{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:19:55Z","timestamp":1781702395084,"version":"3.54.5"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T00:00:00Z","timestamp":1695081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017023","name":"Paul G. Allen Frontiers Group","doi-asserted-by":"publisher","award":["17DIA33820024"],"award-info":[{"award-number":["17DIA33820024"]}],"id":[{"id":"10.13039\/100017023","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37\u201339\u00a0weeks) from women with normal pregnancies (n\u2009=\u20095) or carrying fetuses with CDH (n\u2009=\u20095). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, in the MSP\u2013RON signaling in macrophages pathway and in networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Differences in selected proteins, namely pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin-3 were validated by orthogonal testing using ELISA in larger cohorts and showed statistically significant differences aiding in the diagnosis and prediction of CDH. The findings provide potential tools for clinical management of CDH.<\/jats:p>","DOI":"10.1038\/s41598-023-42576-2","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T09:02:27Z","timestamp":1695114147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic\u00a0fluid"],"prefix":"10.1038","volume":"13","author":[{"given":"Sumit","family":"Bhutada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Tran-Lundmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Kramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Conner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M.","family":"Lowry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Blackstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Frenckner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Mesas-Burgos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneel S.","family":"Apte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,19]]},"reference":[{"issue":"1","key":"42576_CR1","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41572-022-00362-w","volume":"8","author":"A Zani","year":"2022","unstructured":"Zani, A. et al. Congenital diaphragmatic hernia. Nat. Rev. Dis. Primers 8(1), 37. https:\/\/doi.org\/10.1038\/s41572-022-00362-w (2022).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"42576_CR2","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2021.1926448","author":"VS Gupta","year":"2021","unstructured":"Gupta, V. S. et al. Birth weight predicts patient outcomes in infants who undergo congenital diaphragmatic hernia repair. J. Matern. Fetal Neonatal Med. https:\/\/doi.org\/10.1080\/14767058.2021.1926448 (2021).","journal-title":"J. Matern. Fetal Neonatal Med."},{"issue":"10297","key":"42576_CR3","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/s0140-6736(21)00767-4","volume":"398","author":"NJ Wright","year":"2021","unstructured":"Wright, N. J. et al. Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: A multicentre, international, prospective cohort study. Lancet 398(10297), 325\u2013339. https:\/\/doi.org\/10.1016\/s0140-6736(21)00767-4 (2021).","journal-title":"Lancet"},{"issue":"4","key":"42576_CR4","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.jpedsurg.2020.06.003","volume":"56","author":"VS Gupta","year":"2021","unstructured":"Gupta, V. S. et al. Cornelia de Lange syndrome and congenital diaphragmatic hernia. J. Pediatr. Surg. 56(4), 697\u2013699. https:\/\/doi.org\/10.1016\/j.jpedsurg.2020.06.003 (2021).","journal-title":"J. Pediatr. Surg."},{"issue":"1","key":"42576_CR5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1002\/bdra.20098","volume":"73","author":"M van Dooren","year":"2005","unstructured":"van Dooren, M., Tibboel, D. & Torfs, C. The co-occurrence of congenital diaphragmatic hernia, esophageal atresia\/tracheoesophageal fistula, and lung hypoplasia. Birth Defects Res. A Clin. Mol. Teratol. 73(1), 53\u201357. https:\/\/doi.org\/10.1002\/bdra.20098 (2005).","journal-title":"Birth Defects Res. A Clin. Mol. Teratol."},{"issue":"1","key":"42576_CR6","doi-asserted-by":"publisher","first-page":"151168","DOI":"10.1053\/j.semperi.2019.07.007","volume":"44","author":"N Patel","year":"2020","unstructured":"Patel, N., Massolo, A. C. & Kipfmueller, F. Congenital diaphragmatic hernia-associated cardiac dysfunction. Semin. Perinatol. 44(1), 151168. https:\/\/doi.org\/10.1053\/j.semperi.2019.07.007 (2020).","journal-title":"Semin. Perinatol."},{"issue":"1","key":"42576_CR7","doi-asserted-by":"publisher","first-page":"151171","DOI":"10.1053\/j.semperi.2019.07.010","volume":"44","author":"LE Hollinger","year":"2020","unstructured":"Hollinger, L. E. & Buchmiller, T. L. Long term follow-up in congenital diaphragmatic hernia. Semin. Perinatol. 44(1), 151171. https:\/\/doi.org\/10.1053\/j.semperi.2019.07.010 (2020).","journal-title":"Semin. Perinatol."},{"issue":"6","key":"42576_CR8","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1002\/uog.13271","volume":"43","author":"M Bebbington","year":"2014","unstructured":"Bebbington, M. et al. Comparison of ultrasound and magnetic resonance imaging parameters in predicting survival in isolated left-sided congenital diaphragmatic hernia. Ultrasound Obstet. Gynecol. 43(6), 670\u2013674. https:\/\/doi.org\/10.1002\/uog.13271 (2014).","journal-title":"Ultrasound Obstet. Gynecol."},{"issue":"1","key":"42576_CR9","doi-asserted-by":"publisher","first-page":"51163","DOI":"10.1053\/j.semperi.2019.07.002","volume":"44","author":"AG Cordier","year":"2020","unstructured":"Cordier, A. G., Russo, F. M., Deprest, J. & Benachi, A. Prenatal diagnosis, imaging, and prognosis in Congenital Diaphragmatic Hernia. Semin. Perinatol. 44(1), 51163. https:\/\/doi.org\/10.1053\/j.semperi.2019.07.002 (2020).","journal-title":"Semin. Perinatol."},{"issue":"1","key":"42576_CR10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1053\/j.sempedsurg.2012.10.006","volume":"22","author":"T Victoria","year":"2013","unstructured":"Victoria, T., Danzer, E. & Adzick, N. S. Use of ultrasound and MRI for evaluation of lung volumes in fetuses with isolated left congenital diaphragmatic hernia. Semin. Pediatr. Surg. 22(1), 30\u201336. https:\/\/doi.org\/10.1053\/j.sempedsurg.2012.10.006 (2013).","journal-title":"Semin. Pediatr. Surg."},{"issue":"4","key":"42576_CR11","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1021\/pr060543t","volume":"6","author":"JE Michaels","year":"2007","unstructured":"Michaels, J. E. et al. Comprehensive proteomic analysis of the human amniotic fluid proteome: gestational age-dependent changes. J. Proteome Res. 6(4), 1277\u20131285. https:\/\/doi.org\/10.1021\/pr060543t (2007).","journal-title":"J. Proteome Res."},{"issue":"1","key":"42576_CR12","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41598-021-04050-9","volume":"12","author":"G Bhatti","year":"2022","unstructured":"Bhatti, G. et al. The amniotic fluid proteome changes with gestational age in normal pregnancy: A cross-sectional study. Sci. Rep. 12(1), 601. https:\/\/doi.org\/10.1038\/s41598-021-04050-9 (2022).","journal-title":"Sci. Rep."},{"issue":"5","key":"42576_CR13","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/j.jprot.2009.12.009","volume":"73","author":"AK Anagnostopoulos","year":"2010","unstructured":"Anagnostopoulos, A. K. et al. Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome foetuses. J. Proteomics 73(5), 943\u2013950. https:\/\/doi.org\/10.1016\/j.jprot.2009.12.009 (2010).","journal-title":"J. Proteomics"},{"key":"42576_CR14","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.placenta.2019.10.010","volume":"89","author":"J Cen","year":"2020","unstructured":"Cen, J. et al. Comparative proteome analysis of amniotic fluids and placentas from patients with idiopathic polyhydramnios. Placenta 89, 67\u201377. https:\/\/doi.org\/10.1016\/j.placenta.2019.10.010 (2020).","journal-title":"Placenta"},{"issue":"24","key":"42576_CR15","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1080\/14767058.2019.1702953","volume":"34","author":"HN Peiris","year":"2021","unstructured":"Peiris, H. N. et al. Preterm labor is characterized by a high abundance of amniotic fluid prostaglandins in patients with intra-amniotic infection or sterile intra-amniotic inflammation. J. Matern. Fetal Neonatal. Med. 34(24), 4009\u20134024. https:\/\/doi.org\/10.1080\/14767058.2019.1702953 (2021).","journal-title":"J. Matern. Fetal Neonatal. Med."},{"issue":"8","key":"42576_CR16","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1002\/pmic.200300455","volume":"3","author":"F Vuadens","year":"2003","unstructured":"Vuadens, F. et al. Identification of biologic markers of the premature rupture of fetal membranes: Proteomic approach. Proteomics 3(8), 1521\u20131525. https:\/\/doi.org\/10.1002\/pmic.200300455 (2003).","journal-title":"Proteomics"},{"issue":"3","key":"42576_CR17","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1021\/pr501120x","volume":"14","author":"MC Mimmi","year":"2015","unstructured":"Mimmi, M. C. et al. Phospholipid profile of amniotic fluid in ovine model of congenital diaphragmatic hernia (CDH): The effect of fetal tracheal occlusion. J Proteome Res. 14(3), 1465\u20131471. https:\/\/doi.org\/10.1021\/pr501120x (2015).","journal-title":"J Proteome Res."},{"issue":"11","key":"42576_CR18","doi-asserted-by":"publisher","first-page":"4502","DOI":"10.1021\/acs.jproteome.5b00131","volume":"14","author":"A Croitor-Sava","year":"2015","unstructured":"Croitor-Sava, A. et al. High-resolution (1)H NMR spectroscopy discriminates amniotic fluid of fetuses with congenital diaphragmatic hernia from healthy controls. J. Proteome Res. 14(11), 4502\u20134510. https:\/\/doi.org\/10.1021\/acs.jproteome.5b00131 (2015).","journal-title":"J. Proteome Res."},{"issue":"8","key":"42576_CR19","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1074\/mcp.M700090-MCP200","volume":"6","author":"CK Cho","year":"2007","unstructured":"Cho, C. K., Shan, S. J., Winsor, E. J. & Diamandis, E. P. Proteomics analysis of human amniotic fluid. Mol. Cell Proteomics 6(8), 1406\u20131415. https:\/\/doi.org\/10.1074\/mcp.M700090-MCP200 (2007).","journal-title":"Mol. Cell Proteomics"},{"key":"42576_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jprot.2018.04.023","volume":"192","author":"X Liu","year":"2019","unstructured":"Liu, X., Song, Y., Guo, Z., Sun, W. & Liu, J. A comprehensive profile and inter-individual variations analysis of the human normal amniotic fluid proteome. J. Proteomics 192, 1\u20139. https:\/\/doi.org\/10.1016\/j.jprot.2018.04.023 (2019).","journal-title":"J. Proteomics"},{"issue":"4","key":"42576_CR21","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1152\/physrev.1995.75.4.749","volume":"75","author":"JA Whitsett","year":"1995","unstructured":"Whitsett, J. A., Nogee, L. M., Weaver, T. E. & Horowitz, A. D. Human surfactant protein B: Structure, function, regulation, and genetic disease. Physiol. Rev. 75(4), 749\u2013757. https:\/\/doi.org\/10.1152\/physrev.1995.75.4.749 (1995).","journal-title":"Physiol. Rev."},{"key":"42576_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020379","author":"S Sciacchitano","year":"2018","unstructured":"Sciacchitano, S. et al. Galectin-3: One molecule for an alphabet of diseases, from A to Z. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms19020379 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"42576_CR23","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1023\/A:1010933404324","volume":"45","author":"L Breiman","year":"2001","unstructured":"Breiman, L. Random forests. Mach. Learn. 45, 5\u201332 (2001).","journal-title":"Mach. Learn."},{"issue":"5","key":"42576_CR24","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/0002-9378(95)90624-x","volume":"173","author":"FR Moya","year":"1995","unstructured":"Moya, F. R. et al. Fetal lung maturation in congenital diaphragmatic hernia. Am. J. Obstet. Gynecol. 173(5), 1401\u20131405. https:\/\/doi.org\/10.1016\/0002-9378(95)90624-x (1995).","journal-title":"Am. J. Obstet. Gynecol."},{"issue":"8","key":"42576_CR25","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/0022-3468(94)90271-2","volume":"29","author":"KM Sullivan","year":"1994","unstructured":"Sullivan, K. M., Hawgood, S., Flake, A. W., Harrison, M. R. & Adzick, N. S. Amniotic fluid phospholipid analysis in the fetus with congenital diaphragmatic hernia. J. Pediatr. Surg. 29(8), 1020\u20131023. https:\/\/doi.org\/10.1016\/0022-3468(94)90271-2 (1994) (discussion 3-4).","journal-title":"J. Pediatr. Surg."},{"issue":"3","key":"42576_CR26","doi-asserted-by":"publisher","first-page":"e586","DOI":"10.1097\/sla.0000000000003943","volume":"275","author":"FM Russo","year":"2022","unstructured":"Russo, F. M. et al. Complementary effect of maternal sildenafil and fetal tracheal occlusion improves lung development in the rabbit model of congenital diaphragmatic Hernia. Ann. Surg. 275(3), e586\u2013e595. https:\/\/doi.org\/10.1097\/sla.0000000000003943 (2022).","journal-title":"Ann. Surg."},{"issue":"7","key":"42576_CR27","doi-asserted-by":"publisher","first-page":"e237","DOI":"10.1371\/journal.pmed.0040237","volume":"4","author":"O Boucherat","year":"2007","unstructured":"Boucherat, O. et al. Surfactant maturation is not delayed in human fetuses with diaphragmatic hernia. PLoS Med. 4(7), e237. https:\/\/doi.org\/10.1371\/journal.pmed.0040237 (2007).","journal-title":"PLoS Med."},{"issue":"2","key":"42576_CR28","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1164\/rccm.2108028","volume":"166","author":"PE Cogo","year":"2002","unstructured":"Cogo, P. E. et al. Surfactant synthesis and kinetics in infants with congenital diaphragmatic hernia. Am. J. Respir. Crit. Care Med. 166(2), 154\u2013158. https:\/\/doi.org\/10.1164\/rccm.2108028 (2002).","journal-title":"Am. J. Respir. Crit. Care Med."},{"issue":"3","key":"42576_CR29","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1183\/09031936.00032212","volume":"41","author":"PE Cogo","year":"2013","unstructured":"Cogo, P. E. et al. Impaired surfactant protein B synthesis in infants with congenital diaphragmatic hernia. Eur. Respir. J. 41(3), 677\u2013682. https:\/\/doi.org\/10.1183\/09031936.00032212 (2013).","journal-title":"Eur. Respir. J."},{"issue":"1","key":"42576_CR30","doi-asserted-by":"publisher","first-page":"L1","DOI":"10.1152\/ajplung.00050.2012","volume":"303","author":"A Anwar","year":"2012","unstructured":"Anwar, A. et al. Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 303(1), L1-l11. https:\/\/doi.org\/10.1152\/ajplung.00050.2012 (2012).","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"issue":"4","key":"42576_CR31","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1152\/japplphysiol.01311.2003","volume":"97","author":"P Li","year":"2004","unstructured":"Li, P., Oparil, S., Feng, W. & Chen, Y. F. Hypoxia-responsive growth factors upregulate periostin and osteopontin expression via distinct signaling pathways in rat pulmonary arterial smooth muscle cells. J. Appl. Physiol. 97(4), 1550\u20131558. https:\/\/doi.org\/10.1152\/japplphysiol.01311.2003 (2004) (discussion 49).","journal-title":"J. Appl. Physiol."},{"issue":"12","key":"42576_CR32","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.2217\/bmm-2021-0009","volume":"15","author":"S Keranov","year":"2021","unstructured":"Keranov, S. et al. Osteopontin and galectin-3 as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension. Biomark. Med. 15(12), 1021\u20131034. https:\/\/doi.org\/10.2217\/bmm-2021-0009 (2021).","journal-title":"Biomark. Med."},{"issue":"9","key":"42576_CR33","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1111\/j.1365-2362.2012.02671.x","volume":"42","author":"M Rosenberg","year":"2012","unstructured":"Rosenberg, M. et al. Osteopontin predicts adverse right ventricular remodelling and dysfunction in pulmonary hypertension. Eur. J. Clin. Invest. 42(9), 933\u2013942. https:\/\/doi.org\/10.1111\/j.1365-2362.2012.02671.x (2012).","journal-title":"Eur. J. Clin. Invest."},{"issue":"1","key":"42576_CR34","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1186\/s12885-021-08495-z","volume":"21","author":"J Huang","year":"2021","unstructured":"Huang, J. et al. Osteopontin isoform c promotes the survival of cisplatin-treated NSCLC cells involving NFATc2-mediated suppression on calcium-induced ROS levels. BMC Cancer 21(1), 750. https:\/\/doi.org\/10.1186\/s12885-021-08495-z (2021).","journal-title":"BMC Cancer"},{"issue":"3","key":"42576_CR35","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1160\/th12-11-0836","volume":"110","author":"J Fischer","year":"2013","unstructured":"Fischer, J. & Meyer-Hoffert, U. Regulation of kallikrein-related peptidases in the skin\u2014From physiology to diseases to therapeutic options. Thromb. Haemost. 110(3), 442\u2013449. https:\/\/doi.org\/10.1160\/th12-11-0836 (2013).","journal-title":"Thromb. Haemost."},{"issue":"6","key":"42576_CR36","doi-asserted-by":"publisher","first-page":"3640","DOI":"10.1074\/jbc.M607567200","volume":"282","author":"CA Borgo\u00f1o","year":"2007","unstructured":"Borgo\u00f1o, C. A. et al. A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J. Biol. Chem. 282(6), 3640\u20133652. https:\/\/doi.org\/10.1074\/jbc.M607567200 (2007).","journal-title":"J. Biol. Chem."},{"key":"42576_CR37","doi-asserted-by":"publisher","DOI":"10.1055\/a-1827-7518","author":"E Jano","year":"2022","unstructured":"Jano, E., Vaz, M. J., Mally, P. N. & Wachtel, E. V. Pilot study investigating brain natriuretic peptide, troponin, galectin-3, and miRNA-126a-5p as biomarkers of persistent pulmonary hypertension in neonates with hypoxic-ischemic injury receiving therapeutic hypothermia. Am. J. Perinatol. https:\/\/doi.org\/10.1055\/a-1827-7518 (2022).","journal-title":"Am. J. Perinatol."},{"issue":"8","key":"42576_CR38","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1007\/s11010-021-04131-3","volume":"476","author":"Q Zhang","year":"2021","unstructured":"Zhang, Q. et al. Activation of AMPK inhibits Galectin-3-induced pulmonary artery smooth muscle cells proliferation by upregulating hippo signaling effector YAP. Mol. Cell Biochem. 476(8), 3037\u20133049. https:\/\/doi.org\/10.1007\/s11010-021-04131-3 (2021).","journal-title":"Mol. Cell Biochem."},{"issue":"6","key":"42576_CR39","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1007\/s00380-015-0691-z","volume":"31","author":"BE Fenster","year":"2016","unstructured":"Fenster, B. E. et al. Galectin-3 levels are associated with right ventricular functional and morphologic changes in pulmonary arterial hypertension. Heart Vessels 31(6), 939\u2013946. https:\/\/doi.org\/10.1007\/s00380-015-0691-z (2016).","journal-title":"Heart Vessels"},{"key":"42576_CR40","doi-asserted-by":"publisher","DOI":"10.1172\/jci157415","author":"O Vorontsov","year":"2022","unstructured":"Vorontsov, O. et al. Amniotic fluid biomarkers predict the severity of congenital cytomegalovirus infection. J. Clin. Invest. https:\/\/doi.org\/10.1172\/jci157415 (2022).","journal-title":"J. Clin. Invest."},{"issue":"8","key":"42576_CR41","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/j.joca.2022.02.622","volume":"30","author":"S Bhutada","year":"2022","unstructured":"Bhutada, S. et al. Forward and reverse degradomics defines the proteolytic landscape of human knee osteoarthritic cartilage and the role of the serine protease HtrA1. Osteoarthr. Cartil. 30(8), 1091\u20131102. https:\/\/doi.org\/10.1016\/j.joca.2022.02.622 (2022).","journal-title":"Osteoarthr. Cartil."},{"key":"42576_CR42","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1214\/aos\/1013699998","volume":"29","author":"Y Benjamini","year":"2001","unstructured":"Benjamini, Y. & Yekutieli, D. The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165\u20131188 (2001).","journal-title":"Ann. Stat."},{"issue":"13","key":"42576_CR43","doi-asserted-by":"publisher","first-page":"3017","DOI":"10.1093\/bioinformatics\/bti448","volume":"21","author":"Y Pawitan","year":"2005","unstructured":"Pawitan, Y., Michiels, S., Koscielny, S., Gusnanto, A. & Ploner, A. False discovery rate, sensitivity and sample size for microarray studies. Bioinformatics 21(13), 3017\u20133024 (2005).","journal-title":"Bioinformatics"},{"key":"42576_CR44","doi-asserted-by":"publisher","DOI":"10.1201\/9781315139470","volume-title":"Classification and Regression Trees","author":"L Breiman","year":"2017","unstructured":"Breiman, L. Classification and Regression Trees (Routledge, New York, 2017)."},{"key":"42576_CR45","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1214\/07-EJS039","volume":"1","author":"H Ishwaran","year":"2007","unstructured":"Ishwaran, H. Variable importance in binary regression trees and forests. Electron. J. Stat. 1, 519\u2013537 (2007).","journal-title":"Electron. J. Stat."},{"key":"42576_CR46","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.patcog.2019.01.036","volume":"90","author":"R O'Brien","year":"2019","unstructured":"O\u2019Brien, R. & Ishwaran, H. A random forests quantile classifier for class imbalanced data. Pattern Recognit. 90, 232\u2013249. https:\/\/doi.org\/10.1016\/j.patcog.2019.01.036 (2019).","journal-title":"Pattern Recognit."},{"key":"42576_CR47","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1214\/aos\/1013203451","volume":"29","author":"JH Friedman","year":"2001","unstructured":"Friedman, J. H. Greedy function approximation: A gradient boosting machine. Ann. Stat. 29, 1189\u20132123 (2001).","journal-title":"Ann. Stat."},{"issue":"D1","key":"42576_CR48","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","volume":"50","author":"Y Perez-Riverol","year":"2022","unstructured":"Perez-Riverol, Y. et al. The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50(D1), D543\u2013D552. https:\/\/doi.org\/10.1093\/nar\/gkab1038 (2022).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-42576-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-42576-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-42576-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:21:48Z","timestamp":1700526108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-42576-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,19]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["42576"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-42576-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,19]]},"assertion":[{"value":"15 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15483"}}