{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:10:04Z","timestamp":1779300604508,"version":"3.51.4"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 32200134"],"award-info":[{"award-number":["No. 32200134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the National 370 Key R&D Program of China","award":["No. 2022YFC2305100"],"award-info":[{"award-number":["No. 2022YFC2305100"]}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["No. 2025AFB954"],"award-info":[{"award-number":["No. 2025AFB954"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022810","name":"State Key Laboratory for Advanced Metals and Materials","doi-asserted-by":"publisher","award":["(2024KF00005"],"award-info":[{"award-number":["(2024KF00005"]}],"id":[{"id":"10.13039\/100022810","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Influenza virus A (H1N1) can lead to acute respiratory infection, while Guillain-Barr\u00e9 Syndrome (GBS) is an autoimmune peripheral neuropathy, which can work as a post-infectious disease. There are clinical observations showing the existence of a possible relationship between the presence of H1N1 infection and GBS disease, and therefore there could be common immunopathological pathways associated with H1N1 infection and GBS. The possible similarity between H1N1 infection and GBS was further investigated using integrated bioinformatics and systems biology approaches. Differentially expressed genes (DEGs) were identified from GEO datasets related to H1N1 infection and GBS. Enrichment analysis was conducted to understand the functional roles of identified DEGs by performing GO and KEGG pathway analysis. For the interacting proteins of the common DEGs, protein-protein interaction (PPI) network analysis helped to find out TLR4, TNF, and ITGAM as key hub genes. These hub genes might have common molecular pathways in H1N1 infection and GBS. To predict possible drug targets for treatment, analysis of interactions between hub genes and miRNAs, TFs, and related diseases was performed.<\/jats:p>","DOI":"10.1371\/journal.pone.0349687","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:50:26Z","timestamp":1779299426000},"page":"e0349687","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational biology exposed a common pathogenic mechanism in influenza A and Guillain-Barr\u00e9 syndrome"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6163-4760","authenticated-orcid":true,"given":"Ye","family":"Deng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongwen","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xujuan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiongya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8779-0353","authenticated-orcid":true,"given":"Fuli","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"issue":"25","key":"pone.0349687.ref001","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1056\/NEJMoa0903810","article-title":"Emergence of a novel swine-origin influenza A (H1N1) virus in humans","volume":"360","author":"Team Novel Swine-Origin Influenza A (H1N1) Virus Investigation","year":"2009","journal-title":"N Engl J Med"},{"issue":"5934","key":"pone.0349687.ref002","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1126\/science.1176062","article-title":"Pandemic potential of a strain of influenza A (H1N1): Early findings","volume":"324","author":"C Fraser","year":"2009","journal-title":"Science"},{"issue":"3","key":"pone.0349687.ref003","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1056\/NEJMra0904322","article-title":"Historical perspective--Emergence of influenza A (H1N1) viruses","volume":"361","author":"SM Zimmer","year":"2009","journal-title":"N Engl J Med"},{"issue":"9497","key":"pone.0349687.ref004","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/S0140-6736(05)67665-9","article-title":"Guillain-Barr\u00e9 syndrome","volume":"366","author":"RAC Hughes","year":"2005","journal-title":"Lancet"},{"issue":"3","key":"pone.0349687.ref005","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1093\/aje\/kwr072","article-title":"Guillain-Barre syndrome, influenzalike illnesses, and influenza vaccination during seasons with and without circulating A\/H1N1 viruses","volume":"174","author":"L Grimaldi-Bensouda","year":"2011","journal-title":"Am J Epidemiol"},{"issue":"7","key":"pone.0349687.ref006","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00134-010-1895-4","article-title":"Guillain-Barr\u00e9 syndrome related to pandemic influenza A (H1N1) infection","volume":"36","author":"A Chaari","year":"2010","journal-title":"Intensive Care Med"},{"issue":"6","key":"pone.0349687.ref007","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41590-018-0111-5","article-title":"Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza","volume":"19","author":"J Dunning","year":"2018","journal-title":"Nat Immunol"},{"issue":"1","key":"pone.0349687.ref008","article-title":"Identification of gene networks and pathways associated with Guillain-Barr\u00e9 syndrome","volume":"7","author":"K-H Chang","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"pone.0349687.ref009","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"R Edgar","year":"2002","journal-title":"Nucleic Acids Res"},{"issue":"7","key":"pone.0349687.ref010","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref011","unstructured":"Oliveros JC. Venny: An interactive tool for comparing lists with Venn\u2019s diagrams. https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html. 2007. Accessed 2025 December 2."},{"issue":"1","key":"pone.0349687.ref012","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0349687.ref013","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/pro.3715","article-title":"Toward understanding the origin and evolution of cellular organisms","volume":"28","author":"M Kanehisa","year":"2019","journal-title":"Protein Sci"},{"key":"pone.0349687.ref014","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","author":"C-H Chin","year":"2014","journal-title":"BMC Syst Biol"},{"key":"pone.0349687.ref015","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab835","article-title":"The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"D Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref016","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"D Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"issue":"11","key":"pone.0349687.ref017","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":"P Shannon","year":"2003","journal-title":"Genome Res"},{"issue":"6","key":"pone.0349687.ref018","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nprot.2015.052","article-title":"NetworkAnalyst for statistical, visual and network-based meta-analysis of gene expression data","volume":"10","author":"J Xia","year":"2015","journal-title":"Nat Protoc"},{"key":"pone.0349687.ref019","article-title":"miRTarBase update 2018: A resource for experimentally validated microRNA-target interactions","volume":"46","author":"CH Chou","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref020","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkx1141","article-title":"DIANA-TarBase v8: A decade-long collection of experimentally supported miRNA-gene interactions","volume":"46","author":"D Karagkouni","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref021","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab1113","article-title":"JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles","volume":"50","author":"JA Castro-Mondragon","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref022","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw943","article-title":"DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants","volume":"45","author":"J Pi\u00f1ero","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"pone.0349687.ref023","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1093\/bioinformatics\/btv313","article-title":"DSigDB: Drug signatures database for gene set analysis","volume":"31","author":"M Yoo","year":"2015","journal-title":"Bioinformatics"},{"key":"pone.0349687.ref024","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"MV Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0349687.ref025","doi-asserted-by":"crossref","first-page":"798538","DOI":"10.3389\/fimmu.2022.798538","article-title":"Immune response is key to genetic mechanisms of SARS-CoV-2 infection with psychiatric disorders based on differential gene expression pattern analysis","volume":"13","author":"J Xia","year":"2022","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0349687.ref026","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/cei.13279","article-title":"Neuroimmunology\u2014the past, present and future","volume":"197","author":"E Nutma","year":"2019","journal-title":"Clin Exp Immunol"},{"issue":"13","key":"pone.0349687.ref027","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1056\/NEJMra050740","article-title":"Neuraminidase inhibitors for influenza","volume":"353","author":"A Moscona","year":"2005","journal-title":"N Engl J Med"},{"issue":"5","key":"pone.0349687.ref028","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1523\/JNEUROSCI.1650-20.2020","article-title":"The neuroimmunology of chronic pain: From rodents to humans","volume":"41","author":"PM Grace","year":"2021","journal-title":"J Neurosci"},{"issue":"5","key":"pone.0349687.ref029","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.ajhg.2011.10.004","article-title":"Abundant pleiotropy in human complex diseases and traits","volume":"89","author":"S Sivakumaran","year":"2011","journal-title":"Am J Hum Genet"},{"key":"pone.0349687.ref030","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jaut.2016.10.005","article-title":"Impact of tofacitinib treatment on human B-cells in vitro and in vivo","volume":"77","author":"M Rizzi","year":"2017","journal-title":"J Autoimmun"},{"issue":"8","key":"pone.0349687.ref031","article-title":"Kinetic analysis of the influenza A virus HA\/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces","volume":"14","author":"H Guo","year":"2018","journal-title":"PLoS Pathog"},{"key":"pone.0349687.ref032","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0165-5728(93)90255-W","article-title":"Antibody responses to P0 and P2 myelin proteins in Guillain-Barr\u00e9 syndrome and chronic idiopathic demyelinating polyradiculoneuropathy","volume":"46","author":"A Khalili-Shirazi","year":"1993","journal-title":"J Neuroimmunol"},{"issue":"7549","key":"pone.0349687.ref033","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/520609a","article-title":"Personalized medicine: Time for one-person trials","volume":"520","author":"NJ Schork","year":"2015","journal-title":"Nature"},{"issue":"7","key":"pone.0349687.ref034","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1128\/CVI.00010-13","article-title":"Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae","volume":"20","author":"A Tanaka","year":"2013","journal-title":"Clin Vaccine Immunol"},{"issue":"6","key":"pone.0349687.ref035","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1165\/rcmb.2006-0323OC","article-title":"Parthenolide inhibits IkappaB kinase, NF-kappaB activation, and inflammatory response in cystic fibrosis cells and mice","volume":"36","author":"A Saadane","year":"2007","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"10","key":"pone.0349687.ref036","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.4103\/1673-5374.193228","article-title":"Parthenolide: A novel pharmacological approach to promote nerve regeneration","volume":"11","author":"H Diekmann","year":"2016","journal-title":"Neural Regen Res"},{"issue":"7","key":"pone.0349687.ref037","doi-asserted-by":"crossref","first-page":"2546","DOI":"10.1021\/acs.molpharmaceut.0c00244","article-title":"Synthesis of a hexavalent betulinic acid derivative as a hemagglutinin-targeted influenza virus entry inhibitor","volume":"17","author":"Y Chen","year":"2020","journal-title":"Mol Pharm"},{"issue":"6","key":"pone.0349687.ref038","doi-asserted-by":"crossref","first-page":"657","DOI":"10.2174\/0929867053202214","article-title":"Betulinic acid and its derivatives: A review on their biological properties","volume":"12","author":"P Yogeeswari","year":"2005","journal-title":"Curr Med Chem"},{"issue":"5","key":"pone.0349687.ref039","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1208\/s12249-019-1377-0","article-title":"Preformulation and evaluation of tofacitinib as a therapeutic treatment for asthma","volume":"20","author":"US Younis","year":"2019","journal-title":"AAPS PharmSciTech"},{"issue":"7","key":"pone.0349687.ref040","first-page":"7849","article-title":"Myelin ultrastructure of sciatic nerve in rat experimental autoimmune neuritis model and its correlation with associated protein expression","volume":"8","author":"X-J Yuan","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"issue":"1","key":"pone.0349687.ref041","doi-asserted-by":"crossref","DOI":"10.1111\/jns.70012","article-title":"Altered cellular pathways in the blood of patients with Guillain-Barre Syndrome","volume":"30","author":"O Lima","year":"2025","journal-title":"J Peripher Nerv Syst"},{"issue":"4","key":"pone.0349687.ref042","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/ni.3691","article-title":"Mechanisms and consequences of Jak-STAT signaling in the immune system","volume":"18","author":"AV Villarino","year":"2017","journal-title":"Nat Immunol"},{"issue":"1","key":"pone.0349687.ref043","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.autrev.2016.09.022","article-title":"Guillain-Barr\u00e9 syndrome","volume":"16","author":"S Esposito","year":"2017","journal-title":"Autoimmun Rev"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:50:34Z","timestamp":1779299434000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0349687"}},"subtitle":[],"editor":[{"given":"Vijay","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0349687","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}