{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:18:18Z","timestamp":1785410298486,"version":"3.56.0"},"reference-count":54,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["No. 22-75-10140"],"award-info":[{"award-number":["No. 22-75-10140"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["No. 25-44-02156"],"award-info":[{"award-number":["No. 25-44-02156"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No. 22-75-10140"],"award-info":[{"award-number":["No. 22-75-10140"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]},{"award":["No. 25-44-02156"],"award-info":[{"award-number":["No. 25-44-02156"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB\/C mouse model (n = 59), with acute direct toxic liver injury (DTLI) induced by the administration of streptozotocin (STZ) (100 mg\/kg) in combination with a high-fat and high-fructose diet (HFFD). The hepatoprotective activity of activated hydrolytic lignin (Bp-Cx-1), methanolic fraction of Bp-Cx-1 (Bp-Cx-M) and isoflavones from kudzu Pueraria lobata roots (IFL) were evaluated on molecular level using mass spectrometry (MS)-based omics technologies. Untargeted label-free DIA quantitation resulted in 7214 protein groups identification (FDR 1%) after filtering across 40 liver tissue extracts. All treatment groups were closer to the control samples on the liver proteomic landscape compared to the untreated DTLI group, with the best results shown for the Bp-Cx-M and IFL groups. In order to identify differences between specific groups, we applied the post hoc Dunn\u2019s test and used Hedges\u2019 g as the effect size metric, revealing 64 proteins that tended to return to their normal level after treatment. In-depth proteomic liver tissue analysis enabled us not only to reveal the main pathways such as inflammation and oxidative stress, which are in a good agreement with DTLI and non-alcoholic liver disease pathophysiology, but also to evaluate hepatoprotective activity of multicomponent mixtures of natural origin containing polyphenols and mostly associated with protein metabolism (e.g., PSMD7, HCFC1) and deubiquitination pathways (e.g., UCHL3). It is worth noting that the Bp-Cx-1 isolated methanol fraction (Bp-Cx-M) demonstrated a pronounced increased hepatoprotective activity compared to the parent material due to the enrichment with active components such as polyphenols. Consistent with the proteomic findings of restored ubiquitin\u2013proteasome function, assessment by comet assay revealed that treatments with Bp-Cx-M and IFL significantly reduced DNA damage by 50% compared to the untreated DTLI group. The developed MS-based multi-omics approach may be implemented for the robust and high-throughput screening method during assessment of new hepatoprotective agents of synthetic or natural origin.<\/jats:p>","DOI":"10.3390\/ijms27146148","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"6148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols"],"prefix":"10.3390","volume":"27","author":[{"given":"Alexander G.","family":"Brzhozovskiy","sequence":"first","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"},{"name":"Centre for Applied Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, P.O. 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Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1515-9447","authenticated-orcid":false,"given":"Anna E.","family":"Bugrova","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-0079","authenticated-orcid":false,"given":"Natalia V.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8177-7449","authenticated-orcid":false,"given":"Maria I.","family":"Indeykina","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"},{"name":"Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria A.","family":"Kharina","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-9245","authenticated-orcid":false,"given":"Oxana A.","family":"Kovaleva","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3481-4606","authenticated-orcid":false,"given":"Alexander Y.","family":"Zherebker","sequence":"additional","affiliation":[{"name":"The Center for Bio- and Medical Technologies, 121205 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-9843","authenticated-orcid":false,"given":"Elena I.","family":"Fedoros","sequence":"additional","affiliation":[{"name":"N.N. 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Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, J., Tian, C., Liu, M., Guo, H., Lin, F., Ding, Y., Yao, W., Zhang, J., Fan, J., and Yu, C. (2024). Genetic Risk, BMI Status, BMI Change Patterns, and the Risk of Steatotic Liver Disease and Liver Enzyme Elevation in Chinese Adults. Nutrients, 16.","DOI":"10.3390\/nu16234212"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41575-020-0316-6","article-title":"From NAFLD to MAFLD: When Pathophysiology Succeeds","volume":"17","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A New Definition for Metabolic Dysfunction-Associated Fatty Liver Disease: An International Expert Consensus Statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1053\/jhep.2003.50161","article-title":"Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome","volume":"37","author":"Marchesini","year":"2003","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Martinou, E., Pericleous, M., Stefanova, I., Kaur, V., and Angelidi, A.M. (2022). Diagnostic Modalities of Non-Alcoholic Fatty Liver Disease: From Biochemical Biomarkers to Multi-Omics Non-Invasive Approaches. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020407"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2016). EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The Multiple-Hit Pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.cld.2009.07.009","article-title":"Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis","volume":"13","author":"Cusi","year":"2009","journal-title":"Clin. Liver Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cld.2017.08.007","article-title":"V Pathophysiology of Nonalcoholic Fatty Liver Disease\/Nonalcoholic Steatohepatitis","volume":"22","author":"Manne","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_11","first-page":"4948","article-title":"Germ-Free C57BL\/6J Mice Are Resistant to High-Fat-Diet-Induced Insulin Resistance and Have Altered Cholesterol Metabolism","volume":"24","author":"Rabot","year":"2010","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1136\/gutjnl-2012-303816","article-title":"Intestinal Microbiota Determines Development of Non-Alcoholic Fatty Liver Disease in Mice","volume":"62","author":"Llopis","year":"2013","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"619","DOI":"10.4254\/wjh.v11.i8.619","article-title":"Prolonged High-Fat-Diet Feeding Promotes Non-Alcoholic Fatty Liver Disease and Alters Gut Microbiota in Mice","volume":"11","author":"Enos","year":"2019","journal-title":"World J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cels.2017.12.006","article-title":"Integration of Multi-Omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-Alcoholic Fatty Liver Disease","volume":"6","author":"Kurt","year":"2018","journal-title":"Cell Syst."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/bph.14095","article-title":"Tauroursodeoxycholic Acid Inhibits Intestinal Inflammation and Barrier Disruption in Mice with Non-Alcoholic Fatty Liver Disease","volume":"175","author":"Wang","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejphar.2008.01.045","article-title":"Ezetimibe Improves High Fat and Cholesterol Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice","volume":"584","author":"Zheng","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alqahtani, Q.H., Alshehri, S., Alhusaini, A.M., Sarawi, W.S., Alqarni, S.S., Mohamed, R., Kumar, M.N., Al-Saab, J., and Hasan, I.H. (2023). Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms. Diseases, 11.","DOI":"10.3390\/diseases11040184"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1034\/j.1600-6143.2003.00040.x","article-title":"The Effect of Low Versus High Dose of Streptozotocin in Cynomolgus Monkeys (Macaca Fascilularis)","volume":"3","author":"Koulmanda","year":"2003","journal-title":"Am. J. Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/hep.31056","article-title":"Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD","volume":"72","author":"Carpino","year":"2020","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100129","DOI":"10.1016\/j.labinv.2023.100129","article-title":"Comparison of Animal Models for the Study of Nonalcoholic Fatty Liver Disease","volume":"103","author":"Zheng","year":"2023","journal-title":"Lab. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1007\/s00125-016-4084-3","article-title":"Hepatocyte Glutathione Peroxidase-1 Deficiency Improves Hepatic Glucose Metabolism and Decreases Steatohepatitis in Mice","volume":"59","author":"Merry","year":"2016","journal-title":"Diabetologia"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Brzhozovskiy, A.G., Semenov, S.D., Zherebker, A.Y., Bugrova, A.E., Yurova, M.N., Zhernov, Y.V., Kovaleva, O.A., Semenov, A.L., Abroskin, D.P., and Kruglov, S.S. (2025). Hepatoprotective Activity of Nature-Derived Polyphenols Studied by Mass Spectrometry Based Multi-OMICS Approach. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041604"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1016\/j.cmet.2024.07.014","article-title":"Amelioration of Nonalcoholic Fatty Liver Disease by Inhibiting the Deubiquitylating Enzyme RPN11","volume":"36","author":"Zhou","year":"2024","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1038\/s12276-023-01036-7","article-title":"Ablation of the Deubiquitinase USP15 Ameliorates Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"55","author":"Baek","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1432-1033.1992.tb16961.x","article-title":"Demonstration That a Human 26S Proteolytic Complex Consists of a Proteasome and Multiple Associated Protein Components and Hydrolyzes ATP and Ubiquitin-Ligated Proteins by Closely Linked Mechanisms","volume":"206","author":"Kanayama","year":"1992","journal-title":"Eur. J. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2353\/ajpath.2006.060085","article-title":"Photoreceptor Cell Apoptosis in the Retinal Degeneration of Uchl3-Deficient Mice","volume":"169","author":"Sano","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s, C.M.C., P\u00e9rez de la Lastra, J.M., Andr\u00e9s Juan, C., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. (2023). Superoxide Anion Chemistry-Its Role at the Core of the Innate Immunity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031841"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/S0891-5849(00)00161-1","article-title":"Mitochondrial Oxidative Stress in Mice Lacking the Glutathione Peroxidase-1 Gene","volume":"28","author":"Esposito","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/0003-9861(91)90048-N","article-title":"Characterization and Partial Amino Acid Sequence of Human Plasma Glutathione Peroxidase","volume":"286","author":"Esworthy","year":"1991","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sun, C., Guo, Y., Cong, P., Tian, Y., and Gao, X. (2023). Liver Lipidomics Analysis Revealed the Novel Ameliorative Mechanisms of L-Carnitine on High-Fat Diet-Induced NAFLD Mice. Nutrients, 15.","DOI":"10.3390\/nu15061359"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jhep.2010.10.039","article-title":"Diabetes Is a Progression Factor for Hepatic Fibrosis in a High Fat Fed Mouse Obesity Model of Non-Alcoholic Steatohepatitis","volume":"55","author":"Lo","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e38625","DOI":"10.1016\/j.heliyon.2024.e38625","article-title":"Protective Activity of Hirsutidin in High-Fat Intake and Streptozotocin-Induced Diabetic Rats: In Silico and in Vivo Study","volume":"10","author":"Almalki","year":"2024","journal-title":"Heliyon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6506","DOI":"10.1038\/s41467-024-50660-y","article-title":"A Male Mouse Model for Metabolic Dysfunction-Associated Steatotic Liver Disease and Hepatocellular Carcinoma","volume":"15","author":"Jeong","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.apsb.2025.01.010","article-title":"The Ubiquitin-Proteasome System: A Potential Target for the MASLD","volume":"15","author":"Liu","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Allameh, A., Niayesh-Mehr, R., Aliarab, A., Sebastiani, G., and Pantopoulos, K. (2023). Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12091653"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.18632\/aging.100967","article-title":"Reduced SOD2 Expression Is Associated with Mortality of Hepatocellular Carcinoma Patients in a Mutant P53-Dependent Manner","volume":"8","author":"Wang","year":"2016","journal-title":"Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1021\/acs.jproteome.7b00467","article-title":"The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays","volume":"16","author":"Schwenk","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nmeth.2763","article-title":"Demonstrating the Feasibility of Large-Scale Development of Standardized Assays to Quantify Human Proteins","volume":"11","author":"Kennedy","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e8793","DOI":"10.15252\/msb.20188793","article-title":"Plasma Proteome Profiling Discovers Novel Proteins Associated with Non-Alcoholic Fatty Liver Disease","volume":"15","author":"Niu","year":"2019","journal-title":"Mol. Syst. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.jhep.2012.05.024","article-title":"Mitochondrial GSH Determines the Toxic or Therapeutic Potential of Superoxide Scavenging in Steatohepatitis","volume":"57","author":"Matias","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"114764","DOI":"10.1016\/j.bcp.2021.114764","article-title":"Ubiquitin Pathways Regulate the Pathogenesis of Chronic Liver Disease","volume":"193","author":"Park","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.21037\/tgh-20-125","article-title":"Mitochondrial Dysfunction in Nonalcoholic Fatty Liver Disease and Alcohol Related Liver Disease","volume":"6","author":"Prasun","year":"2021","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"794997","DOI":"10.3389\/fphar.2021.794997","article-title":"Targeting Oxidative Stress as a Therapeutic Approach for Idiopathic Pulmonary Fibrosis","volume":"12","author":"Estornut","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Deng, Y., Dong, Y., Zhang, S., and Feng, Y. (2024). Targeting Mitochondrial Homeostasis in the Treatment of Non-Alcoholic Fatty Liver Disease: A Review. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1463187"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Berardo, C., Di Pasqua, L.G., Cagna, M., Richelmi, P., Vairetti, M., and Ferrigno, A. (2020). Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis: Current Issues and Future Perspectives in Preclinical and Clinical Research. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249646"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"18578","DOI":"10.18632\/oncotarget.24990","article-title":"Novel Water-Soluble Lignin Derivative BP-Cx-1: Identification of Components and Screening of Potential Targets in Silico and in Vitro","volume":"9","author":"Fedoros","year":"2018","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Semenov, A.L., Gubareva, E.A., Ermakova, E.D., Dorofeeva, A.A., Tumanyan, I.A., Radetskaya, E.A., Yurova, M.N., Aboushanab, S.A., Kanwugu, O.N., and Fedoros, E.I. (2021). Astaxantin and Isoflavones Inhibit Benign Prostatic Hyperplasia in Rats by Reducing Oxidative Stress and Normalizing Ca\/Mg Balance. Plants, 10.","DOI":"10.3390\/plants10122735"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41596-022-00754-y","article-title":"Measuring DNA Modifications with the Comet Assay: A Compendium of Protocols","volume":"18","author":"Collins","year":"2023","journal-title":"Nat. Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: Neural Networks and Interference Correction Enable Deep Proteome Coverage in High Throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.21105\/joss.03021","article-title":"Seaborn: Statistical Data Visualization","volume":"6","author":"Waskom","year":"2021","journal-title":"J. Open Source Softw."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D Graphics Environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_53","unstructured":"McKinney, W. (July, January 28). Data Structures for Statistical Computing in Python. Proceedings of the 9th Python in Science Conference, Austin, TX, USA."},{"key":"ref_54","first-page":"225","article-title":"Missing Features Reconstruction Using a Wasserstein Generative Adversarial Imputation Network","volume":"Volume 12140","author":"Balatsko","year":"2020","journal-title":"Computational Science\u2014ICCS 2020, Proceedings of the 20th International Conference Proceedings, Part IV"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:33:09Z","timestamp":1784089989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":54,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146148"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146148","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]}}}