{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:38:25Z","timestamp":1772170705382,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,25]],"date-time":"2023-02-25T00:00:00Z","timestamp":1677283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["MOST109-2113-M-006-015"],"award-info":[{"award-number":["MOST109-2113-M-006-015"]}]},{"name":"National Science and Technology Council, Taiwan","award":["MOST110-2113-M-006-014"],"award-info":[{"award-number":["MOST110-2113-M-006-014"]}]},{"name":"National Science and Technology Council, Taiwan","award":["MOST111-2113-M-006-011"],"award-info":[{"award-number":["MOST111-2113-M-006-011"]}]},{"name":"National Science and Technology Council, Taiwan","award":["R111-02"],"award-info":[{"award-number":["R111-02"]}]},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan","award":["MOST109-2113-M-006-015"],"award-info":[{"award-number":["MOST109-2113-M-006-015"]}]},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan","award":["MOST110-2113-M-006-014"],"award-info":[{"award-number":["MOST110-2113-M-006-014"]}]},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan","award":["MOST111-2113-M-006-011"],"award-info":[{"award-number":["MOST111-2113-M-006-011"]}]},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan","award":["R111-02"],"award-info":[{"award-number":["R111-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hair may be a potential biospecimen to discover biomarkers for Alzheimer\u2019s disease (AD) since it reflects the integral metabolic profiles of body burden over several months. Here, we described the AD biomarker discovery in the hair using a high-resolution mass spectrometry (HRMS)-based untargeted metabolomics approach. A total of 24 patients with AD and 24 age- and sex-matched cognitively healthy controls were recruited. The hair samples were collected 0.1-cm away from the scalp and further cut into 3-cm segments. Hair metabolites were extracted by ultrasonication with methanol\/phosphate-buffered saline 50\/50 (v\/v) for 4 h. A total of 25 discriminatory chemicals in hair between the patients with AD and controls were discovered and identified. The AUC value achieved 0.85 (95% CI: 0.72~0.97) in patients with very mild AD compared to healthy controls using a composite panel of the 9 biomarker candidates, indicating high potential for the initiation or promotion phase of AD dementia in the early stage. A metabolic panel combined with the nine metabolites may be used as biomarkers for the early detection of AD. The hair metabolome can be used to reveal metabolic perturbations for biomarker discovery. Investigating perturbations of the metabolites will offer insight into the pathogenesis of AD.<\/jats:p>","DOI":"10.3390\/molecules28052166","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:10:46Z","timestamp":1677463846000},"page":"2166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovering Hair Biomarkers of Alzheimer\u2019s Disease Using High Resolution Mass Spectrometry-Based Untargeted Metabolomics"],"prefix":"10.3390","volume":"28","author":[{"given":"Yu-Hsiang","family":"Su","sequence":"first","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Wei","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jen-Yi","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-7583","authenticated-orcid":false,"given":"Pi-Shan","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru-Hsueh","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0504-2053","authenticated-orcid":false,"given":"Chih-Hsing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao-Chi","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan"},{"name":"Department of Food Safety\/Hygiene and Risk Management, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,25]]},"reference":[{"key":"ref_1","first-page":"371","article-title":"Diagnosis of Early Alzheimer\u2019s Disease: Clinical Practice in 2021","volume":"8","author":"Porsteinsson","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3233\/JAD-160907","article-title":"Recent Progress in Alzheimer\u2019s Disease Research, Part 3: Diagnosis and Treatment","volume":"57","author":"Hane","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_3","first-page":"e12064","article-title":"Untargeted metabolomics reveal dysregulations in sugar, methionine, and tyrosine pathways in the prodromal state of AD","volume":"12","author":"Hajjar","year":"2020","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/brain\/awm336","article-title":"11C PiB and structural MRI provide complementary information in imaging of Alzheimer\u2019s disease and amnestic mild cognitive impairment","volume":"131","author":"Jack","year":"2008","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/ageing\/afy004","article-title":"The role of biomarkers and imaging in the clinical diagnosis of dementia","volume":"47","author":"Bayer","year":"2018","journal-title":"Age Ageing"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2174\/1567205018666211022164952","article-title":"Cerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer\u2019s Disease","volume":"18","author":"Wattmo","year":"2021","journal-title":"Curr. Alzheimer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fbioe.2015.00023","article-title":"Analytical methods in untargeted metabolomics: State of the art in 2015","volume":"3","author":"Alonso","year":"2015","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"D608","DOI":"10.1093\/nar\/gkx1089","article-title":"HMDB 4.0: The human metabolome database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.14336\/AD.2020.0217","article-title":"Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer\u2019s Disease","volume":"11","author":"Shao","year":"2020","journal-title":"Aging Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.jalz.2017.04.009","article-title":"Association of amine biomarkers with incident dementia and Alzheimer\u2019s disease in the Framingham Study","volume":"13","author":"Chouraki","year":"2017","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6995","DOI":"10.1021\/ac0708588","article-title":"Investigations of the Effects of Gender, Diurnal Variation, and Age in Human Urinary Metabolomic Profiles","volume":"79","author":"Slupsky","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s11306-007-0091-1","article-title":"Variation of metabolites in normal human urine","volume":"3","author":"Saude","year":"2007","journal-title":"Metabolomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14843","DOI":"10.1038\/srep14843","article-title":"Diurnal rhythms in the human urine metabolome during sleep and total sleep deprivation","volume":"5","author":"Davies","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"953","DOI":"10.7150\/thno.9265","article-title":"Hair metabolomics: Identification of fetal compromise provides proof of concept for biomarker discovery","volume":"4","author":"Sulek","year":"2014","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41598-017-18317-7","article-title":"Analysis of sequential hair segments reflects changes in the metabolome across the trimesters of pregnancy","volume":"8","author":"Delplancke","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s10020-020-00160-8","article-title":"Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow","volume":"26","author":"Yang","year":"2020","journal-title":"Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0379-0738(93)90255-9","article-title":"Anatomy and physiology of hair","volume":"63","author":"Harkey","year":"1993","journal-title":"Forensic Sci. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E183","DOI":"10.25011\/cim.v30i5.2894","article-title":"Measurement of cortisol in human hair as a biomarker of systemic exposure","volume":"30","author":"Sauve","year":"2007","journal-title":"Clin. Investig. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aca.2014.06.053","article-title":"Sample preparation methods for determination of drugs of abuse in hair samples: A review","volume":"857","author":"Vogliardi","year":"2015","journal-title":"Anal. Chim. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0379-0738(93)90256-A","article-title":"Mechanisms of drug incorporation into hair","volume":"63","author":"Henderson","year":"1993","journal-title":"Forensic Sci. Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jang, W.J., Choi, J.Y., Park, B., Seo, J.H., Seo, Y.H., Lee, S., Jeong, C.H., and Lee, S. (2019). Hair Metabolomics in Animal Studies and Clinical Settings. Molecules, 24.","DOI":"10.3390\/molecules24122195"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121708","DOI":"10.1016\/j.talanta.2020.121708","article-title":"Extraction strategies for tackling complete hair metabolome using LC-HRMS-based analysis","volume":"223","author":"Chang","year":"2021","journal-title":"Talanta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1017\/S1041610297004870","article-title":"Clinical dementia rating: A reliable and valid diagnostic and staging measure for dementia of the Alzheimer type","volume":"9","author":"Morris","year":"1997","journal-title":"Int. Psychogeriatr."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mendez, M. (2022). The Mental Status Examination Handbook, Elsevier.","DOI":"10.1016\/B978-0-323-69489-6.00005-X"},{"key":"ref_25","unstructured":"Legato, M.J. (2004). Principles of Gender-Specific Medicine, Academic Press."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"895","DOI":"10.4155\/bio.13.50","article-title":"Hair as an alternative matrix in bioanalysis","volume":"5","author":"Barbosa","year":"2013","journal-title":"Bioanalysis"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Psychogios, N., Hau, D.D., Peng, J., Guo, A.C., Mandal, R., Bouatra, S., Sinelnikov, I., Krishnamurthy, R., Eisner, R., and Gautam, B. (2011). The human serum metabolome. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016957"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1289\/ehp.1308015","article-title":"The blood exposome and its role in discovering causes of disease","volume":"122","author":"Rappaport","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"97008","DOI":"10.1289\/EHP4713","article-title":"Generating the Blood Exposome Database Using a Comprehensive Text Mining and Database Fusion Approach","volume":"127","author":"Barupal","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/jgs.15069","article-title":"Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer\u2019s Disease: Systematic Review and Network Metaanalysis","volume":"66","author":"Tricco","year":"2018","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15612","DOI":"10.1038\/s41598-020-71832-y","article-title":"Blood biomarkers indicate that the preclinical stages of Alzheimer\u2019s disease present overlapping molecular features","volume":"10","author":"Paris","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40364-018-0119-x","article-title":"Comparative analysis of cerebrospinal fluid metabolites in Alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus in a Japanese cohort","volume":"6","author":"Nagata","year":"2018","journal-title":"Biomark. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Cristofano, A., Sapere, N., La Marca, G., Angiolillo, A., Vitale, M., Corbi, G., Scapagnini, G., Intrieri, M., Russo, C., and Corso, G. (2016). Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer\u2019s Dementia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155694"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1002\/acn3.726","article-title":"A metabolomic approach to identifying biomarkers in blood of Alzheimer\u2019s disease","volume":"6","author":"Lin","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1194\/jlr.R700019-JLR200","article-title":"Phosphatidylcholine and choline homeostasis","volume":"49","author":"Li","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.neurobiolaging.2004.02.016","article-title":"Glycerophosphocholine is elevated in cerebrospinal fluid of Alzheimer patients","volume":"25","author":"Walter","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nm.3466","article-title":"Plasma phospholipids identify antecedent memory impairment in older adults","volume":"20","author":"Mapstone","year":"2014","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.neurobiolaging.2013.08.001","article-title":"Evidence of altered phosphatidylcholine metabolism in Alzheimer\u2019s disease","volume":"35","author":"Whiley","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1007\/s00702-003-0007-9","article-title":"Decreased lysophosphatidylcholine\/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer\u2019s disease","volume":"110","author":"Mulder","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/alz.12484","article-title":"A metabolite panel that differentiates Alzheimer\u2019s disease from other dementia types","volume":"18","author":"Jia","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jnutbio.2019.05.009","article-title":"Piperine attenuates cognitive impairment in an experimental mouse model of sporadic Alzheimer\u2019s disease","volume":"70","author":"Wang","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2012.12.013","article-title":"Endogenous morphine and its metabolites in mammals: History, synthesis, localization and perspectives","volume":"233","author":"Mouheiche","year":"2013","journal-title":"Neuroscience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1046\/j.1365-2362.1999.00511.x","article-title":"Tetrahydropapaveroline, a dopamine-derived isoquinoline alkaloid, undergoes oxidation: Implications for DNA damage and neuronal cell death","volume":"29","author":"Surh","year":"1999","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/S0006-2952(03)00421-0","article-title":"Aggravation of L-DOPA-induced neurotoxicity by tetrahydropapaveroline in PC12 cells","volume":"66","author":"Lee","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/NEN.0b013e3181cb5af4","article-title":"Oxidative stress in the progression of Alzheimer disease in the frontal cortex","volume":"69","author":"Ansari","year":"2010","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/jnen\/60.8.759","article-title":"Oxidative damage is the earliest event in Alzheimer disease","volume":"60","author":"Nunomura","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.mrrev.2003.06.023","article-title":"Oxidative DNA damage and glioma cell death induced by tetrahydropapaveroline","volume":"544","author":"Soh","year":"2003","journal-title":"Mutat. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"63","DOI":"10.5607\/en.2010.19.2.63","article-title":"Neurotoxic effects of tetrahydroisoquinolines and underlying mechanisms","volume":"19","author":"Surh","year":"2010","journal-title":"Exp. Neurobiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1093\/brain\/awr166","article-title":"Endogenous morphine-like compound immunoreactivity increases in parkinsonism","volume":"134","author":"Charron","year":"2011","journal-title":"Brain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.pbb.2015.09.008","article-title":"Inhibition of phosphorylated tyrosine hydroxylase attenuates ethanol-induced hyperactivity in adult zebrafish (Danio rerio)","volume":"138","author":"Nowicki","year":"2015","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1007\/s12640-019-00051-9","article-title":"Not Just from Ethanol. Tetrahydroisoquinolinic (TIQ) Derivatives: From Neurotoxicity to Neuroprotection","volume":"36","author":"Peana","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1471-4159.2006.03756.x","article-title":"The mechanism of 1,2,3,4-tetrahydroisoquinolines neuroprotection: The importance of free radicals scavenging properties and inhibition of glutamate-induced excitotoxicity","volume":"97","author":"Lazarewicz","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_53","first-page":"64","article-title":"Contrasting effects of catecholic and O-methylated tetrahydroisoquinolines on hydroxyl radical production","volume":"1434","author":"Nappi","year":"1999","journal-title":"Biochim. Biophys. Acta BBA-Protein Struct. Mol. Enzymol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137267","DOI":"10.1016\/j.scitotenv.2020.137267","article-title":"Exposure of ultrafine particulate matter causes glutathione redox imbalance in the hippocampus: A neurometabolic susceptibility to Alzheimer\u2019s pathology","volume":"718","author":"Park","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.forsciint.2011.10.024","article-title":"Society of Hair Testing guidelines for drug testing in hair","volume":"218","author":"Cooper","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7946","DOI":"10.1021\/acs.analchem.6b00770","article-title":"Hydrogen Rearrangement Rules: Computational MS\/MS Fragmentation and Structure Elucidation Using MS-FINDER Software","volume":"88","author":"Tsugawa","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2166\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:42:46Z","timestamp":1760121766000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/5\/2166"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,25]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["molecules28052166"],"URL":"https:\/\/doi.org\/10.3390\/molecules28052166","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,25]]}}}