{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:51:40Z","timestamp":1790751100714,"version":"4.1.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007051","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>This study evaluated the cerebrospinal fluid (CSF) proteomes from 31 patients diagnosed with myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS). We quantified 902 proteins, each expressed in at least eleven samples, and systematically categorized clinical factors relevant to ME\/CFS symptoms\u2014including autonomic dysfunction, neuroinflammation and metabolic disturbances. Differentially expressed protein and pathway analyses evaluated protein features associated with both postural orthostatic tachycardia syndrome (POTS) status and disease severity among the patients, while ratio-based analysis further explored associations with severity ratings. Data are available via ProteomeXchange with identifier PXD076216. Neutrophil degranulation and platelet activation were enriched in patients with POTS, and several pathways, such as the complement cascade, coagulation-related pathways and IGFBP\u2011mediated insulin-like growth factor transport, were enriched in severe cases. Ratio-based analysis identified four biologically interpretable severity-associated protein ratios related to cellular stress, extracellular remodelling and immune\u2013neuronal interaction. Together, these findings provide insight into the biological processes associated with clinical heterogeneity in ME\/CFS and generate hypotheses for future validation in larger independent cohorts.<\/jats:p>","DOI":"10.1038\/s41598-026-46965-1","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T03:04:50Z","timestamp":1775185490000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic signatures in cerebrospinal fluid and their clinical associations in patients with ME\/CFS"],"prefix":"10.1038","volume":"16","author":[{"given":"Bj\u00f6rn","family":"Brag\u00e9e","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Meadows","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Widgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Sj\u00f6gren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Hamid","family":"Ghatan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo C.","family":"Bertilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhong","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Bergquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"46965_CR1","unstructured":"CDC. Fast Facts: ME\/CFS. Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome https:\/\/www.cdc.gov\/me-cfs\/about\/fast-facts-about-me-cfs.html. (2024)."},{"key":"46965_CR2","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s12967-020-02269-0","volume":"18","author":"E-J Lim","year":"2020","unstructured":"Lim, E.-J. et al. Systematic review and meta-analysis of the prevalence of Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis (CFS\/ME). J. Transl. Med. 18, 100 (2020).","journal-title":"J. Transl. Med."},{"key":"46965_CR3","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1038\/s41591-024-03173-6","volume":"30","author":"Z Al-Aly","year":"2024","unstructured":"Al-Aly, Z. et al. Long COVID science, research and policy. Nat. Med. 30, 2148\u20132164 (2024).","journal-title":"Nat. Med."},{"key":"46965_CR4","doi-asserted-by":"publisher","first-page":"106297","DOI":"10.1016\/j.jinf.2024.106297","volume":"89","author":"A Dehlia","year":"2024","unstructured":"Dehlia, A. & Guthridge, M. A. The persistence of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (ME\/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis. J. Infect. 89, 106297 (2024).","journal-title":"J. Infect."},{"key":"46965_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1300\/J092v11n01_02","volume":"11","author":"BM Carruthers","year":"2003","unstructured":"Carruthers, B. M. et al. Myalgic encephalomyelitis\/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols. J. Chronic Fatigue Syndr. 11, 7\u2013115 (2003).","journal-title":"J. Chronic Fatigue Syndr."},{"key":"46965_CR6","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1016\/j.mayocp.2021.07.004","volume":"96","author":"L Bateman","year":"2021","unstructured":"Bateman, L. et al. Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Essentials of diagnosis and management. Mayo Clin. Proc. 96, 2861\u20132878 (2021).","journal-title":"Mayo Clin. Proc."},{"key":"46965_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s43587-023-00550-7","volume":"4","author":"BM Tijms","year":"2024","unstructured":"Tijms, B. M. et al. Cerebrospinal fluid proteomics in patients with Alzheimer\u2019s disease reveals five molecular subtypes with distinct genetic risk profiles. Nat. Aging 4, 33\u201347 (2024).","journal-title":"Nat. Aging"},{"key":"46965_CR8","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1002\/alz.12713","volume":"19","author":"A Delvenne","year":"2023","unstructured":"Delvenne, A. et al. Cerebrospinal fluid proteomic profiling of individuals with mild cognitive impairment and suspected non-Alzheimer\u2019s disease pathophysiology. Alzheimers Dement. J. Alzheimers Assoc. 19, 807\u2013820 (2023).","journal-title":"Alzheimers Dement. J. Alzheimers Assoc."},{"key":"46965_CR9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12987-024-00515-x","volume":"21","author":"C Mirian","year":"2024","unstructured":"Mirian, C. et al. Mass spectrometry-based proteomics of cerebrospinal fluid in pediatric central nervous system malignancies: A systematic review with meta-analysis of individual patient data. Fluids Barriers CNS 21, 14 (2024).","journal-title":"Fluids Barriers CNS"},{"key":"46965_CR10","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1186\/s12967-021-03143-3","volume":"19","author":"KJ Wirth","year":"2021","unstructured":"Wirth, K. J., Scheibenbogen, C. & Paul, F. An attempt to explain the neurological symptoms of Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. J. Transl. Med. 19, 471 (2021).","journal-title":"J. Transl. Med."},{"key":"46965_CR11","doi-asserted-by":"publisher","first-page":"7381","DOI":"10.1038\/s41598-025-91324-1","volume":"15","author":"JN Baraniuk","year":"2025","unstructured":"Baraniuk, J. N. Cerebrospinal fluid metabolomics, lipidomics and serine pathway dysfunction in Myalgic Encephalomyelitis\/Chronic Fatigue Syndroome (ME\/CFS). Sci. Rep. 15, 7381 (2025).","journal-title":"Sci. Rep."},{"key":"46965_CR12","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/mp.2015.29","volume":"21","author":"M Hornig","year":"2016","unstructured":"Hornig, M. et al. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis\/chronic fatigue syndrome. Mol. Psychiatry 21, 261\u2013269 (2016).","journal-title":"Mol. Psychiatry"},{"key":"46965_CR13","first-page":"52","volume":"12","author":"BH Natelson","year":"2005","unstructured":"Natelson, B. H., Weaver, S. A., Tseng, C.-L. & Ottenweller, J. E. Spinal fluid abnormalities in patients with chronic fatigue syndrome. Clin. Diagn. Lab. Immunol. 12, 52\u201355 (2005).","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"46965_CR14","doi-asserted-by":"publisher","DOI":"10.1093\/jimmun\/vkaf087","author":"VC Bastos","year":"2025","unstructured":"Bastos, V. C. et al. Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis\/chronic fatigue syndrome. J. Immunol. https:\/\/doi.org\/10.1093\/jimmun\/vkaf087 (2025).","journal-title":"J. Immunol."},{"key":"46965_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017287","author":"SE Schutzer","year":"2011","unstructured":"Schutzer, S. E. et al. Distinct cerebrospinal fluid proteomes differentiate post-treatment lyme disease from chronic fatigue syndrome. PLoS ONE https:\/\/doi.org\/10.1371\/journal.pone.0017287 (2011).","journal-title":"PLoS ONE"},{"key":"46965_CR16","doi-asserted-by":"publisher","first-page":"2208372","DOI":"10.1080\/07853890.2023.2208372","volume":"55","author":"SE Schutzer","year":"2023","unstructured":"Schutzer, S. E. et al. Myalgic encephalomyelitis\/chronic fatigue syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes. Ann. Med. 55, 2208372 (2023).","journal-title":"Ann. Med."},{"key":"46965_CR17","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1038\/nature03985","volume":"437","author":"SE Calvano","year":"2005","unstructured":"Calvano, S. E. et al. A network-based analysis of systemic inflammation in humans. Nature 437, 1032\u20131037 (2005).","journal-title":"Nature"},{"key":"46965_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03565-2","author":"HS-H Oh","year":"2025","unstructured":"Oh, H.S.-H. et al. A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer\u2019s disease. Nat. Med. https:\/\/doi.org\/10.1038\/s41591-025-03565-2 (2025).","journal-title":"Nat. Med."},{"key":"46965_CR19","unstructured":"The brain reacting to COVID-19: analysis of the cerebrospinal fluid proteome, RNA and inflammation - PMC. https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC9909638\/."},{"key":"46965_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.567537","author":"D Chung","year":"2020","unstructured":"Chung, D., Shum, A. & Caraveo, G. GAP-43 and BASP1 in axon regeneration: implications for the treatment of neurodegenerative diseases. Front. Cell Dev. Biol. https:\/\/doi.org\/10.3389\/fcell.2020.567537 (2020).","journal-title":"Front. Cell Dev. Biol."},{"key":"46965_CR21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jalz.2018.08.006","volume":"15","author":"\u00c5 Sandelius","year":"2019","unstructured":"Sandelius, \u00c5. et al. Elevated CSF GAP-43 is Alzheimer\u2019s disease specific and associated with tau and amyloid pathology. Alzheimers Dement. J. Alzheimers Assoc. 15, 55\u201364 (2019).","journal-title":"Alzheimers Dement. J. Alzheimers Assoc."},{"key":"46965_CR22","doi-asserted-by":"publisher","first-page":"948160","DOI":"10.3389\/fnmol.2022.948160","volume":"15","author":"C Yan","year":"2022","unstructured":"Yan, C., Jiang, J., Yang, Y., Geng, X. & Dong, W. The function of VAMP2 in mediating membrane fusion: An overview. Front. Mol. Neurosci. 15, 948160 (2022).","journal-title":"Front. Mol. Neurosci."},{"key":"46965_CR23","doi-asserted-by":"publisher","first-page":"4189","DOI":"10.1007\/s12035-016-9997-9","volume":"54","author":"Q Zheng","year":"2017","unstructured":"Zheng, Q. et al. The neuron-specific protein TMEM59L mediates oxidative stress-induced cell death. Mol. Neurobiol. 54, 4189\u20134200 (2017).","journal-title":"Mol. Neurobiol."},{"key":"46965_CR24","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1016\/j.cell.2019.04.008","volume":"177","author":"H Song","year":"2019","unstructured":"Song, H. et al. Molecular basis of arthritogenic alphavirus receptor MXRA8 binding to Chikungunya Virus envelope protein. Cell 177, 1714-1724.e12 (2019).","journal-title":"Cell"},{"key":"46965_CR25","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1016\/j.celrep.2019.07.105","volume":"28","author":"R Zhang","year":"2019","unstructured":"Zhang, R. et al. Expression of the Mxra8 receptor promotes alphavirus infection and pathogenesis in mice and drosophila. Cell Rep. 28, 2647-2658.e5 (2019).","journal-title":"Cell Rep."},{"key":"46965_CR26","doi-asserted-by":"publisher","first-page":"e0206478","DOI":"10.1371\/journal.pone.0206478","volume":"13","author":"LM Schilde","year":"2018","unstructured":"Schilde, L. M. et al. Protein variability in cerebrospinal fluid and its possible implications for neurological protein biomarker research. PLoS ONE 13, e0206478 (2018).","journal-title":"PLoS ONE"},{"key":"46965_CR27","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1074\/mcp.TIR120.002155","volume":"19","author":"J Griss","year":"2020","unstructured":"Griss, J. et al. ReactomeGSA - Efficient multi-omics comparative pathway analysis. Mol. Cell. Proteomics 19, 2115\u20132125 (2020).","journal-title":"Mol. Cell. Proteomics"},{"key":"46965_CR28","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.chest.2022.04.146","volume":"162","author":"P Joseph","year":"2022","unstructured":"Joseph, P. et al. Neurovascular dysregulation and acute exercise intolerance in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome. Chest 162, 1116\u20131126 (2022).","journal-title":"Chest"},{"key":"46965_CR29","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41467-024-45107-3","volume":"15","author":"B Walitt","year":"2024","unstructured":"Walitt, B. et al. Deep phenotyping of post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome. Nat. Commun. 15, 907 (2024).","journal-title":"Nat. Commun."},{"key":"46965_CR30","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1210\/endrev\/bnad008","volume":"44","author":"RC Baxter","year":"2023","unstructured":"Baxter, R. C. Signaling pathways of the insulin-like growth factor binding proteins. Endocr. Rev. 44, 753\u2013778 (2023).","journal-title":"Endocr. Rev."},{"key":"46965_CR31","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.dld.2014.05.013","volume":"46","author":"A Negroni","year":"2014","unstructured":"Negroni, A. et al. Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease. Dig. Liver Dis. 46, 788\u2013794 (2014).","journal-title":"Dig. Liver Dis."},{"key":"46965_CR32","doi-asserted-by":"publisher","first-page":"109688","DOI":"10.1016\/j.biopha.2019.109688","volume":"122","author":"Z Wang","year":"2020","unstructured":"Wang, Z., Zhang, H. & Cheng, Q. PDIA4: The basic characteristics, functions and its potential connection with cancer. Biomed. Pharmacother. 122, 109688 (2020).","journal-title":"Biomed. Pharmacother."},{"key":"46965_CR33","doi-asserted-by":"publisher","first-page":"1053882","DOI":"10.3389\/fendo.2022.1053882","volume":"13","author":"C-H Lee","year":"2022","unstructured":"Lee, C.-H. et al. PDIA4, a new endoplasmic reticulum stress protein, modulates insulin resistance and inflammation in skeletal muscle. Front. Endocrinol. 13, 1053882 (2022).","journal-title":"Front. Endocrinol."},{"key":"46965_CR34","first-page":"792","volume":"1831","author":"CC Lord","year":"2013","unstructured":"Lord, C. C., Thomas, G. & Brown, J. M. Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism. Biochim. Biophys. Acta BBA Mol. Cell Biol. Lipids 1831, 792\u2013802 (2013).","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Biol. Lipids"},{"key":"46965_CR35","doi-asserted-by":"publisher","first-page":"180017","DOI":"10.1098\/rsob.180017","volume":"8","author":"J Xu","year":"2018","unstructured":"Xu, J. et al. Sequence analysis and structure prediction of ABHD16A and the roles of the ABHD family members in human disease. Open Biol. 8, 180017 (2018).","journal-title":"Open Biol."},{"key":"46965_CR36","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1021\/acschembio.7b00885","volume":"12","author":"ST Cheung","year":"2017","unstructured":"Cheung, S. T. et al. Discovery of a small-molecule modulator of glycosaminoglycan sulfation. ACS Chem. Biol. 12, 3126\u20133133 (2017).","journal-title":"ACS Chem. Biol."},{"key":"46965_CR37","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.bbrc.2010.10.084","volume":"402","author":"C Peng","year":"2010","unstructured":"Peng, C. et al. Identification of a novel human UDP-GalNAc transferase with unique catalytic activity and expression profile. Biochem. Biophys. Res. Commun. 402, 680\u2013686 (2010).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"46965_CR38","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1186\/s12935-024-03492-1","volume":"24","author":"X Sun","year":"2024","unstructured":"Sun, X. et al. GALNT6 promotes bladder cancer malignancy and immune escape by epithelial-mesenchymal transition and CD8+ T cells. Cancer Cell Int. 24, 308 (2024).","journal-title":"Cancer Cell Int."},{"key":"46965_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3892\/mco.2025.2832","volume":"22","author":"C Miao","year":"2025","unstructured":"Miao, C. et al. Mechanism of the GALNT family proteins in regulating tumorigenesis and development of lung cancer (review). Mol. Clin. Oncol. 22, 1\u20139 (2025).","journal-title":"Mol. Clin. Oncol."},{"key":"46965_CR40","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.18632\/oncotarget.27634","volume":"11","author":"S Bhattacharyya","year":"2020","unstructured":"Bhattacharyya, S. et al. Increased CHST15 follows decline in arylsulfatase B (ARSB) and disinhibition of non-canonical WNT signaling: Potential impact on epithelial and mesenchymal identity. Oncotarget 11, 2327\u20132344 (2020).","journal-title":"Oncotarget"},{"key":"46965_CR41","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.molimm.2003.12.002","volume":"40","author":"AM Blom","year":"2004","unstructured":"Blom, A. M., Villoutreix, B. O. & Dahlb\u00e4ck, B. Complement inhibitor C4b-binding protein\u2014friend or foe in the innate immune system?. Mol. Immunol. 40, 1333\u20131346 (2004).","journal-title":"Mol. Immunol."},{"key":"46965_CR42","doi-asserted-by":"publisher","first-page":"e46773","DOI":"10.7554\/eLife.46773","volume":"8","author":"X Meng","year":"2019","unstructured":"Meng, X. et al. Neurexophilin4 is a selectively expressed \u03b1-neurexin ligand that modulates specific cerebellar synapses and motor functions. Elife 8, e46773 (2019).","journal-title":"Elife"},{"key":"46965_CR43","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ajmg.c.31552","volume":"175","author":"F Malfait","year":"2017","unstructured":"Malfait, F. et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am. J. Med. Genet. C Semin. Med. Genet. 175, 8\u201326 (2017).","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"46965_CR44","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s10286-011-0119-5","volume":"21","author":"R Freeman","year":"2011","unstructured":"Freeman, R. et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin. Auton. Res. 21, 69\u201372 (2011).","journal-title":"Clin. Auton. Res."},{"key":"46965_CR45","unstructured":"MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. https:\/\/www.nature.com\/articles\/nbt.1511."},{"key":"46965_CR46","doi-asserted-by":"publisher","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","volume":"51","author":"The UniProt Consortium","year":"2023","unstructured":"The UniProt Consortium. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res. 51, D523\u2013D531 (2023).","journal-title":"Nucleic Acids Res."},{"key":"46965_CR47","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"Ggplot2","author":"H Wickham","year":"2016","unstructured":"Wickham, H. Ggplot2 (Springer International Publishing, 2016). https:\/\/doi.org\/10.1007\/978-3-319-24277-4."},{"issue":"Suppl 1","key":"46965_CR48","doi-asserted-by":"publisher","first-page":"S96","DOI":"10.1093\/bioinformatics\/18.suppl_1.S96","volume":"18","author":"W Huber","year":"2002","unstructured":"Huber, W., von Heydebreck, A., S\u00fcltmann, H., Poustka, A. & Vingron, M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinforma. Oxf. Engl. 18(Suppl 1), S96-104 (2002).","journal-title":"Bioinforma. Oxf. Engl."},{"key":"46965_CR49","unstructured":"Proteome-wide identification of ubiquitin interactions using UbIA-MS. Nat. Protoc. https:\/\/www.nature.com\/articles\/nprot.2017.147."},{"key":"46965_CR50","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"46965_CR51","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kr\u00e4mer","year":"2014","unstructured":"Kr\u00e4mer, A., Green, J., Pollard, J. & Tugendreich, S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinforma. Oxf. Engl. 30, 523\u2013530 (2014).","journal-title":"Bioinforma. Oxf. Engl."},{"key":"46965_CR52","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"Y Benjamini","year":"1995","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. 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"46965_CR53","doi-asserted-by":"publisher","unstructured":"John D. Storey with contributions from Andrew J. Bass, A. qvalue. Bioconductor https:\/\/doi.org\/10.18129\/B9.BIOC.QVALUE (2017).","DOI":"10.18129\/B9.BIOC.QVALUE"},{"key":"46965_CR54","doi-asserted-by":"publisher","unstructured":"Perez-Riverol Y. et al. ThePRIDE database at 20 years: 2025 update. Nucleic Acids Res. 6;53(1):543\u2013553, PMID: 39494541. https:\/\/doi.org\/10.1093\/nar\/gkae1011 (2025).","DOI":"10.1093\/nar\/gkae1011"},{"key":"46965_CR55","doi-asserted-by":"publisher","unstructured":"Deutsch EW. et al. The ProteomeXchange consortium in 2026:making proteomics data FAIR. Nucleic Acids Res. 6;54(1):459\u2013469, PMID: 41206473.https:\/\/doi.org\/10.1093\/nar\/gkaf1146 (2026).","DOI":"10.1093\/nar\/gkaf1146"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46965-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46965-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46965-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:07:56Z","timestamp":1779354476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-46965-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["46965"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-46965-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"26 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15848"}}