanetwork.com/ on 09/28/2021 © 2018 American Medical Association. All rights reserved. miR-766-3p 2010 19.63 1.05 snoRNA-1401 2010 19.86 1.32 let-7c-5p 1997 20.17 1.01 miR-664b-3p 1997 16.37 3.56 piRNA-57322 1982 19.91 1.12 miR-320b 1978 16.96 3.01 miR-99a-5p 1947 19.53 1.21 miR-532-3p 1935 19.54 1.49 miR-1260b 1912 20.31 0.95 miR-106b-3p 1896 18.08 1.81 miR-494-3p 1880 17.07 2.31 miR-885-5p 1880 19.71 1.34 piRNA-49916 1847 20.09 1.02 miR-15a-5p 1845 20.24 1.00 miR-744-5p 1845 14.11 3.64 let-7f-5p 1830 20.19 1.04 snoRNA-1210 1823 18.57 2.61 miR-139-5p 1793 20.04 1.02 miR-433-3p 1791 20.39 1.12 miR-7977 1779 20.34 1.07 miR-181a-2-3p 1768 19.39 1.50 piRNA-51124 1768 19.78 1.35 piRNA-33872 1736 20.27 1.05 piRNA-58596 1712 20.35 1.03 piRNA-57403 1703 19.84 1.36 miR-301b-3p 1683 18.20 1.96 miR-1246 1676 17.97 2.11 piRNA-33384 1669 20.60 0.83 miR-204-5p 1662 9.72 3.69 piRNA-1340 1634 19.55 1.74 miR-362-3p 1607 20.20 1.13 piRNA-232882 1566 20.27 0.99 piRNA-2962 1561 20.12 1.15 miR-32-5p 1544 20.09 1.20 miR-146b-5p 1531 20.16 1.16 miR-30a-3p 1522 18.03 1.88 piRNA-31112 1507 19.69 1.45 miR-324-5p 1497 20.25 0.85 miR-532-5p 1495 19.50 1.72 miR-432-5p 1478 20.17 1.15 miR-340-5p 1476 20.41 0.99 miR-1271-5p 1463 19.42 1.01 miR-365a-3p 1458 20.42 1.06 snoRNA-1387 1451 20.43 1.13 miR-374b-5p 1450 20.41 1.05 miR-199b-5p 1438 19.89 1.27 piRNA-243353 1426 20.59 1.01 miR-3613-3p 1416 18.41 1.60 piRNA-41647 1408 20.41 0.98 miR-376c-3p 1407 20.38 1.04 miR-4770 1400 20.50 1.05 Downloaded From: https://jamanetwork.com/ on 09/28/2021 © 2018 American Medical Association.