{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:52:29Z","timestamp":1781661149200,"version":"3.54.5"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"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":["BMC Med Genomics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We studied 45 patients with confirmed COVID-19 infection within 10\u00a0days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14\u00a0days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change\u2009\u2265\u20091 versus healthy controls; false-discovery rate\u2009&lt;\u20090.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35\u00a0years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all <jats:italic>p<\/jats:italic>\u2009&gt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-021-01006-w","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T12:02:44Z","timestamp":1623412964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A blood RNA transcriptome signature for COVID-19"],"prefix":"10.1186","volume":"14","author":[{"given":"Philip Kam Weng","family":"Kwan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail B.","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Naftalin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bintou A.","family":"Ahidjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee Keng","family":"Mok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felic","family":"Fanusi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Intan","family":"Permata Sari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siok Ching","family":"Chia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoban Krishna","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan","family":"Alagha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Meng","family":"Tham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Archuleta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"October M.","family":"Sessions","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Hibberd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas I.","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"issue":"10223","key":"1006_CR1","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/S0140-6736(20)30185-9","volume":"395","author":"C Wang","year":"2020","unstructured":"Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The Lancet. 2020;395(10223):470\u20133.","journal-title":"The Lancet"},{"issue":"7309","key":"1006_CR2","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/nature09247","volume":"466","author":"MP Berry","year":"2010","unstructured":"Berry MP, Graham CM, McNab FW, Xu Z, Bloch SA, Oni T, Wilkinson KA, Banchereau R, Skinner J, Wilkinson RJ, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010;466(7309):973\u20137.","journal-title":"Nature"},{"issue":"9","key":"1006_CR3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1055\/a-1217-2397","volume":"70","author":"M Rudrapal","year":"2020","unstructured":"Rudrapal M, Khairnar SJ, Borse LB, Jadhav AG. Coronavirus disease-2019 (COVID-19): an updated review. Drug Res. 2020;70(9):389.","journal-title":"Drug Res"},{"key":"1006_CR4","doi-asserted-by":"crossref","first-page":"175628642093203","DOI":"10.1177\/1756286420932036","volume":"13","author":"G Tsivgoulis","year":"2020","unstructured":"Tsivgoulis G, Palaiodimou L, Katsanos AH, Caso V, K\u00f6hrmann M, Molina C, Cordonnier C, Fischer U, Kelly P, Sharma VK. Neurological manifestations and implications of COVID-19 pandemic. Ther Adv Neurol Disord. 2020;13:1756286420932036.","journal-title":"Ther Adv Neurol Disord"},{"key":"1006_CR5","doi-asserted-by":"crossref","unstructured":"Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to incidence or outcomes of covid-19? 2020, 369:m1548.","DOI":"10.1136\/bmj.m1548"},{"key":"1006_CR6","doi-asserted-by":"crossref","unstructured":"Pan D, Sze S, Minhas JS, Bangash MN, Pareek N, Divall P, Williams CM, Oggioni MR, Squire IB, Nellums LB: The impact of ethnicity on clinical outcomes in COVID-19: a systematic review. EClinicalMedicine 2020:100404.","DOI":"10.1016\/j.eclinm.2020.100404"},{"issue":"1","key":"1006_CR7","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","volume":"9","author":"Y Xiong","year":"2020","unstructured":"Xiong Y, Liu Y, Cao L, Wang D, Guo M, Jiang A, Guo D, Hu W, Yang J, Tang Z. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect. 2020;9(1):761\u201370.","journal-title":"Emerg Microbes Infect"},{"key":"1006_CR8","doi-asserted-by":"crossref","unstructured":"Jafarzadeh A, Jafarzadeh S, Nozari P, Mokhtari P, Nemati M. Lymphopenia an important immunological abnormality in patients with COVID\u201019: possible mechanisms. Scand J Immunol 2020:e12967.","DOI":"10.1111\/sji.12967"},{"key":"1006_CR9","doi-asserted-by":"crossref","unstructured":"Liu J, Li S, Liu J, Liang B, Wang X, Wang H, Li W, Tong Q, Yi J, Zhao L. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMed. 2020:102763.","DOI":"10.1016\/j.ebiom.2020.102763"},{"issue":"9","key":"1006_CR10","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1002\/cbin.11403","volume":"44","author":"N Fathi","year":"2020","unstructured":"Fathi N, Rezaei N. Lymphopenia in COVID-19: therapeutic opportunities. Cell Biol Int. 2020;44(9):1792\u20137.","journal-title":"Cell Biol Int"},{"issue":"1","key":"1006_CR11","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1093\/infdis\/jix519","volume":"217","author":"LAH Do","year":"2018","unstructured":"Do LAH, Pellet J, van Doorn HR, Tran AT, Nguyen BH, Tran TTL, Tran QH, Vo QB, Tran Dac NA, Trinh HN. Host transcription profile in nasal epithelium and whole blood of hospitalized children under 2 years of age with respiratory syncytial virus infection. J Infect Dis. 2018;217(1):134\u201346.","journal-title":"J Infect Dis"},{"issue":"1","key":"1006_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12920-020-0672-7","volume":"13","author":"Y Zerbib","year":"2020","unstructured":"Zerbib Y, Jenkins EK, Shojaei M, Meyers AF, Ho J, Ball TB, Keynan Y, Pisipati A, Kumar A, Kumar A. Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection. BMC Med Genom. 2020;13(1):1\u201313.","journal-title":"BMC Med Genom"},{"issue":"11","key":"1006_CR13","doi-asserted-by":"publisher","first-page":"R127","DOI":"10.1186\/gb-2009-10-11-r127","volume":"10","author":"R Pankla","year":"2009","unstructured":"Pankla R, Buddhisa S, Berry M, Blankenship DM, Bancroft GJ, Banchereau J, Lertmemongkolchai G, Chaussabel D. Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis. Genome Biol. 2009;10(11):R127.","journal-title":"Genome Biol"},{"issue":"1","key":"1006_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12879-020-05116-1","volume":"20","author":"PKW Kwan","year":"2020","unstructured":"Kwan PKW, Periaswamy B, De Sessions PF, Lin W, Molton JS, Naftalin CM, Naim ANM, Hibberd ML, Paton NI. A blood RNA transcript signature for TB exposure in household contacts. BMC Infect Dis. 2020;20(1):1\u20138.","journal-title":"BMC Infect Dis"},{"issue":"1","key":"1006_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-65043-8","volume":"10","author":"A Penn-Nicholson","year":"2020","unstructured":"Penn-Nicholson A, Mbandi SK, Thompson E, Mendelsohn SC, Suliman S, Chegou NN, Malherbe ST, Darboe F, Erasmus M, Hanekom WA. RISK6, a 6-gene transcriptomic signature of TB disease risk, diagnosis and treatment response. Sci Rep. 2020;10(1):1\u201321.","journal-title":"Sci Rep"},{"issue":"1","key":"1006_CR16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15\u201321.","journal-title":"Bioinformatics"},{"issue":"2","key":"1006_CR17","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders S, Pyl PT, Huber W. HTSeq\u2014a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166\u20139.","journal-title":"Bioinformatics"},{"issue":"1","key":"1006_CR18","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139\u201340.","journal-title":"Bioinformatics"},{"key":"1006_CR19","doi-asserted-by":"crossref","unstructured":"Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B (Methodol). 1995;289\u2013300.","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"issue":"D1","key":"1006_CR20","doi-asserted-by":"publisher","first-page":"D447","DOI":"10.1093\/nar\/gku1003","volume":"43","author":"D Szklarczyk","year":"2014","unstructured":"Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP. STRING v10: protein\u2013protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2014;43(D1):D447\u201352.","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"1006_CR21","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1056\/NEJMoa1303657","volume":"370","author":"ST Anderson","year":"2014","unstructured":"Anderson ST, Kaforou M, Brent AJ, Wright VJ, Banwell CM, Chagaluka G, Crampin AC, Dockrell HM, French N, Hamilton MS. Diagnosis of childhood tuberculosis and host RNA expression in Africa. N Engl J Med. 2014;370(18):1712\u201323.","journal-title":"N Engl J Med"},{"issue":"10","key":"1006_CR22","doi-asserted-by":"publisher","first-page":"e1001538","DOI":"10.1371\/journal.pmed.1001538","volume":"10","author":"M Kaforou","year":"2013","unstructured":"Kaforou M, Wright VJ, Oni T, French N, Anderson ST, Bangani N, Banwell CM, Brent AJ, Crampin AC, Dockrell HM. Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med. 2013;10(10):e1001538.","journal-title":"PLoS Med"},{"issue":"1","key":"1006_CR23","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1038\/s41467-018-04579-w","volume":"9","author":"A Singhania","year":"2018","unstructured":"Singhania A, Verma R, Graham CM, Lee J, Tran T, Richardson M, Lecine P, Leissner P, Berry MP, Wilkinson RJ. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nat Commun. 2018;9(1):2308.","journal-title":"Nat Commun"},{"issue":"3","key":"1006_CR24","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.cyto.2008.07.009","volume":"43","author":"S Koyama","year":"2008","unstructured":"Koyama S, Ishii KJ, Coban C, Akira S. Innate immune response to viral infection. Cytokine. 2008;43(3):336\u201341.","journal-title":"Cytokine"},{"issue":"1","key":"1006_CR25","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/v2010298","volume":"2","author":"C Rivas","year":"2010","unstructured":"Rivas C, Aaronson SA, Munoz-Fontela C. Dual role of p53 in innate antiviral immunity. Viruses. 2010;2(1):298\u2013313.","journal-title":"Viruses"},{"issue":"14","key":"1006_CR26","doi-asserted-by":"publisher","first-page":"8802","DOI":"10.1128\/JVI.79.14.8802-8811.2005","volume":"79","author":"E Turpin","year":"2005","unstructured":"Turpin E, Luke K, Jones J, Tumpey T, Konan K, Schultz-Cherry S. Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication. J Virol. 2005;79(14):8802\u201311.","journal-title":"J Virol"},{"issue":"1","key":"1006_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1743-422X-8-285","volume":"8","author":"O Terrier","year":"2011","unstructured":"Terrier O, Josset L, Textoris J, Marcel V, Cartet G, Ferraris O, N\u2019Guyen C, Lina B, Diaz J-J, Bourdon J-C. Cellular transcriptional profiling in human lung epithelial cells infected by different subtypes of influenza A viruses reveals an overall down-regulation of the host p53 pathway. Virol J. 2011;8(1):1\u201311.","journal-title":"Virol J"},{"issue":"1732","key":"1006_CR28","doi-asserted-by":"publisher","first-page":"20160271","DOI":"10.1098\/rstb.2016.0271","volume":"372","author":"C Shannon-Lowe","year":"2017","unstructured":"Shannon-Lowe C, Rickinson AB, Bell AI. Epstein\u2013Barr virus-associated lymphomas. Philos Trans R Soc B Biol Sci. 2017;372(1732):20160271.","journal-title":"Philos Trans R Soc B Biol Sci"},{"issue":"10","key":"1006_CR29","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/S1473-3099(20)30701-5","volume":"20","author":"D Yelin","year":"2020","unstructured":"Yelin D, Wirtheim E, Vetter P, Kalil AC, Bruchfeld J, Runold M, Guaraldi G, Mussini C, Gudiol C, Pujol M. Long-term consequences of COVID-19: research needs. Lancet Infect Dis. 2020;20(10):1115\u20137.","journal-title":"Lancet Infect Dis"},{"key":"1006_CR30","doi-asserted-by":"crossref","unstructured":"Radzikowska U, Ding M, Tan G, Zhakparov D, Peng Y, Wawrzyniak P, Wang M, Li S, Morita H, Altunbulakli C. Distribution of ACE2, CD147, CD26 and other SARS\u2010CoV\u20102 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID\u201019 risk factors. Allergy; 2020.","DOI":"10.1101\/2020.05.14.090332"},{"key":"1006_CR31","doi-asserted-by":"crossref","unstructured":"Gupta R, Misra A. COVID19 in South Asians\/Asian Indians: heterogeneity of data and implications for pathophysiology and research. Diabetes Res Clin Pract; 2020.","DOI":"10.1016\/j.diabres.2020.108267"},{"key":"1006_CR32","unstructured":"White C, Ayoubkhani D. Updating ethnic contrasts in deaths involving the coronavirus (COVID-19), England and Wales: deaths occurring 2 March to 28 July 2020. Office for National Statistics; 2020."},{"key":"1006_CR33","doi-asserted-by":"crossref","unstructured":"Sim BLH, Chidambaram SK, Wong XC, Pathmanathan MD, Peariasamy KM, Hor CP, Chua HJ, Goh PP. Clinical characteristics and risk factors for severe COVID-19 infections in Malaysia: A nationwide observational study. Lancet Reg Health-Western Pac 2020;4:100055.","DOI":"10.1016\/j.lanwpc.2020.100055"},{"issue":"1","key":"1006_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-020-19057-5","volume":"11","author":"J Fajnzylber","year":"2020","unstructured":"Fajnzylber J, Regan J, Coxen K, Corry H, Wong C, Rosenthal A, Worrall D, Giguel F, Piechocka-Trocha A, Atyeo C. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun. 2020;11(1):1\u20139.","journal-title":"Nat Commun"},{"key":"1006_CR35","doi-asserted-by":"crossref","unstructured":"Magleby R, Westblade LF, Trzebucki A, Simon MS, Rajan M, Park J, Goyal P, Safford MM, Satlin MJ. Impact of SARS-CoV-2 viral load on risk of intubation and mortality among hospitalized patients with coronavirus disease 2019. Clin Infect Dis; 2020.","DOI":"10.1093\/cid\/ciaa851"},{"issue":"2","key":"1006_CR36","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3390\/v13020281","volume":"13","author":"M Trunfio","year":"2021","unstructured":"Trunfio M, Venuti F, Alladio F, Longo BM, Burdino E, Cerutti F, Ghisetti V, Bertucci R, Picco C, Bonora S. Diagnostic SARS-CoV-2 cycle threshold value predicts disease severity, survival, and six-month sequelae in COVID-19 symptomatic patients. Viruses. 2021;13(2):281.","journal-title":"Viruses"},{"key":"1006_CR37","doi-asserted-by":"crossref","unstructured":"Rao SN, Manissero D, Steele VR, Pareja J. A narrative systematic review of the clinical utility of cycle threshold values in the context of COVID-19. Infect Dis Ther 2020;1\u201314.","DOI":"10.21203\/rs.3.rs-41867\/v1"},{"issue":"5","key":"1006_CR38","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1513\/AnnalsATS.202008-931RL","volume":"18","author":"IM Zacharioudakis","year":"2021","unstructured":"Zacharioudakis IM, Prasad PJ, Zervou FN, Basu A, Inglima K, Weisenberg SA, Aguero-Rosenfeld ME. Association of SARS-CoV-2 genomic load with outcomes in patients with COVID-19. Ann Am Thorac Soc. 2021;18(5):900.","journal-title":"Ann Am Thorac Soc"},{"key":"1006_CR39","unstructured":"COVID-19 Situation Report. [Ministry of Health, Singapore. https:\/\/covidsitrep.moh.gov.sg. Accessed 14 Dec 2020]."}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-021-01006-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-021-01006-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-021-01006-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T12:03:43Z","timestamp":1623413023000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-021-01006-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1006"],"URL":"https:\/\/doi.org\/10.1186\/s12920-021-01006-w","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,11]]},"assertion":[{"value":"20 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethics approval were approved by the Domain Specific Review Board of the National Healthcare Group, Singapore (NHG-DSRB; DSRB 2020\/00286). All study participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors report no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"155"}}