{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:41:49Z","timestamp":1779288109540,"version":"3.51.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatitis B virus (HBV) infection is a critical global health issue and moderately epidemic in Western China, but HBV molecular epidemiology characteristics are still limited. We conducted this study to investigate HBV genotypes and antiviral resistant mutations in this multi-ethnic area. A total of 1316 HBV patients were recruited from four ethnic groups from 2011 to 2013. Genotypes and resistant mutations were determined by Sanger sequencing. Four genotypes (B, C, D and C\/D) were identified. Genotype B and C were common in Han population, while genotype D was predominant in Uygurs. Genotype C was the major genotype in both Tibetans and Yis and recombinant C\/D was found in Tibetans only. Lamivudine resistance was common in all populations, especially in Hans with prevalence of 42.8%. Entecavir resistance was barely observed regardless of ethnicity. Genotype C isolates had higher rates of rtA181T\/V than genotype B (13.5% vs. 5.1%, P\u2009&lt;\u20090.001), in accordance with higher prevalence of resistance to adefovir (20.0% vs. 9.5%, P\u2009&lt;\u20090.001). While incidence of resistant mutations to other drugs and clinical factors showed no difference among different genotypes. HBV genotypes and resistance-conferring mutations had different geographic and demographic distributions in Western China, which provided molecular epidemiology data for clinical management.<\/jats:p>","DOI":"10.1038\/srep17413","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T11:10:36Z","timestamp":1448622636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China"],"prefix":"10.1038","volume":"5","author":[{"given":"Qi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binwu","family":"Ying","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanmin","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanlan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,11,27]]},"reference":[{"key":"BFsrep17413_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0140-6736(14)61682-2","volume":"385","author":"GBD Mortality","year":"2015","unstructured":"Mortality, G. B. D. & Causes of Death, C. Global, regional and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117\u2013171 (2015).","journal-title":"Lancet"},{"key":"BFsrep17413_CR2","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1016\/S0140-6736(14)60220-8","volume":"384","author":"C Trepo","year":"2014","unstructured":"Trepo, C., Chan, H. L. & Lok, A. Hepatitis B virus infection. Lancet 384, 2053\u20132063 (2014).","journal-title":"Lancet"},{"key":"BFsrep17413_CR3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/S0928-4346(96)82012-3","volume":"5","author":"G-L Xia","year":"1996","unstructured":"Xia, G.-L. et al. Prevalence of hepatitis B and C virus infections in the general Chinese population. Results from a nationwide cross-sectional seroepidemiologic study of hepatitis A, B, C, D and E virus infections in China, 1992. Int Hepatol Commun 5, 62\u201373 (1996).","journal-title":"Int Hepatol Commun"},{"key":"BFsrep17413_CR4","doi-asserted-by":"publisher","first-page":"6550","DOI":"10.1016\/j.vaccine.2009.08.048","volume":"27","author":"X Liang","year":"2009","unstructured":"Liang, X. et al. Epidemiological serosurvey of hepatitis B in China--declining HBV prevalence due to hepatitis B vaccination. Vaccine 27, 6550\u20136557 (2009).","journal-title":"Vaccine"},{"key":"BFsrep17413_CR5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1872-034X.2009.00601.x","volume":"40","author":"F Kurbanov","year":"2010","unstructured":"Kurbanov, F., Tanaka, Y. & Mizokami, M. Geographical and genetic diversity of the human hepatitis B virus. Hepatol Res 40, 14\u201330 (2010).","journal-title":"Hepatol Res"},{"key":"BFsrep17413_CR6","doi-asserted-by":"publisher","first-page":"5657","DOI":"10.1128\/JVI.02010-07","volume":"82","author":"TT Tran","year":"2008","unstructured":"Tran, T. T., Trinh, T. N. & Abe, K. New complex recombinant genotype of hepatitis B virus identified in Vietnam. J Virol 82, 5657\u20135663 (2008).","journal-title":"J Virol"},{"key":"BFsrep17413_CR7","doi-asserted-by":"publisher","first-page":"10538","DOI":"10.1128\/JVI.00462-09","volume":"83","author":"K Tatematsu","year":"2009","unstructured":"Tatematsu, K. et al. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol 83, 10538\u201310547 (2009).","journal-title":"J Virol"},{"key":"BFsrep17413_CR8","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1111\/j.1440-1746.2010.06541.x","volume":"26","author":"CL Lin","year":"2011","unstructured":"Lin, C. L. & Kao, J. H. The clinical implications of hepatitis B virus genotype: Recent advances. J Gastroenterol Hepatol 26 Suppl 1, 123\u2013130 (2011).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep17413_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1055\/s-0033-1345716","volume":"33","author":"CJ Liu","year":"2013","unstructured":"Liu, C. J. & Kao, J. H. Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J. Semin Liver Dis 33, 97\u2013102 (2013).","journal-title":"Semin Liver Dis"},{"key":"BFsrep17413_CR10","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.3201\/eid1411.080437","volume":"14","author":"CM Olinger","year":"2008","unstructured":"Olinger, C. M. et al. Possible new hepatitis B virus genotype, southeast Asia. Emerg Infect Dis 14, 1777\u20131780 (2008).","journal-title":"Emerg Infect Dis"},{"key":"BFsrep17413_CR11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/jgh.12220","volume":"28","author":"Y Cui","year":"2013","unstructured":"Cui, Y. & Jia, J. Update on epidemiology of hepatitis B and C in China. J Gastroenterol Hepatol 28 Suppl 1, 7\u201310 (2013).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep17413_CR12","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.1365-2893.2005.00657.x","volume":"12","author":"G Zeng","year":"2005","unstructured":"Zeng, G. et al. Geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. J Viral Hepat 12, 609\u2013617 (2005).","journal-title":"J Viral Hepat"},{"key":"BFsrep17413_CR13","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1099\/0022-1317-83-11-2773","volume":"83","author":"C Cui","year":"2002","unstructured":"Cui, C. et al. The dominant hepatitis B virus genotype identified in Tibet is a C\/D hybrid. J Gen Virol 83, 2773\u20132777 (2002).","journal-title":"J Gen Virol"},{"key":"BFsrep17413_CR14","doi-asserted-by":"publisher","first-page":"e18708","DOI":"10.1371\/journal.pone.0018708","volume":"6","author":"B Zhou","year":"2011","unstructured":"Zhou, B. et al. Geographical and ethnic distribution of the HBV C\/D recombinant on the Qinghai-Tibet Plateau. PLoS One 6, e18708 (2011).","journal-title":"PLoS One"},{"key":"BFsrep17413_CR15","doi-asserted-by":"publisher","first-page":"1675","DOI":"10.1002\/jmv.24002","volume":"86","author":"B Wang","year":"2014","unstructured":"Wang, B. et al. Distribution and diversity of hepatitis B virus genotypes in Yunnan, China. J Med Virol 86, 1675\u20131682 (2014).","journal-title":"J Med Virol"},{"key":"BFsrep17413_CR16","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1158\/1055-9965.EPI-09-1001","volume":"19","author":"J Yin","year":"2010","unstructured":"Yin, J. et al. Distribution and hepatocellular carcinoma-related viral properties of hepatitis B virus genotypes in Mainland China: a community-based study. Cancer Epidemiol Biomarkers Prev 19, 777\u2013786 (2010).","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"BFsrep17413_CR17","first-page":"1425","volume":"36","author":"CT Wai","year":"2002","unstructured":"Wai, C. T., Chu, C. J., Hussain, M. & Lok, A. S. HBV genotype B is associated with better response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C. Hepatology 36, 1425\u20131430 (2002).","journal-title":"Hepatology"},{"key":"BFsrep17413_CR18","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1136\/gut.2004.060327","volume":"54","author":"A Erhardt","year":"2005","unstructured":"Erhardt, A. et al. Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut 54, 1009\u20131013 (2005).","journal-title":"Gut"},{"key":"BFsrep17413_CR19","doi-asserted-by":"publisher","first-page":"e2161","DOI":"10.1053\/j.gastro.2009.03.006","volume":"136","author":"P Marcellin","year":"2009","unstructured":"Marcellin, P. et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology 136, 2169-2179 e2161\u20132164 (2009).","journal-title":"Gastroenterology"},{"key":"BFsrep17413_CR20","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1053\/j.gastro.2012.01.044","volume":"142","author":"SJ Scaglione","year":"2012","unstructured":"Scaglione, S. J. & Lok, A. S. Effectiveness of hepatitis B treatment in clinical practice. Gastroenterology 142, 1360\u20131368 e1361 (2012).","journal-title":"Gastroenterology"},{"key":"BFsrep17413_CR21","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cgh.2013.04.036","volume":"12","author":"S Yapali","year":"2014","unstructured":"Yapali, S., Talaat, N. & Lok, A. S. Management of hepatitis B: our practice and how it relates to the guidelines. Clin Gastroenterol Hepatol 12, 16\u201326 (2014).","journal-title":"Clin Gastroenterol Hepatol"},{"key":"BFsrep17413_CR22","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/S0140-6736(09)60207-5","volume":"373","author":"YF Liaw","year":"2009","unstructured":"Liaw, Y. F. & Chu, C. M. Hepatitis B virus infection. Lancet 373, 582\u2013592 (2009).","journal-title":"Lancet"},{"key":"BFsrep17413_CR23","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1086\/368083","volume":"36","author":"CL Lai","year":"2003","unstructured":"Lai, C. L. et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis 36, 687\u2013696 (2003).","journal-title":"Clin Infect Dis"},{"key":"BFsrep17413_CR24","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1053\/j.gastro.2009.08.063","volume":"137","author":"F Zoulim","year":"2009","unstructured":"Zoulim, F. & Locarnini, S. Hepatitis B Virus Resistance to Nucleos(t)ide Analogues. Gastroenterology 137, 1593\u20131608.e1592 (2009).","journal-title":"Gastroenterology"},{"key":"BFsrep17413_CR25","doi-asserted-by":"publisher","first-page":"4363","DOI":"10.1128\/JCM.01518-10","volume":"48","author":"X Li","year":"2010","unstructured":"Li, X. et al. Hepatitis B virus (HBV) subgenotypes C2 and B2 differ in lamivudine- and adefovir-resistance-associated mutational patterns in HBV-infected Chinese patients. J Clin Microbiol 48, 4363\u20134369 (2010).","journal-title":"J Clin Microbiol"},{"key":"BFsrep17413_CR26","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1111\/j.1365-2893.2010.01360.x","volume":"18","author":"Y Liu","year":"2011","unstructured":"Liu, Y. et al. Genotypic resistance profile of hepatitis B virus (HBV) in a large cohort of nucleos(t)ide analogue-experienced Chinese patients with chronic HBV infection. J Viral Hepat 18, e29\u201339 (2011).","journal-title":"J Viral Hepat"},{"key":"BFsrep17413_CR27","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S0168-8278(01)00283-5","volume":"36","author":"M Buti","year":"2002","unstructured":"Buti, M. et al. Is hepatitis B virus subtype testing useful in predicting virological response and resistance to lamivudine? J Hepatol 36, 445\u2013446 (2002).","journal-title":"J Hepatol"},{"key":"BFsrep17413_CR28","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1002\/hep.22075","volume":"47","author":"J Hou","year":"2008","unstructured":"Hou, J. et al. Telbivudine versus lamivudine in Chinese patients with chronic hepatitis B: Results at 1 year of a randomized, double-blind trial. Hepatology 47, 447\u2013454 (2008).","journal-title":"Hepatology"},{"key":"BFsrep17413_CR29","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0168-8278(02)00410-5","volume":"38","author":"N Akuta","year":"2003","unstructured":"Akuta, N. et al. The influence of hepatitis B virus genotype on the development of lamivudine resistance during long-term treatment. J Hepatol 38, 315\u2013321 (2003).","journal-title":"J Hepatol"},{"key":"BFsrep17413_CR30","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1111\/j.1440-1746.2006.04630.x","volume":"22","author":"AJ Thompson","year":"2007","unstructured":"Thompson, A. J. et al. Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors. J Gastroenterol Hepatol 22, 1078\u20131085 (2007).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep17413_CR31","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/jgh.12831","volume":"30","author":"Q Zhang","year":"2015","unstructured":"Zhang, Q. et al. Incidence of natural resistance mutations in naive chronic hepatitis B patients: a systematic review and meta-analysis. J Gastroenterol Hepatol 30, 252\u2013261 (2015).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep17413_CR32","doi-asserted-by":"publisher","first-page":"S36","DOI":"10.1111\/j.1872-034X.2007.00102.x","volume":"37","author":"Z Wang","year":"2007","unstructured":"Wang, Z., Huang, Y., Wen, S., Zhou, B. & Hou, J. Hepatitis B virus genotypes and subgenotypes in China. Hepatol Res 37, S36\u201341 (2007).","journal-title":"Hepatol Res"},{"key":"BFsrep17413_CR33","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1002\/jmv.23965","volume":"86","author":"L Shen","year":"2014","unstructured":"Shen, L. et al. Molecular epidemiological study of hepatitis B virus genotypes in Southwest, China. J Med Virol 86, 1307\u20131313 (2014).","journal-title":"J Med Virol"},{"key":"BFsrep17413_CR34","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1002\/jmv.21902","volume":"82","author":"H Damerow","year":"2010","unstructured":"Damerow, H. et al. Mutation pattern of lamivudine resistance in relation to hepatitis B genotypes: hepatitis B genotypes differ in their lamivudine resistance associated mutation pattern. J Med Virol 82, 1850\u20131858 (2010).","journal-title":"J Med Virol"},{"key":"BFsrep17413_CR35","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1177\/135965350300800610","volume":"8","author":"MF Yuen","year":"2003","unstructured":"Yuen, M. F. et al. Hepatitis B virus genotypes B and C do not affect the antiviral response to lamivudine. Antivir Ther 8, 531\u2013534 (2003).","journal-title":"Antivir Ther"},{"key":"BFsrep17413_CR36","doi-asserted-by":"publisher","first-page":"1066A","DOI":"10.1016\/j.jhep.2010.11.032","volume":"54","author":"L Yuen","year":"2011","unstructured":"Yuen, L., Littlejohn, M., Ayres, A., Edwards, R. & Locarnini, S. A. Different patterns of primary antiviral drug resistance pathways in relation to hepatitis B virus genotypes: Preferential selection of RTA181T+\/\u2212 RTN236T in asian versus european patients. Hepatology 54, 1066A\u20131067A (2011).","journal-title":"Hepatology"},{"key":"BFsrep17413_CR37","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1056\/NEJMoa051287","volume":"354","author":"CL Lai","year":"2006","unstructured":"Lai, C. L. et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 354, 1011\u20131020 (2006).","journal-title":"N Engl J Med"},{"key":"BFsrep17413_CR38","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.1002\/hep.22841","volume":"49","author":"DJ Tenney","year":"2009","unstructured":"Tenney, D. J. et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naive patients is rare through 5 years of therapy. Hepatology 49, 1503\u20131514 (2009).","journal-title":"Hepatology"},{"key":"BFsrep17413_CR39","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.1053\/j.gastro.2006.04.007","volume":"130","author":"M Sherman","year":"2006","unstructured":"Sherman, M. et al. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology 130, 2039\u20132049 (2006).","journal-title":"Gastroenterology"},{"key":"BFsrep17413_CR40","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1002\/hep.22323","volume":"48","author":"M Sherman","year":"2008","unstructured":"Sherman, M. et al. Entecavir therapy for lamivudine-refractory chronic hepatitis B: improved virologic, biochemical and serology outcomes through 96 weeks. Hepatology 48, 99\u2013108 (2008).","journal-title":"Hepatology"},{"key":"BFsrep17413_CR41","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1002\/jmv.23895","volume":"86","author":"J Yang","year":"2014","unstructured":"Yang, J., Chen, X., Zhang, H. & Chen, G. HBV genotype C strains with spontaneous YMDD mutations may be a risk factor for hepatocellular carcinoma. J Med Virol 86, 913\u2013917 (2014).","journal-title":"J Med Virol"},{"key":"BFsrep17413_CR42","doi-asserted-by":"publisher","first-page":"141","DOI":"10.3851\/IMP2813","volume":"20","author":"X Li","year":"2015","unstructured":"Li, X. et al. Investigation into drug-resistant mutations of HBV from 845 nucleoside\/nucleotide analogue-naive Chinese patients with chronic HBV infection. Antivir Ther 20, 141\u2013147 (2015).","journal-title":"Antivir Ther"},{"key":"BFsrep17413_CR43","doi-asserted-by":"publisher","first-page":"e0117429","DOI":"10.1371\/journal.pone.0117429","volume":"10","author":"J Xu","year":"2015","unstructured":"Xu, J. et al. Pre-existing mutations in reverse transcriptase of hepatitis B virus in treatment-naive Chinese patients with chronic hepatitis B. PLoS One 10, e0117429 (2015).","journal-title":"PLoS One"},{"key":"BFsrep17413_CR44","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1086\/597808","volume":"199","author":"S Margeridon-Thermet","year":"2009","unstructured":"Margeridon-Thermet, S. et al. Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients. J Infect Dis 199, 1275\u20131285 (2009).","journal-title":"J Infect Dis"}],"updated-by":[{"DOI":"10.1038\/srep20451","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T00:00:00Z","timestamp":1454025600000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep17413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep17413","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep17413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T19:31:30Z","timestamp":1672947090000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep17413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,27]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2015,12,22]]}},"alternative-id":["BFsrep17413"],"URL":"https:\/\/doi.org\/10.1038\/srep17413","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,27]]},"assertion":[{"value":"29 July 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2016","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17413"}}