{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:04:08Z","timestamp":1778850248764,"version":"3.51.4"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T00:00:00Z","timestamp":1594857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH","award":["T32 GM13206"],"award-info":[{"award-number":["T32 GM13206"]}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["17SDG33670339"],"award-info":[{"award-number":["17SDG33670339"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and affects boys in infancy or early childhood. Current methods for diagnosing DMD are often laborious, expensive, invasive, and typically diagnose the disease late in its progression. In an effort to improve the accuracy and ease of diagnosis, this study focused on developing a novel method for diagnosing DMD which combines Raman hyperspectroscopic analysis of blood serum with advanced statistical analysis. Partial least squares discriminant analysis was applied to the spectral dataset acquired from blood serum of a mouse model of Duchenne muscular dystrophy (\n                    <jats:italic>mdx<\/jats:italic>\n                    ) and control mice. Cross-validation showed 95.2% sensitivity and 94.6% specificity for identifying diseased spectra. These results were verified via external validation, which achieved 100% successful classification accuracy at the donor level. This proof-of-concept study presents Raman hyperspectroscopic analysis of blood serum as an easy, fast, non-expensive, and minimally invasive detection method for distinguishing control and\n                    <jats:italic>mdx<\/jats:italic>\n                    model mice, with a strong potential for clinical diagnosis of DMD.\n                  <\/jats:p>","DOI":"10.1038\/s41598-020-68598-8","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T06:02:53Z","timestamp":1594879373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Diagnosis of a model of Duchenne muscular dystrophy in blood serum of mdx mice using Raman hyperspectroscopy"],"prefix":"10.1038","volume":"10","author":[{"given":"Nicole M.","family":"Ralbovsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paromita","family":"Dey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Galfano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bijan K.","family":"Dey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor K.","family":"Lednev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"68598_CR1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1073\/pnas.81.4.1189","volume":"81","author":"G Bulfield","year":"1984","unstructured":"Bulfield, G., Siller, W. G., Wight, P. A. & Moore, K. J. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc. Natl. Acad. Sci. 81, 1189\u20131192 (1984).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"68598_CR2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s10974-015-9406-4","volume":"36","author":"J Manning","year":"2015","unstructured":"Manning, J. & O\u2019Malley, D. What has the mdx mouse model of Duchenne muscular dystrophy contributed to our understanding of this disease?. J. Muscle Res. Cell Motil. 36, 155\u2013167 (2015).","journal-title":"J. Muscle Res. Cell Motil."},{"key":"68598_CR3","unstructured":"Darras, B. T., Urion, D. K. & Ghosh, P. S. in GeneReviews [Internet] (ed Ardinger HH Adam MP, Pagon RA) (University of Washington, Seattle, 2000)."},{"key":"68598_CR4","first-page":"917","volume":"74","author":"HN Oldham","year":"1973","unstructured":"Oldham, H. N., Roe, C. R., Young, W. G. & Dixon, S. H. Intraoperative detection of myocardial damage during coronary artery surgery by plasma creatine phosphokinase isoenzyme analysis. Surgery 74, 917\u2013925 (1973).","journal-title":"Surgery"},{"key":"68598_CR5","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1001\/jama.1978.03280520057019","volume":"239","author":"MA LaPorta","year":"1978","unstructured":"LaPorta, M. A., Linde, H. W., Bruce, D. L. & Fitzsimons, E. J. Elevation of creatine phosphokinase in young men after recreational exercise. J. Am. Med. Assoc. 239, 2685\u20132686 (1978).","journal-title":"J. Am. Med. Assoc."},{"key":"68598_CR6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1001\/archinte.1968.00040010417008","volume":"122","author":"JS Lafair","year":"1968","unstructured":"Lafair, J. S. & Myerson, R. M. Alcoholic myopathy. Arch. Intern. Med. 122, 417\u2013422 (1968).","journal-title":"Arch. Intern. Med."},{"key":"68598_CR7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/bmb\/ldm014","volume":"81\u201382","author":"P Brancaccio","year":"2007","unstructured":"Brancaccio, P., Maffulli, N. & Limongelli, F. M. Creatine kinase monitoring in sport medicine. Br. Med. Bull. 81\u201382, 209\u2013230 (2007).","journal-title":"Br. Med. Bull."},{"key":"68598_CR8","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1001\/jama.1973.03220240032008","volume":"224","author":"MA Nevins","year":"1973","unstructured":"Nevins, M. A., Saran, M., Bright, M. & Lyon, L. J. Pitfalls in interpreting serum creatine phosphokinase activity. JAMA 224, 1382\u20131387 (1973).","journal-title":"JAMA"},{"key":"68598_CR9","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.0954-6820.1966.tb07980.x","volume":"179","author":"A Nygren","year":"1966","unstructured":"Nygren, A. Serum creatine phosphokinase activity in chronic alcoholism, in connection with acute alcohol intoxication. Acta Medica Scand. 179, 623\u2013630 (1966).","journal-title":"Acta Medica Scand."},{"key":"68598_CR10","unstructured":"Shelat, A. M. in A.D.A.M. Medical Encyclopedia (eds David Zieve & Brenda Conaway) (Bethesda, MD, 2018)."},{"key":"68598_CR11","unstructured":"Muscular dystrophy. https:\/\/www.mayoclinic.org\/diseases-conditions\/muscular-dystrophy (2018)."},{"key":"68598_CR12","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.2217\/bmm-2019-0242","volume":"13","author":"K Uaesoontrachoon","year":"2019","unstructured":"Uaesoontrachoon, K. et al. Orthogonal analysis of dystrophin protein and mRNA as a surrogate outcome for drug development. Biomark. Med. 13, 1209\u20131225 (2019).","journal-title":"Biomark. Med."},{"key":"68598_CR13","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.ymthe.2006.04.013","volume":"14","author":"CL Anderson","year":"2006","unstructured":"Anderson, C. L. et al. The mouse dystrophin muscle promoter\/enhancer drives expression of mini-dystrophin in transgenic mdx mice and rescues the dystrophy in these mice. Mol. Ther. 14, 724\u2013734 (2006).","journal-title":"Mol. Ther."},{"key":"68598_CR14","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1365-2990.1991.tb00735.x","volume":"17","author":"T Partridge","year":"1991","unstructured":"Partridge, T. Animal models of muscular dystrophy\u2014What can they teach us?. Neuropathol. Appl. Neurobiol. 17, 353\u2013363 (1991).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"68598_CR15","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1021\/acs.analchem.5b04665","volume":"88","author":"TW Bocklitz","year":"2016","unstructured":"Bocklitz, T. W., Guo, S., Ryabchykov, O., Vogler, N. & Popp, J. R. Raman based molecular imaging and analytics: A magic bullet for biomedical applications!?. Anal. Chem. 88, 133\u2013151 (2016).","journal-title":"Anal. Chem."},{"key":"68598_CR16","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.saa.2019.04.067","volume":"219","author":"NM Ralbovsky","year":"2019","unstructured":"Ralbovsky, N. M. & Lednev, I. K. Raman spectroscopy and chemometrics: A potential universal method for diagnosing cancer. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 219, 463\u2013487 (2019).","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"68598_CR17","first-page":"33","volume":"4","author":"N Ralbovsky","year":"2018","unstructured":"Ralbovsky, N. & Lednev, I. K. Raman hyperspectroscopy shows promise for diagnosis of Alzheimer\u2019s. Biophotonics 4, 33\u201337 (2018).","journal-title":"Biophotonics"},{"key":"68598_CR18","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/jbio.201400060","volume":"8","author":"E Ryzhikova","year":"2015","unstructured":"Ryzhikova, E. et al. Raman spectroscopy of blood serum for Alzheimer\u2019s disease diagnostics: Specificity relative to other types of dementia. J. Biophoton. 8, 584\u2013596 (2015).","journal-title":"J. Biophoton."},{"key":"68598_CR19","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.3233\/JAD-190675","volume":"71","author":"NM Ralbovsky","year":"2019","unstructured":"Ralbovsky, N. M., Halamkova, L., Wall, K., Anderson-Hanley, C. & Lednev, I. K. Screening for Alzheimer\u2019s disease using saliva: a new approach based on machine learning and Raman hyperspectroscopy. J. Alzheimer\u2019s Dis. 71, 1351\u20131359 (2019).","journal-title":"J. Alzheimer's Dis."},{"key":"68598_CR20","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1039\/b602376m","volume":"131","author":"DI Ellis","year":"2006","unstructured":"Ellis, D. I. & Goodacre, R. Metabolic fingerprinting in disease diagnosis: Biomedical applications of infrared and Raman spectroscopy. Analyst 131, 875\u2013885 (2006).","journal-title":"Analyst"},{"key":"68598_CR21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.addr.2015.03.009","volume":"89","author":"K Kong","year":"2015","unstructured":"Kong, K., Kendall, C., Stone, N. & Notingher, I. Raman spectroscopy for medical diagnostics\u2014From in-vitro biofluid assays to in-vivo cancer detection. Adv. Drug Deliv. Rev. 89, 121\u2013134 (2015).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"68598_CR22","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1007\/s00216-012-6117-1","volume":"404","author":"A Zhang","year":"2012","unstructured":"Zhang, A., Sun, H. & Wang, X. Serum metabolomics as a novel diagnostic approach for disease: A systematic review. Anal. Bioanal. Chem. 404, 1239\u20131245 (2012).","journal-title":"Anal. Bioanal. Chem."},{"key":"68598_CR23","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1093\/ndt\/gfs380","volume":"28","author":"J Vanmassenhove","year":"2013","unstructured":"Vanmassenhove, J., Vanholder, R., Nagler, E. & Van Biesen, W. Urinary and serum biomarkers for the diagnosis of acute kidney injury: An in-depth review of the literature. Nephrol. Dial. Transplant. 28, 254\u2013273 (2013).","journal-title":"Nephrol. Dial. Transplant."},{"key":"68598_CR24","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.exphem.2010.10.004","volume":"38","author":"N Sch\u00f6ler","year":"2010","unstructured":"Sch\u00f6ler, N., Langer, C., D\u00f6hner, H., Buske, C. & Kuchenbauer, F. Serum microRNAs as a novel class of biomarkers: a comprehensive review of the literature. Exp. Hematol. 38, 1126\u20131130 (2010).","journal-title":"Exp. Hematol."},{"key":"68598_CR25","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.med.55.091902.105237","volume":"55","author":"KP Rosenblatt","year":"2004","unstructured":"Rosenblatt, K. P. et al. Serum proteomics in cancer diagnosis and management. Annu. Rev. Med. 55, 97\u2013112 (2004).","journal-title":"Annu. Rev. Med."},{"key":"68598_CR26","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.eswa.2005.09.024","volume":"31","author":"C-L Huang","year":"2006","unstructured":"Huang, C.-L. & Wang, C.-J. A GA-based feature selection and parameters optimizationfor support vector machines. Expert Syst. Appl. 31, 231\u2013240 (2006).","journal-title":"Expert Syst. Appl."},{"key":"68598_CR27","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.3390\/app9163256","volume":"9","author":"E Ryzhikova","year":"2019","unstructured":"Ryzhikova, E. et al. Multivariate statistical analysis of surface enhanced Raman spectra of human serum for Alzheimer\u2019s disease diagnosis. Appl. Sci. 9, 3526 (2019).","journal-title":"Appl. Sci."},{"key":"68598_CR28","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.3390\/molecules24234320","volume":"24","author":"B Uribe","year":"2019","unstructured":"Uribe, B. et al. Analysis of the heterogeneous distribution of amiloride and propranolol in dried blood spot by UHPLC-FLD and MALDI-IMS. Molecules 24, 4320 (2019).","journal-title":"Molecules"},{"key":"68598_CR29","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S0895-4356(03)00207-5","volume":"56","author":"SE Bleeker","year":"2003","unstructured":"Bleeker, S. E. et al. External validation is necessary in prediction research: A clinical example. J. Clin. Epidemiol. 56, 826\u2013832 (2003).","journal-title":"J. Clin. Epidemiol."},{"key":"68598_CR30","doi-asserted-by":"crossref","first-page":"4344","DOI":"10.1021\/acs.analchem.7b00106","volume":"89","author":"CK Muro","year":"2017","unstructured":"Muro, C. K. & Lednev, I. K. Race differentiation based on Raman spectroscopy of semen traces for forensic purposes. Anal. Chem. 89, 4344\u20134348 (2017).","journal-title":"Anal. Chem."},{"key":"68598_CR31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/nbm.1419","volume":"23","author":"NK Srivastava","year":"2010","unstructured":"Srivastava, N. K., Pradhan, S., Mittal, B. & Gowda, G. A. N. High resolution NMR based analysis of serum lipids in Duchenne muscular dystrophy patients and its possible diagnostic significance. NMR Biomed. 23, 13\u201322 (2010).","journal-title":"NMR Biomed."},{"key":"68598_CR32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13395-017-0135-9","volume":"7","author":"N Milad","year":"2017","unstructured":"Milad, N. et al. Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy. Skelet. Muscle 7, 19 (2017).","journal-title":"Skelet. Muscle"},{"key":"68598_CR33","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/284470a0","volume":"284","author":"VC Duance","year":"1980","unstructured":"Duance, V. C., Stephens, H. R., Dunn, M., Bailey, A. J. & Dubowitz, V. A role for collagen in the pathogenesis of muscular dystrophy?. Nature 284, 470\u2013472 (1980).","journal-title":"Nature"},{"key":"68598_CR34","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0003-9861(71)90453-X","volume":"144","author":"V Ionasescu","year":"1971","unstructured":"Ionasescu, V., Zellweger, H. & Conway, T. W. Ribosomal protein synthesis in Duchenne muscular dystrophy. Arch. Biochem. Biophys. 144, 51\u201358 (1971).","journal-title":"Arch. Biochem. Biophys."},{"key":"68598_CR35","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1600-0404.1976.tb04800.x","volume":"54","author":"V Ionasescu","year":"1976","unstructured":"Ionasescu, V., Zellweger, H., Ionasescu, R., Lara-Braud, C. & Cancilla, P. A. Protein synthesis in muscle cultures from patients with Duchenne muscular dystrophy: Calcium and A23187 ionophore dependent changes. Acta Neurol. Scand. 54, 241\u2013247 (1976).","journal-title":"Acta Neurol. Scand."},{"key":"68598_CR36","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1600-0404.1977.tb05659.x","volume":"55","author":"V Ionasescu","year":"1977","unstructured":"Ionasescu, V., Lara-Braud, C., Zellweger, H., Ionasescu, R. & Burmeister, L. Fibroblast cultures in Duchenne muscular dystrophy: alterations in synthesis and secretion of collagen and noncollagen proteins. Acta Neurol. Scand. 55, 407\u2013417 (1977).","journal-title":"Acta Neurol. Scand."},{"key":"68598_CR37","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/268241a0","volume":"268","author":"EJ Thompson","year":"1977","unstructured":"Thompson, E. J., Yasin, R., van Beers, G., Nurse, K. & Al-Ani, S. Myogenic defect in human muscular dystrophy. Nature 268, 241\u2013243 (1977).","journal-title":"Nature"},{"key":"68598_CR38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1136\/jmg.2002.002311","volume":"42","author":"AK Lampe","year":"2005","unstructured":"Lampe, A. K. & Bushby, K. M. D. Collagen VI related muscle disorders. J. Med. Genet. 42, 673\u2013685 (2005).","journal-title":"J. Med. Genet."},{"key":"68598_CR39","doi-asserted-by":"crossref","first-page":"6458","DOI":"10.1093\/hmg\/ddu366","volume":"23","author":"Y Hathout","year":"2014","unstructured":"Hathout, Y. et al. Discovery of serum protein biomarkers in the mdx mouse model and cross-species comparison to Duchenne muscular dystrophy patients. Hum. Mol. Genet. 23, 6458\u20136469 (2014).","journal-title":"Hum. Mol. Genet."},{"key":"68598_CR40","doi-asserted-by":"crossref","first-page":"7153","DOI":"10.1073\/pnas.1507719112","volume":"112","author":"Y Hathout","year":"2015","unstructured":"Hathout, Y. et al. Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. 112, 7153\u20137158 (2015).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"68598_CR41","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1002\/pmic.200700857","volume":"8","author":"S Alagaratnam","year":"2008","unstructured":"Alagaratnam, S. et al. Serum protein profiling in mice: identification of Factor XIIIa as a potential biomarker for muscular dystrophy. Proteomics 8, 1552\u20131563 (2008).","journal-title":"Proteomics"},{"key":"68598_CR42","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/prca.201300072","volume":"8","author":"FC Martin","year":"2014","unstructured":"Martin, F. C. et al. Fibronectin is a serum biomarker for Duchenne muscular dystrophy. Proteom. Clin. Appl. 8, 269\u2013278 (2014).","journal-title":"Proteom. Clin. Appl."},{"key":"68598_CR43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12014-016-9109-x","volume":"13","author":"Y Hathout","year":"2016","unstructured":"Hathout, Y. et al. Clinical utility of serum biomarkers in Duchenne muscular dystrophy. Clin. Proteom. 13, 9 (2016).","journal-title":"Clin. Proteom."},{"key":"68598_CR44","doi-asserted-by":"crossref","first-page":"e91514","DOI":"10.1371\/journal.pone.0091514","volume":"9","author":"DI Stapleton","year":"2014","unstructured":"Stapleton, D. I. et al. Dysfunctional muscle and liver glycogen metabolism in mdx dystrophic mice. PLoS ONE 9, e91514 (2014).","journal-title":"PLoS ONE"},{"key":"68598_CR45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41536-018-0045-4","volume":"3","author":"N Yucel","year":"2018","unstructured":"Yucel, N., Chang, A. C., Day, J. W., Rosenthal, N. & Blau, H. M. Humanizing the mdx mouse model of DMD: The long and the short of it. NPJ Regen. Med. 3, 1\u201311 (2018).","journal-title":"NPJ Regen. Med."},{"key":"68598_CR46","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1101\/gad.198085.112","volume":"26","author":"BK Dey","year":"2012","unstructured":"Dey, B. K., Gagan, J., Yan, Z. & Dutta, A. miR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes Dev. 26, 2180\u20132191 (2012).","journal-title":"Genes Dev."},{"key":"68598_CR47","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1101\/gad.234419.113","volume":"28","author":"BK Dey","year":"2014","unstructured":"Dey, B. K., Pfeifer, K. & Dutta, A. The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev. 28, 491\u2013501 (2014).","journal-title":"Genes Dev."},{"key":"68598_CR48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3748\/wjg.v20.i1.163","volume":"20","author":"T Dawiskiba","year":"2014","unstructured":"Dawiskiba, T. et al. Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases. World J. Gastroenterol. 20, 163\u2013174 (2014).","journal-title":"World J. Gastroenterol."},{"key":"68598_CR49","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/nm1202-802","volume":"8","author":"JT Brindle","year":"2002","unstructured":"Brindle, J. T. et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics. Nat. Med. 8, 1439\u20131445 (2002).","journal-title":"Nat. Med."},{"key":"68598_CR50","doi-asserted-by":"crossref","unstructured":"Liu, W., Sun, Z., Chen, J. & Jing, C. Raman spectroscopy in colorectal cancer diagnostics: Comparison of PCA-LDA and PLS-DA models. J. Spectrosc (2016).","DOI":"10.1155\/2016\/1603609"},{"key":"68598_CR51","doi-asserted-by":"crossref","first-page":"20266","DOI":"10.18632\/oncotarget.14865","volume":"8","author":"PT Winnard Jr","year":"2017","unstructured":"Winnard, P. T. Jr. et al. Organ-specific isogenic metastatic breast cancer cell lines exhibit distinct Raman spectral signatures and metabolomes. Oncotarget 8, 20266\u201320287 (2017).","journal-title":"Oncotarget"},{"key":"68598_CR52","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/0003702817746947","volume":"72","author":"V Olmos","year":"2018","unstructured":"Olmos, V., Bedia, C., Tauler, R. & Juan, A. D. Preprocessing tools applied to improve the assessment of aldrin effects on prostate cancer cells using Raman spectroscopy. Appl. Spectrosc. 72, 489\u2013500 (2018).","journal-title":"Appl. Spectrosc."},{"key":"68598_CR53","doi-asserted-by":"crossref","first-page":"8542","DOI":"10.1039\/C6AY02559E","volume":"8","author":"B Brozek-Pluska","year":"2016","unstructured":"Brozek-Pluska, B., Kope\u0107, M. & Abramczyk, H. Development of a new diagnostic Raman method for monitoring epigenetic modifications in the cancer cells of human breast tissue. Anal. Methods 8, 8542\u20138553 (2016).","journal-title":"Anal. Methods"},{"key":"68598_CR54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.saa.2017.06.037","volume":"188","author":"H Abramczyk","year":"2018","unstructured":"Abramczyk, H. & Imiela, A. The biochemical, nanomechanical and chemometric signatures of brain cancer. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 188, 8\u201319 (2018).","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"68598_CR55","unstructured":"Bergholt, M. S. et al. in Biomedical Vibrational Spectroscopy VI: Advances in Research and Industry. 89390M (International Society for Optics and Photonics)."},{"key":"68598_CR56","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/jbio.201400141","volume":"9","author":"MS Bergholt","year":"2016","unstructured":"Bergholt, M. S. et al. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy enhances real-time in vivo diagnosis of adenomatous polyps during colonoscopy. J. Biophoton. 9, 333\u2013342. https:\/\/doi.org\/10.1002\/jbio.201400141 (2016).","journal-title":"J. Biophoton."},{"key":"68598_CR57","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1021\/ac503287u","volume":"87","author":"MS Bergholt","year":"2015","unstructured":"Bergholt, M. S. et al. Characterizing variability of in vivo Raman spectroscopic properties of different anatomical sites of normal colorectal tissue towards cancer diagnosis at colonoscopy. Anal. Chem. 87, 960\u2013966 (2015).","journal-title":"Anal. Chem."},{"key":"68598_CR58","doi-asserted-by":"crossref","first-page":"12957","DOI":"10.1038\/srep12957","volume":"5","author":"J Wang","year":"2015","unstructured":"Wang, J. et al. Simultaneous fingerprint and high-wavenumber fiber-optic Raman spectroscopy improves in vivo diagnosis of esophageal squamous cell carcinoma at endoscopy. Sci. Rep. 5, 12957 (2015).","journal-title":"Sci. Rep."},{"key":"68598_CR59","doi-asserted-by":"publisher","first-page":"3705","DOI":"10.1364\/boe.7.003705","volume":"7","author":"K Lin","year":"2016","unstructured":"Lin, K., Zheng, W., Lim, C. M. & Huang, Z. Real-time in vivo diagnosis of laryngeal carcinoma with rapid fiber-optic Raman spectroscopy. Biomed. Opt Express 7, 3705\u20133715. https:\/\/doi.org\/10.1364\/boe.7.003705 (2016).","journal-title":"Biomed. Opt Express"},{"key":"68598_CR60","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/exd.12768","volume":"24","author":"J Schleusener","year":"2015","unstructured":"Schleusener, J. et al. In vivo study for the discrimination of cancerous and normal skin using fibre probe-based Raman spectroscopy. Exp. Dermatol. 24, 767\u2013772 (2015).","journal-title":"Exp. Dermatol."},{"key":"68598_CR61","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1039\/C5FD00151J","volume":"187","author":"J Wang","year":"2016","unstructured":"Wang, J. et al. Fiber-optic Raman spectroscopy for in vivo diagnosis of gastric dysplasia. Faraday Discuss. 187, 377\u2013392 (2016).","journal-title":"Faraday Discuss."},{"key":"68598_CR62","doi-asserted-by":"crossref","first-page":"8303","DOI":"10.1007\/s00216-015-8727-x","volume":"407","author":"J Wang","year":"2015","unstructured":"Wang, J. et al. Comparative study of the endoscope-based bevelled and volume fiber-optic Raman probes for optical diagnosis of gastric dysplasia in vivo at endoscopy. Anal. Bioanal. Chem. 407, 8303\u20138310 (2015).","journal-title":"Anal. Bioanal. Chem."},{"key":"68598_CR63","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/cem.785","volume":"17","author":"M Barker","year":"2003","unstructured":"Barker, M. & Rayens, W. Partial least squares for discrimination. J. Chemom. 17, 166\u2013173 (2003).","journal-title":"J. Chemom."},{"key":"68598_CR64","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/BF00175354","volume":"4","author":"D Whitley","year":"1994","unstructured":"Whitley, D. A genetic algorithm tutorial. Stat Comput 4, 65\u201385 (1994).","journal-title":"Stat Comput"},{"key":"68598_CR65","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1016\/j.saa.2004.11.017","volume":"61","author":"C Krafft","year":"2005","unstructured":"Krafft, C., Neudert, L., Simat, T. & Salzer, R. Near infrared Raman spectra of human brain lipids. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 61, 1529\u20131535 (2005).","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"68598_CR66","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1039\/b304992b","volume":"126","author":"N Stone","year":"2004","unstructured":"Stone, N., Kendall, C., Smith, J., Crow, P. & Barr, H. Raman spectroscopy for identification of epithelial cancers. Faraday Discuss. 126, 141\u2013157 (2004).","journal-title":"Faraday Discuss."},{"key":"68598_CR67","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1080\/05704928.2014.923902","volume":"50","author":"ACS Talari","year":"2014","unstructured":"Talari, A. C. S., Movasaghi, Z., Rehman, S. & Rehman, I. U. Raman spectroscopy of biological tissues. Appl. Spectrosc. Rev. 50, 46\u2013111 (2014).","journal-title":"Appl. Spectrosc. Rev."},{"key":"68598_CR68","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/sj.bjc.6603102","volume":"94","author":"G Shetty","year":"2006","unstructured":"Shetty, G., Kendall, C., Shepherd, N., Stone, N. & Barr, H. Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus. Br. J. Cancer 94, 1460\u20131464 (2006).","journal-title":"Br. J. Cancer"},{"key":"68598_CR69","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/jemt.20229","volume":"68","author":"W-T Cheng","year":"2005","unstructured":"Cheng, W.-T., Liu, M.-T., Liu, H.-N. & Lin, S.-Y. Micro-Raman spectroscopy used to identify and grade human skin pilomatrixoma. Microsc. Res. Tech. 68, 75\u201379 (2005).","journal-title":"Microsc. Res. Tech."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-68598-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-68598-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-68598-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T08:24:57Z","timestamp":1670315097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-68598-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,16]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["68598"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-68598-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.01.08.897793","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,16]]},"assertion":[{"value":"31 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","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":"11734"}}