{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:14Z","timestamp":1787028494071,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005739","name":"Programa de Apoyo a Proyectos de Investigaci\u00f3n e Innovaci\u00f3n Tecnol\u00f3gica (PAPIIT) UNAM","doi-asserted-by":"publisher","award":["IN218019"],"award-info":[{"award-number":["IN218019"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa de Becas Posdoctorales DGAPA-UNAM, M\u00e9xico","award":["IN218019"],"award-info":[{"award-number":["IN218019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Abnormally increased expression of claudin-6 in gastric cancer is considered a prognostic marker of the chromosomal unstable molecular subtype. However, a detailed molecular profile analysis of differentially expressed genes and affected pathways associated with claudin-6 increased (Cldn6high) expression has not been assessed. (2) The TCGA Stomach Adenocarcinoma Pan-Cancer Atlas Data was evaluated using Cytoscape\u2019s Gene Mania, MCODE, and Cytohubba bioinformatic software. (3) 96.88% of Cldn6high gastric cancer tumors belonging to the chromosomal unstable molecular subtype are associated with a worse prognosis. Cldn6expression coincided with higher mutations in TP53, MIEN1, STARD3, PGAP3, and CCNE1 genes compared to Cldn6low expression. In Cldn6high cancers, 1316 genes were highly expressed. Cholesterol metabolism was the most affected pathway as APOA1, APOA2, APOH, APOC2, APOC3, APOB-100, LDL receptor-related protein 1\/2, Sterol O-acyltransferase, STARD3, MAGEA-2, -3, -4, -6, -9B, and -12 genes were overexpressed in Cldn6high gastric cancers; interestingly, APOA2 and MAGEA9b were identified as top hub genes. Functional enrichment of DEGs linked HNF-4\u03b1 and HNF-1\u03b1 genes as highly expressed in Cldn6high gastric cancer. (4) Our results suggest that APOA2 and MAGEA9b could be considered as prognostic markers for Cldn6high gastric cancers.<\/jats:p>","DOI":"10.3390\/ijms232213977","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T02:29:32Z","timestamp":1668392972000},"page":"13977","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Chromosomally Unstable Gastric Cancers Overexpressing Claudin-6 Disclose Cross-Talk between HNF1A and HNF4A, and Upregulated Cholesterol Metabolism"],"prefix":"10.3390","volume":"23","author":[{"given":"Sanyog","family":"Dwivedi","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunobiolog\u00eda, Departamento de Biolog\u00eda Celular y Tisular, Facultad de Medicina, UNAM, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina","family":"Hern\u00e1ndez-Montes","sequence":"additional","affiliation":[{"name":"Red de Apoyo a la Investigaci\u00f3n, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n \u201cDr. Salvador Zubiran\u201d, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Felipe","family":"Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunobiolog\u00eda, Departamento de Biolog\u00eda Celular y Tisular, Facultad de Medicina, UNAM, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Patricia","family":"Rend\u00f3n-Huerta","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunobiolog\u00eda, Departamento de Biolog\u00eda Celular y Tisular, Facultad de Medicina, UNAM, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1158\/1541-7786.MCR-17-0070","article-title":"Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution","volume":"15","author":"Gupta","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513, 202\u2013209.","DOI":"10.1038\/nature13480"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1038\/ncomms2992","article-title":"Immunologic and chemical targeting of the tight-junction protein Claudin-6 eliminates tumorigenic human pluripotent stem cells","volume":"4","author":"Nudel","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1091555","DOI":"10.1080\/2162402X.2015.1091555","article-title":"Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6","volume":"5","author":"Stadler","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s12029-009-9110-y","article-title":"Distribution and expression pattern of claudins 6, 7, and 9 in diffuse- and intestinal-type gastric adenocarcinomas","volume":"41","author":"Teresa","year":"2010","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"688","DOI":"10.5306\/wjco.v12.i8.688","article-title":"Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery","volume":"12","author":"Ramos","year":"2021","journal-title":"World J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nm.3850","article-title":"Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes","volume":"21","author":"Cristescu","year":"2015","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/07357907.2010.512594","article-title":"Claudin-6, 7, or 9 overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate","volume":"29","author":"Fortoul","year":"2011","journal-title":"Cancer Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/s41419-019-2168-y","article-title":"CLDN6 promotes tumor progression through the YAP1-snail1 axis in gastric cancer","volume":"10","author":"Yu","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"329","DOI":"10.3233\/CBM-201554","article-title":"Claudin-6 is down-regulated in gastric cancer and its potential pathway","volume":"28","author":"Lu","year":"2020","journal-title":"Cancer Biomark."},{"key":"ref_12","first-page":"4621","article-title":"Expression of CLDN6 in tissues of gastric cancer patients: Association with clinical pathology and prognosis","volume":"17","author":"Gao","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/ncponc1187","article-title":"Strategies for discovering novel cancer biomarkers through utilization of emerging technologies","volume":"5","author":"Kulasingam","year":"2008","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70271","DOI":"10.18632\/oncotarget.20082","article-title":"Identification of core genes and outcome in gastric cancer using bioinformatics analysis","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.yexmp.2014.02.007","article-title":"Gene expression profiling and bioinformatics analysis of gastric carcinoma","volume":"96","author":"Liu","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s10120-021-01201-9","article-title":"A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics","volume":"24","author":"Wang","year":"2021","journal-title":"Gastric Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/humu.10180","article-title":"TP53 and gastric carcinoma: A review","volume":"21","author":"Wang","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12967-019-1941-0","article-title":"Mutational landscape of gastric cancer and clinical application of genomic profiling based on target next-generation sequencing","volume":"17","author":"Cai","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1053\/j.gastro.2009.05.001","article-title":"Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location","volume":"137","author":"Murphy","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13073-021-00963-2","article-title":"The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma","volume":"13","author":"Chen","year":"2021","journal-title":"Genome Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jprot.2018.07.013","article-title":"Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer","volume":"186","author":"Gil","year":"2018","journal-title":"J. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ccell.2018.12.003","article-title":"Proteogenomic Characterization of Human Early-Onset Gastric Cancer","volume":"35","author":"Mun","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1749-6632.2000.tb05235.x","article-title":"The structure and function of claudins, cell adhesion molecules at tight junctions","volume":"915","author":"Tsukita","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190278","DOI":"10.1098\/rsob.190278","article-title":"The multifarious regulation of the apical junctional complex","volume":"10","author":"Rusu","year":"2020","journal-title":"Open Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Qu, H., Jin, Q., and Quan, C. (2021). CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413416"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.yexcr.2016.11.025","article-title":"Claudin-6 enhances cell invasiveness through claudin-1 in AGS human adenocarcinoma gastric cancer cells","volume":"350","author":"Montano","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ccr.2007.10.001","article-title":"Shaping genetic alterations in human cancer: The p53 mutation paradigm","volume":"12","author":"Soussi","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_30","first-page":"5800","article-title":"p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases","volume":"51","author":"Yamada","year":"1991","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41598-020-57544-3","article-title":"Clinical relevance of somatic mutations in main driver genes detected in gastric cancer patients by next-generation DNA sequencing","volume":"10","author":"Nemtsova","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Blanchet, A., Bourgmayer, A., Kurtz, J.E., Mellitzer, G., and Gaiddon, C. (2021). Isoforms of the p53 Family and Gastric Cancer: A Menage a Trois for an Unfinished Affair. Cancers, 13.","DOI":"10.3390\/cancers13040916"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"868","DOI":"10.3389\/fonc.2019.00868","article-title":"Emerging Role of Migration and Invasion Enhancer 1 (MIEN1) in Cancer Progression and Metastasis","volume":"9","author":"Kushwaha","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.ajpath.2014.12.018","article-title":"Elevated levels of StAR-related lipid transfer protein 3 alter cholesterol balance and adhesiveness of breast cancer cells: Potential mechanisms contributing to progression of HER2-positive breast cancers","volume":"185","author":"Vassilev","year":"2015","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.2147\/OTT.S233672","article-title":"Biological Roles and Mechanisms of Circular RNA in Human Cancers","volume":"13","author":"Tang","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"92209","DOI":"10.18632\/oncotarget.21150","article-title":"Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer","volume":"8","author":"Kwon","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s13148-018-0550-8","article-title":"Epigenetic regulation of MAGE family in human cancer progression-DNA methylation, histone modification, and non-coding RNAs","volume":"10","author":"Lian","year":"2018","journal-title":"Clin. Epigenet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1245\/s10434-010-1399-z","article-title":"Clinical significance of melanoma antigen-encoding gene-1 (MAGE-1) expression and its correlation with poor prognosis in differentiated advanced gastric cancer","volume":"18","author":"Ogata","year":"2011","journal-title":"Ann. Surg. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.18632\/oncotarget.6741","article-title":"High expression levels of MAGE-A9 are correlated with unfavorable survival in lung adenocarcinoma","volume":"7","author":"Zhai","year":"2016","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3109\/00365599.2012.740070","article-title":"Prognostic value of melanoma-associated antigen A9 in renal cell carcinoma","volume":"47","author":"Hatiboglu","year":"2013","journal-title":"Scand. J. Urol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1158\/1078-0432.CCR-04-0468","article-title":"Melanoma-associated antigens in esophageal adenocarcinoma: Identification of novel MAGE-A10 splice variants","volume":"10","author":"Lin","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_42","first-page":"541","article-title":"High expression of MAGE-A9 in tumor and stromal cells of non-small cell lung cancer was correlated with patient poor survival","volume":"8","author":"Zhang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_43","first-page":"1529","article-title":"Expression of the TRAG-3 gene in human esophageal cancer: The frequent synchronous expression of MAGE-3 gene","volume":"15","author":"Ohta","year":"2006","journal-title":"Oncol. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1002\/1097-0142(20010515)91:10<1882::AID-CNCR1210>3.0.CO;2-H","article-title":"MAGE, BAGE, and GAGE gene expression in patients with esophageal squamous cell carcinoma and adenocarcinoma of the gastric cardia","volume":"91","author":"Zambon","year":"2001","journal-title":"Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"632219","DOI":"10.3389\/fmolb.2021.632219","article-title":"IGF2BP1, a Conserved Regulator of RNA Turnover in Cancer","volume":"8","author":"Glass","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1126\/science.aay5967","article-title":"An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors","volume":"367","author":"Reinhard","year":"2020","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3892\/mmr.2021.12316","article-title":"Claudin 6: Therapeutic prospects for tumours, and mechanisms of expression and regulation (Review)","volume":"24","author":"Du","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1093\/carcin\/bgg129","article-title":"Identification of genes preferentially expressed in mammary epithelial cells of Copenhagen rat using subtractive hybridization and microarrays","volume":"24","author":"Quan","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1186\/s13046-019-1359-9","article-title":"Estrogen receptor beta inhibits breast cancer cells migration and invasion through CLDN6-mediated autophagy","volume":"38","author":"Song","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0079-6107(03)00028-2","article-title":"On the structure and function of apolipoproteins: More than a family of lipid-binding proteins","volume":"83","author":"Miguel","year":"2003","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1111\/j.1742-4658.2012.08644.x","article-title":"Lipid metabolism in cancer","volume":"279","author":"Santos","year":"2012","journal-title":"FEBS J."},{"key":"ref_52","first-page":"778","article-title":"Lipid metabolism and carcinogenesis, cancer development","volume":"8","author":"Long","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1124\/dmd.115.068254","article-title":"Kidney versus Liver Specification of SLC and ABC Drug Transporters, Tight Junction Molecules, and Biomarkers","volume":"44","author":"Martovetsky","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s12276-020-00551-1","article-title":"Hepatocyte nuclear factor 4alpha and cancer-related cell signaling pathways: A promising insight into cancer treatment","volume":"53","author":"Lv","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/gutjnl-2018-318025","article-title":"HNF4alpha pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer","volume":"69","author":"Xu","year":"2020","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.molcel.2019.09.008","article-title":"Even Cancer Cells Watch Their Cholesterol!","volume":"76","author":"Riscal","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kahn, B.M., Lucas, A., Alur, R.G., Wengyn, M.D., Schwartz, G.W., Li, J., Sun, K., Maurer, H.C., Olive, K.P., and Faryabi, R.B. (2021). The vascular landscape of human cancer. J. Clin. Investig., 131.","DOI":"10.1172\/JCI136655"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1002\/pmic.201400515","article-title":"FunRich: An open access standalone functional enrichment and interaction network analysis tool","volume":"15","author":"Pathan","year":"2015","journal-title":"Proteomics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W214","DOI":"10.1093\/nar\/gkq537","article-title":"The GeneMANIA prediction server: Biological network integration for gene prioritization and predicting gene function","volume":"38","author":"Donaldson","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_63","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."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-2"},{"key":"ref_65","doi-asserted-by":"crossref","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":"ref_66","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/ng1844","article-title":"Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways","volume":"38","author":"Lehner","year":"2006","journal-title":"Nat. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/13977\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:17:07Z","timestamp":1760145427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/13977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,12]]},"references-count":66,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232213977"],"URL":"https:\/\/doi.org\/10.3390\/ijms232213977","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,12]]}}}