{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:27:34Z","timestamp":1792445254673,"version":"4.5.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> As the most prevalent valvular heart disease, calcific aortic valve disease (CAVD) has become a primary cause of aortic valve stenosis and insufficiency. We aim to illustrate the roles of immune related genes (IRGs) and immune cells infiltration in the occurrence of CAVD.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Integrative meta-analysis of expression data (INMEX) was adopted to incorporate multiple gene expression datasets of CAVD from Gene Expression Omnibus (GEO) database. By matching the differentially expressed genes (DEGs) to IRGs from \u201cImmPort\u201d database, differentially expressed immune related genes (DEIRGs) were screened out. We performed enrichment analysis and found that DEIRGs in CAVD were closely related to inflammatory response and immune cells infiltration. We also constructed protein\u2013protein interaction (PPI) network of DEIRGs and identified 5 key DEIRGs in CAVD according to the mixed character calculation results. Moreover, CIBERSORT algorithm was used to explore the profile of infiltrating immune cells in CAVD. Based on Spearman\u2019s rank correlation method, correlation analysis between key DEIRGs and infiltrating immune cells was performed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 220 DEIRGs were identified and the enrichment analysis of DEIRGs showed that they were significantly enriched in inflammatory responses. PPI network was constructed and <jats:italic>PTPN11<\/jats:italic>, <jats:italic>GRB2<\/jats:italic>, <jats:italic>SYK<\/jats:italic>, <jats:italic>PTPN6<\/jats:italic> and <jats:italic>SHC1<\/jats:italic> were identified as key DEIRGs. Compared with normal aortic valve tissue samples, the proportion of neutrophils, T cells CD4 memory activated and macrophages M0 was elevated in calcified aortic valves tissue samples, as well as reduced infiltration of macrophages M2 and NK cells activated. Furthermore, key DEIRGs identified in the present study, including <jats:italic>PTPN11<\/jats:italic>, <jats:italic>GRB2<\/jats:italic>, <jats:italic>PTPN6<\/jats:italic>, <jats:italic>SYK<\/jats:italic>, and <jats:italic>SHC1<\/jats:italic>, were all significantly correlated with infiltration of various immune cells.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This meta-analysis suggested that <jats:italic>PTPN11<\/jats:italic>, <jats:italic>GRB2<\/jats:italic>, <jats:italic>PTPN6<\/jats:italic>, <jats:italic>SYK<\/jats:italic>, and <jats:italic>SHC1<\/jats:italic> might be key DEIRGs associated with immune cells infiltration, which play a pivotal role in pathogenesis of CAVD.<\/jats:p>","DOI":"10.3389\/fgene.2022.971808","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T04:59:40Z","timestamp":1663736380000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Integrated identification of key immune related genes and patterns of immune infiltration in calcified aortic valvular disease: A network based meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Li-Da","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Ling","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Xing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.biopsych.2010.09.022","article-title":"Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology","volume":"68","author":"Abazyan","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1159\/000489863","article-title":"Spleen tyrosine kinase as a target therapy for pseudomonas aeruginosa infection","volume":"10","author":"Alhazmi","year":"2018","journal-title":"J. Innate Immun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"103380","DOI":"10.1016\/j.jbi.2020.103380","article-title":"Systematic comparison of the protein-protein interaction databases from a user's perspective","volume":"103","author":"Bajpai","year":"2020","journal-title":"J. Biomed. Inf."},{"key":"B4","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2013update","volume":"41","author":"Barrett","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1093\/cvr\/cvab273","article-title":"Innate and adaptative immunity: The understudied driving force of heart valve disease","volume":"117","author":"Bartoli-Leonard","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1161\/CIRCRESAHA.120.317979","article-title":"Multi-omics approaches to define calcific aortic valve disease pathogenesis","volume":"128","author":"Blaser","year":"2021","journal-title":"Circ. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1161\/CIRCGENETICS.108.820795","article-title":"Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves","volume":"2","author":"Boss\u00e9","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1089\/gtmb.2009.0192","article-title":"PTPN11 and KRAS gene analysis in patients with Noonan and Noonan-like syndromes","volume":"14","author":"Brasil","year":"2010","journal-title":"Genet. Test. Mol. Biomarkers"},{"key":"B9","doi-asserted-by":"publisher","first-page":"660797","DOI":"10.3389\/fcvm.2021.660797","article-title":"Dissecting calcific aortic valve disease-the role, etiology, and drivers of valvular fibrosis","volume":"8","author":"B\u00fcttner","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/73528","article-title":"Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis","volume":"24","author":"Chen","year":"2000","journal-title":"Nat. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","article-title":"cytoHubba: identifying hub objects and sub-networks from complex interactome","volume":"8","author":"Chin","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.atherosclerosis.2018.08.029","article-title":"Inflammatory and metabolic mechanisms underlying the calcific aortic valve disease","volume":"277","author":"Cho","year":"2018","journal-title":"Atherosclerosis"},{"key":"B13","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.gene.2006.01.023","article-title":"Molecular regulation of receptor tyrosine kinases in hematopoietic malignancies","volume":"374","author":"Correll","year":"2006","journal-title":"Gene"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the gene expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3390\/diagnostics10030171","article-title":"GRB10 and E2F3 as diagnostic markers of osteoarthritis and their correlation with immune infiltration","volume":"10","author":"Deng","year":"2020","journal-title":"Diagn. (Basel)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1097\/01.cad.0000185180.72604.ac","article-title":"Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy","volume":"17","author":"Dharmawardana","year":"2006","journal-title":"Anticancer. Drugs"},{"key":"B17","doi-asserted-by":"publisher","first-page":"639642","DOI":"10.3389\/fgene.2021.639642","article-title":"Immune-related genes are prognostic markers for prostate cancer recurrence","volume":"12","author":"Fu","year":"2021","journal-title":"Front. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1152\/physiolgenomics.00041.2016","article-title":"RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing","volume":"48","author":"Guauque-Olarte","year":"2016","journal-title":"Physiol. Genomics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","article-title":"TRRUST v2: An expanded reference database of human and mouse transcriptional regulatory interactions","volume":"46","author":"Han","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1631","DOI":"10.4049\/jimmunol.1200551","article-title":"Deficiency in hematopoietic phosphatase ptpn6\/Shp1 hyperactivates the innate immune system and impairs control of bacterial infections in zebrafish embryos","volume":"190","author":"Kanwal","year":"2013","journal-title":"J. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/s0952-7915(00)00087-x","article-title":"Functional dissection of BCR signaling pathways","volume":"12","author":"Kurosaki","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/ni.2789","article-title":"Molecular signatures of antibody responses derived from a systems biology study of five human vaccines","volume":"15","author":"Li","year":"2014","journal-title":"Nat. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.12659\/MSM.913543","article-title":"The expression and clinical significance of spleen tyrosine kinase in patients with coronary heart disease","volume":"25","author":"Liang","year":"2019","journal-title":"Med. Sci. Monit."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1002\/1873-3468.13879","article-title":"SHP-1 ameliorates nonalcoholic steatohepatitis by inhibiting proinflammatory cytokine production","volume":"594","author":"Lin","year":"2020","journal-title":"FEBS Lett."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8846951","DOI":"10.1155\/2021\/8846951","article-title":"Construction of potential gene expression and regulation networks in prostate cancer using bioinformatics tools","volume":"2021","author":"Liu","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jacbts.2019.10.004","article-title":"Celastrol alleviates aortic valve calcification via inhibition of NADPH oxidase 2 in valvular interstitial cells","volume":"5","author":"Liu","year":"2019","journal-title":"JACC. Basic Transl. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"102602","DOI":"10.1016\/j.ebiom.2019.102602","article-title":"Tumour immune cell infiltration and survival after platinum-based chemotherapy in high-grade serous ovarian cancer subtypes: A gene expression-based computational study","volume":"51","author":"Liu","year":"2020","journal-title":"EBioMedicine"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2009.09.026","article-title":"Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis","volume":"48","author":"Liu","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.pbiomolbio.2016.02.002","article-title":"Osteogenesis in calcified aortic valve disease: From histopathological observation towards molecular understanding","volume":"122","author":"Liu","year":"2016","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1007\/s00380-014-0497-4","article-title":"The expression of p66shc in peripheral blood monocytes is increased in patients with coronary heart disease and correlated with endothelium-dependent vasodilatation","volume":"30","author":"Miao","year":"2015","journal-title":"Heart Vessels"},{"key":"B31","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/nri2765","article-title":"The SYK tyrosine kinase: A crucial player in diverse biological functions","volume":"10","author":"Mocsai","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.phrs.2018.08.020","article-title":"Novel pharmacological targets for calcific aortic valve disease: Prevention and treatments","volume":"136","author":"Myasoedova","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat. Methods"},{"key":"B35","doi-asserted-by":"publisher","first-page":"423","DOI":"10.3109\/07853890.2015.1059955","article-title":"MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic valve disease","volume":"47","author":"Ohukainen","year":"2015","journal-title":"Ann. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1056\/NEJMra1313875","article-title":"Aortic-valve stenosis-from patients at risk to severe valve obstruction","volume":"371","author":"Otto","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"D833","DOI":"10.1093\/nar\/gkw943","article-title":"DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants","volume":"45","author":"Pinero","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"R66","DOI":"10.1093\/hmg\/ddt347","article-title":"PTPs emerge as PIPs: Protein tyrosine phosphatases with lipid-phosphatase activities in human disease","volume":"22","author":"Pulido","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"145987","DOI":"10.1016\/j.gene.2021.145987","article-title":"Exploring potential genes and pathways related to calcific aortic valve disease","volume":"808","author":"Qiao","year":"2022","journal-title":"Gene"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.4049\/jimmunol.1501764","article-title":"Grb2 is important for T cell development, Th cell differentiation, and induction of experimental autoimmune encephalomyelitis","volume":"196","author":"Radtke","year":"2016","journal-title":"J. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3515001","DOI":"10.1155\/2022\/3515001","article-title":"Combination of enrichment using gene ontology and transcriptomic analysis revealed contribution of interferon signaling to severity of COVID-19","volume":"2022","author":"Ramadhani","year":"2022","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"H231","DOI":"10.1152\/ajpheart.00665.2011","article-title":"The PTPN11 loss-of-function mutation Q510E-Shp2 causes hypertrophic cardiomyopathy by dysregulating mTOR signaling","volume":"302","author":"Schramm","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B44","doi-asserted-by":"publisher","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."},{"key":"B45","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.jare.2020.07.005","article-title":"Hydrogen sulfide inhibits aortic valve calcification in heart via regulating RUNX2 by NF-\u03baB, a link between inflammation and mineralization","volume":"27","author":"Sikura","year":"2020","journal-title":"J. Adv. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1536\/ihj.18-196","article-title":"Predictive roles of neutrophil-to-lymphocyte ratio and c-reactive protein in patients with calcific aortic valve disease","volume":"60","author":"Song","year":"2019","journal-title":"Int. Heart J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1097\/MIB.0000000000000297","article-title":"Role of protein tyrosine phosphatases in regulating the immune system: Implications for chronic intestinal inflammation","volume":"21","author":"Spalinger","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/s41590-019-0550-7","article-title":"Ptpn6 inhibits caspase-8- and Ripk3\/Mlkl-dependent inflammation","volume":"21","author":"Speir","year":"2020","journal-title":"Nat. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.prp.2012.02.009","article-title":"Calcific aortic valve stenosis: Immunohistochemical analysis of inflammatory infiltrate","volume":"208","author":"Steiner","year":"2012","journal-title":"Pathol. Res. Pract."},{"key":"B50","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12920-021-00989-w","article-title":"Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis","volume":"14","author":"Sun","year":"2021","journal-title":"BMC Med. Genomics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/s0093-7754(01)90291-x","article-title":"GRB2: A pivotal protein in signal transduction","volume":"28","author":"Tari","year":"2001","journal-title":"Semin. Oncol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e21286","DOI":"10.1097\/MD.0000000000021286","article-title":"Identification of key genes in calcific aortic valve disease by integrated bioinformatics analysis","volume":"99","author":"Teng","year":"2020","journal-title":"Medicine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1074\/jbc.M109.017491","article-title":"Decreased superoxide production in macrophages of long-lived p66Shc knock-out mice","volume":"285","author":"Tomilov","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B55","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.imbio.2012.01.001","article-title":"Regulation of SHP2 by PTEN\/AKT\/GSK-3\u03b2 signaling facilitates IFN-\u03b3 resistance in hyperproliferating gastric cancer","volume":"217","author":"Tseng","year":"2012","journal-title":"Immunobiology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.jacc.2017.11.014","article-title":"NHLBI working group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis","volume":"71","author":"Tsimikas","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1093\/ejcts\/ezs455","article-title":"Guidelines on the management of valvular heart disease (version 2012): The joint task force on the management of valvular heart disease of the European society of cardiology (ESC) and the European association for cardio-thoracic surgery (EACTS)","volume":"42","author":"Vahanian","year":"2012","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e27508","DOI":"10.1097\/MD.0000000000027508","article-title":"Comparison of critical biomarkers in 2 erectile dysfunction models based on GEO and NOS-cGMP-PDE5 pathway","volume":"100","author":"Wang","year":"2021","journal-title":"Med. Baltim."},{"key":"B59","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation."},{"key":"B60","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1093\/nar\/gkt338","article-title":"INMEX-a web-based tool for integrative meta-analysis of expression data","volume":"41","author":"Xia","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1084\/jem.20181198","article-title":"Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10","volume":"216","author":"Xiao","year":"2019","journal-title":"J. Exp. Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3822","DOI":"10.1016\/j.sjbs.2022.03.007","article-title":"Gene and protein interaction network analysis in the epithelial-mesenchymal transition of Hertwig's Epithelial Root Sheath reveals periodontal regenerative drug targets - an in silico study","volume":"29","author":"Yadalam","year":"2022","journal-title":"Saudi J. Biol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"730","DOI":"10.21037\/atm.2019.11.117","article-title":"Exploration of the immune-related signature and immune infiltration analysis for breast ductal and lobular carcinoma","volume":"7","author":"Zhang","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s12929-018-0459-8","article-title":"Identification of target genes in cardiomyopathy with fibrosis and cardiac remodeling","volume":"25","author":"Zhao","year":"2018","journal-title":"J. Biomed. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1093\/infdis\/jiw205","article-title":"Shp2 deficiency impairs the inflammatory response against haemophilus influenzae by regulating macrophage polarization","volume":"214","author":"Zhao","year":"2016","journal-title":"J. Infect. Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s00109-020-01896-w","article-title":"Leukocyte immunoglobulin-like receptor B4 protects against cardiac hypertrophy via SHP-2-dependent inhibition of the NF-\u03baB pathway","volume":"98","author":"Zhou","year":"2020","journal-title":"J. Mol. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3389\/fcell.2020.00056","article-title":"Interleukin 37 suppresses M1 macrophage polarization through inhibition of the Notch1 and nuclear factor kappa B pathways","volume":"8","author":"Zhou","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.971808\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T04:59:44Z","timestamp":1663736384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.971808\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":68,"alternative-id":["10.3389\/fgene.2022.971808"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.971808","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]},"article-number":"971808"}}