{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:42:30Z","timestamp":1790808150236,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007379","name":"Fondation pour l'Aide \u00e0 la Recherche sur la Scl\u00e9rose en Plaques","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","award":["2015 R02"],"award-info":[{"award-number":["2015 R02"]}],"id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EBioMedicine"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.ebiom.2021.103429","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T05:40:11Z","timestamp":1623390011000},"page":"103429","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":41,"special_numbering":"C","title":["TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood"],"prefix":"10.1016","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4356-3631","authenticated-orcid":false,"given":"Roberta","family":"Amoriello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Chernigovskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2622-5032","authenticated-orcid":false,"given":"Victor","family":"Greiff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Carnasciali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Massacesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Barilaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Repice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Biagioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Aldinucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo A.","family":"Muraro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Laplaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Lossius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7812-9029","authenticated-orcid":false,"given":"Clara","family":"Ballerini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2021.103429_bib0001","unstructured":"Atlas of MS 2013: Mapping Multiple Sclerosis Around the World. London: Multiple Sclerosis international federation; 2013. MS International Federation."},{"key":"10.1016\/j.ebiom.2021.103429_bib0002","first-page":"1502","article-title":"Multiple sclerosis - ScienceDirect","volume":"372","author":"Compston","year":"2008","journal-title":"Mult Scler"},{"key":"10.1016\/j.ebiom.2021.103429_bib0003","doi-asserted-by":"crossref","first-page":"A387","DOI":"10.1016\/j.autrev.2009.11.010","article-title":"Multiple sclerosis: geoepidemiology, genetics and the environment","volume":"9","author":"Milo","year":"2010","journal-title":"Autoimmun Rev"},{"key":"10.1016\/j.ebiom.2021.103429_bib0004","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1177\/1352458517751861","article-title":"McDonald MS diagnostic criteria: evidence-based revisions","volume":"24","author":"Carroll","year":"2017","journal-title":"Mult Scler J"},{"key":"10.1016\/j.ebiom.2021.103429_bib0005","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1186\/s12883-019-1455-7","article-title":"Increase of CSF inflammatory profile in a case of highly active multiple sclerosis","volume":"19","author":"Magliozzi","year":"2019","journal-title":"BMC Neurol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0006","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1073\/pnas.0308689100","article-title":"Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood","volume":"101","author":"Skulina","year":"2004","journal-title":"Proc Natl Acad Sci"},{"key":"10.1016\/j.ebiom.2021.103429_bib0007","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/brain\/awf059","article-title":"Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients","volume":"125","author":"Jacobsen","year":"2002","journal-title":"Brain"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103429_bib0008","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12896-017-0379-9","article-title":"Overview of methodologies for T-cell receptor repertoire analysis","volume":"17","author":"Rosati","year":"2017","journal-title":"BMC Biotechnol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0009","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1002\/eji.201444662","article-title":"High-throughput sequencing of TCR repertoires in multiple sclerosis reveals intrathecal enrichment of EBV-reactive CD8\u00a0+\u00a0T cells","volume":"44","author":"Lossius","year":"2014","journal-title":"Clin Immunol Eur J Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0010","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1002\/acn3.199","article-title":"Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis","volume":"2","author":"Salou","year":"2015","journal-title":"Ann Clin Trans Neurol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0011","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/acn3.310","article-title":"Intrathecal T-cell clonal expansions in patients with multiple sclerosis","volume":"3","author":"Sousa","year":"2016","journal-title":"Ann Clin Transl Neurol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0012","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3389\/fimmu.2018.00509","article-title":"Detailed characterization of T cell receptor repertoires in Multiple Sclerosis brain lesions","volume":"9","author":"Planas","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0013","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1039\/C9ME00071B","article-title":"Augmenting adaptive immunity: progress and challenges in the quantitative engineering and analysis of adaptive immune receptor repertoires","volume":"4","author":"Brown","year":"2019","journal-title":"Mol Syst Des Eng"},{"issue":"Pt 11","key":"10.1016\/j.ebiom.2021.103429_bib0014","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1093\/brain\/awm214","article-title":"Multiple Sclerosis: T-cell receptor expression in distinct brain regions","volume":"130","author":"Junker","year":"2007","journal-title":"Brain"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103429_bib0015","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00401-017-1744-4","article-title":"Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients","volume":"134","author":"van Nierop","year":"2017","journal-title":"Acta Neuropathol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0016","doi-asserted-by":"crossref","first-page":"11881","DOI":"10.1038\/ncomms11881","article-title":"Robust estimates of overall immune-repertoire diversity from high-throughput measurements on samples","volume":"7","author":"Kaplinsky","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.ebiom.2021.103429_bib0017","series-title":"R: a language and environment for statistical computing","author":"Core Team","year":"2018"},{"key":"10.1016\/j.ebiom.2021.103429_bib0018","series-title":"ggplot2: elegant graphics for data analysis","author":"Hadley","year":"2016"},{"key":"10.1016\/j.ebiom.2021.103429_bib0019","series-title":"ggpubr: \u201cggplot2\u201d based publication ready plots","author":"Kassambara","year":"2018"},{"key":"10.1016\/j.ebiom.2021.103429_bib0020","article-title":"The igraph software package for complex network research","volume":"1695","author":"Csardi","year":"2006","journal-title":"Interjournal Complex Syst"},{"key":"10.1016\/j.ebiom.2021.103429_bib0021","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ebiom.2021.103429_bib0022","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1186\/1471-2105-11-367","article-title":"A flexible R package for nonnegative matrix factorization","volume":"11","author":"Gaujoux","year":"2010","journal-title":"BMC Bioinform"},{"key":"10.1016\/j.ebiom.2021.103429_bib0023","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103429_bib0024","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/biostatistics\/kxv027","article-title":"Methods that remove batch effects while retaining group differences may lead to exaggerated confidence in downstream analyses","volume":"17","author":"Nygaard","year":"2016","journal-title":"Biostatistics"},{"key":"10.1016\/j.ebiom.2021.103429_bib0025","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3389\/fimmu.2020.00559","article-title":"The TCR repertoire reconstitution in Multiple Sclerosis: comparing one-shot and continuous immunosuppressive therapies","volume":"11","author":"Amoriello","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0026","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13073-015-0169-8","article-title":"A bioinformatic framework for immune repertoire diversity profiling enables detection of immunological status","volume":"7","author":"Greiff","year":"2015","journal-title":"Genome Med"},{"key":"10.1016\/j.ebiom.2021.103429_bib0027","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.it.2015.09.006","article-title":"Bioinformatic and statistical analysis of adaptive immune repertoires","volume":"36","author":"Greiff","year":"2015","journal-title":"Trends Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0028","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1038\/s41467-019-09278-8","article-title":"Large-scale network analysis reveals the sequence space architecture of antibody repertoires","volume":"10","author":"Miho","year":"2019","journal-title":"Nat Commun"},{"key":"10.1016\/j.ebiom.2021.103429_bib0029","doi-asserted-by":"crossref","first-page":"e22057","DOI":"10.7554\/eLife.22057","article-title":"T cell receptor repertoires of mice and humans are clustered in similarity networks around conserved public CDR3 sequences","volume":"6","author":"Madi","year":"2017","journal-title":"Elife"},{"key":"10.1016\/j.ebiom.2021.103429_bib0030","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1093\/bioinformatics\/btx286","article-title":"McPAS-TCR: a manually curated catalogue of pathology-associated T cell receptor sequences","volume":"33","author":"Tickotsky","year":"2017","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ebiom.2021.103429_bib0031","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkx760","article-title":"VDJdb: a curated database of T-cell receptor sequences with known antigen specificity","volume":"46","author":"Shugay","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103429_bib0032","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.107882","article-title":"High frequency of shared clonotypes in human T cell receptor repertoires","volume":"32","author":"Soto","year":"2020","journal-title":"Cell Rep"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103429_bib0033","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.celrep.2019.09.025","article-title":"T cell repertoire dynamics during pregnancy in Multiple Sclerosis","volume":"29","author":"Ramien","year":"2019","journal-title":"Cell Rep"},{"issue":"11","key":"10.1016\/j.ebiom.2021.103429_bib0034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004503","article-title":"VDJtools: unifying post-analysis of T cell receptor repertoires","volume":"11","author":"Shugay","year":"2015","journal-title":"PLoS Comput Biol"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103429_bib0035","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1172\/JCI71691","article-title":"T cell repertoire following autologous stem cell transplantation for multiple sclerosis","volume":"124","author":"Muraro","year":"2014","journal-title":"J Clin Invest"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103429_bib0036","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/imr.12665","article-title":"Predicting the spectrum of TCR repertoire sharing with a data-driven model of recombination","volume":"284","author":"Elhanati","year":"2018","journal-title":"Immunol Rev"},{"key":"10.1016\/j.ebiom.2021.103429_bib0037","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.coisb.2019.10.007","article-title":"Selected before selection: a case for inherent antigen bias in the T-cell receptor repertoire","volume":"18","author":"Thomas","year":"2019","journal-title":"Curr Opin Syst Biol"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103429_bib0038","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jtbi.2010.10.001","article-title":"Model for comparative analysis of antigen receptor repertoires","volume":"269","author":"Rempala","year":"2011","journal-title":"J Theor Biol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0039","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1146\/annurev-immunol-042718-041757","article-title":"Using T cell receptor repertoires to understand the principles of adaptive immune recognition","volume":"37","author":"Bradley","year":"2019","journal-title":"Annu Rev Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0040","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.coisb.2020.10.010","article-title":"Mining adaptive immune receptor repertoires for biological and clinical information using machine learning","volume":"24","author":"Greiff","year":"2020","journal-title":"Curr Opin Syst Biol"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103429_bib0041","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jinf.2018.03.014","article-title":"Increased risk of autoimmune diseases in dengue patients: a population-based cohort study","volume":"77","author":"Li","year":"2018","journal-title":"J Infect"},{"issue":"5","key":"10.1016\/j.ebiom.2021.103429_bib0042","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1089\/cmb.2019.0171","article-title":"A graph-based approach for finding the dengue infection pathways in humans using protein-protein interactions","volume":"27","author":"Dey","year":"2020","journal-title":"J Comput Biol"},{"issue":"12","key":"10.1016\/j.ebiom.2021.103429_bib0043","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.tig.2017.09.004","article-title":"The genetics of Multiple Sclerosis: from 0 to 200 in 50 Years","volume":"33","author":"Baranzini","year":"2017","journal-title":"Trends Genet"},{"issue":"10","key":"10.1016\/j.ebiom.2021.103429_bib0044","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1038\/s41588-020-0684-4","article-title":"Complex genetic signatures in immune cells underlie autoimmunity and inform therapy","volume":"52","author":"Orr\u00f9","year":"2020","journal-title":"Nat Genet"},{"key":"10.1016\/j.ebiom.2021.103429_bib0045","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fcimb.2019.00138","article-title":"Exploring the \"Multiple-Hit Hypothesis\" of neurodegenerative disease: bacterial infection comes up to bat","volume":"9","author":"Patrick","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103429_bib0046","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/eji.202048630","article-title":"Broadly reactive human CD4+ T cells against Enterobacteriaceae are found in the na\u00efve repertoire and are clonally expanded in the memory repertoire","volume":"51","author":"Cassotta","year":"2021","journal-title":"Eur J Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0047","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41582-019-0268-z","article-title":"Immune reconstitution therapies: concepts for durable remission in multiple sclerosis","volume":"16","author":"L\u00fcnemann","year":"2020","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0048","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3389\/fimmu.2021.626793","article-title":"The future of blood testing is the immunome","volume":"12","author":"Arnaout","year":"2021","journal-title":"Front Immunol"},{"key":"10.1016\/j.ebiom.2021.103429_bib0049","doi-asserted-by":"crossref","unstructured":"Pavlovi\u0107 M., Scheffer L., Motwani K., Kanduri C., Kompova R., Vazov N. et\u00a0al. immuneML: an ecosystem for machine learning analysis of adaptive immune receptor repertoires. bioRxiv 2021.03.08.433891; https:\/\/doi.org\/10.1101\/2021.03.08.433891.","DOI":"10.1101\/2021.03.08.433891"}],"container-title":["EBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642100222X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S235239642100222X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T19:05:28Z","timestamp":1762455928000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S235239642100222X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":49,"alternative-id":["S235239642100222X"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103429","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TCR repertoire diversity in Multiple Sclerosis: High-dimensional bioinformatics analysis of sequences from brain, cerebrospinal fluid and peripheral blood","name":"articletitle","label":"Article Title"},{"value":"EBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103429","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"103429"}}