{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:10:59Z","timestamp":1766869859938,"version":"build-2065373602"},"reference-count":66,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T00:00:00Z","timestamp":1560816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["V0.25011\/542-HRD\/2016-HR"],"award-info":[{"award-number":["V0.25011\/542-HRD\/2016-HR"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01AT003961","R01AT006888","R01AI123947","R01AI129788","R01MH094755","P20GM103641"],"award-info":[{"award-number":["P01AT003961","R01AT006888","R01AI123947","R01AI129788","R01MH094755","P20GM103641"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer is a leading cancer type and one of the major health issues faced by women around the world. Some of its major risk factors include body mass index, hormone replacement therapy, family history and germline mutations. Of these risk factors, estrogen levels play a crucial role. Among the estrogen receptors, estrogen receptor alpha (ER\u03b1) is known to interact with tumor suppressor protein p53 directly thereby repressing its function. Previously, we have studied the impact of deleterious breast cancer-associated non-synonymous single nucleotide polymorphisms (nsnps) rs11540654 (R110P), rs17849781 (P278A) and rs28934874 (P151T) in TP53 gene on the p53 DNA-binding core domain. In the present study, we aimed to analyze the impact of these mutations on p53\u2013ER\u03b1 interaction. To this end, we, have modelled the full-length structure of human p53 and validated its quality using PROCHECK and subjected it to energy minimization using NOMAD-Ref web server. Three-dimensional structure of ER\u03b1 activation function-2 (AF-2) domain was downloaded from the protein data bank. Interactions between the modelled native and mutant (R110P, P278A, P151T) p53 with ER\u03b1 was studied using ZDOCK. Machine learning predictions on the interactions were performed using Weka software. Results from the protein\u2013protein docking showed that the atoms, residues and solvent accessibility surface area (SASA) at the interface was increased in both p53 and ER\u03b1 for R110P mutation compared to the native complexes indicating that the mutation R110P has more impact on the p53\u2013ER\u03b1 interaction compared to the other two mutants. Mutations P151T and P278A, on the other hand, showed a large deviation from the native p53-ER\u03b1 complex in atoms and residues at the surface. Further, results from artificial neural network analysis showed that these structural features are important for predicting the impact of these three mutations on p53\u2013ER\u03b1 interaction. Overall, these three mutations showed a large deviation in total SASA in both p53 and ER\u03b1. In conclusion, results from our study will be crucial in making the decisions for hormone-based therapies against breast cancer.<\/jats:p>","DOI":"10.3390\/ijms20122962","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T02:42:46Z","timestamp":1560912166000},"page":"2962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Analysis of the TP53 Deleterious Single Nucleotide Polymorphisms Impact on Estrogen Receptor Alpha-p53 Interaction: A Machine Learning Approach"],"prefix":"10.3390","volume":"20","author":[{"given":"Kumaraswamy Naidu","family":"Chitrala","sequence":"first","affiliation":[{"name":"Department of Zoology, Sri Venkateswara University, Tirupati 517502, India"},{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitzi","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prakash","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suneetha","family":"Yeguvapalli","sequence":"additional","affiliation":[{"name":"Department of Zoology, Sri Venkateswara University, Tirupati 517502, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3816\/CBC.2005.n.043","article-title":"The global breast cancer burden: Variations in epidemiology and survival","volume":"6","author":"Hortobagyi","year":"2005","journal-title":"Clin. Breast Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMp0708307","article-title":"\u201cWesternizing\u201d women\u2019s risks? Breast cancer in lower-income countries","volume":"358","author":"Porter","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1007\/s00268-007-9454-z","article-title":"Breast cancer issues in developing countries: An overview of the Breast Health Global Initiative","volume":"32","author":"Anderson","year":"2008","journal-title":"World J. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1111\/j.1743-7563.2008.00191.x","article-title":"Epidemiology, screening and diagnosis of breast cancer in the Asia\u2013Pacific region: Current perspectives and important considerations","volume":"4","author":"Green","year":"2008","journal-title":"Asia\u2013Pac. J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1159\/000115288","article-title":"Breast Cancer Care in India: The Current Scenario and the Challenges for the Future","volume":"3","author":"Agarwal","year":"2008","journal-title":"Breast Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1097\/01.SLA.0000059969.64262.87","article-title":"Rating the risk factors for breast cancer","volume":"237","author":"Singletary","year":"2003","journal-title":"Ann. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1210\/me.2010-0252","article-title":"Estrogen receptor-alpha promotes breast cancer cell motility and invasion via focal adhesion kinase and N-WASP","volume":"24","author":"Sanchez","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1016\/j.chemosphere.2013.01.112","article-title":"Microbial degradation of steroidal estrogens","volume":"91","author":"Yu","year":"2013","journal-title":"Chemosphere"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2147\/IJWH.S41897","article-title":"Improved compliance and patient satisfaction with estradiol vaginal tablets in postmenopausal women previously treated with another local estrogen therapy","volume":"5","author":"Minkin","year":"2013","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.critrevonc.2004.02.001","article-title":"Estrogens and their receptors in breast cancer progression: A dual role in cancer proliferation and invasion","volume":"51","author":"Platet","year":"2004","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0039-128X(00)00143-4","article-title":"Estrogen receptor antibodies: Specificity and utility in detection, localization and analyses of estrogen receptor alpha and beta","volume":"66","author":"Pavao","year":"2001","journal-title":"Steroids"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1631\/jzus.B1300264","article-title":"Harnessing the immune system for the treatment of breast cancer","volume":"15","author":"Jiang","year":"2014","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18060","DOI":"10.1073\/pnas.1018858109","article-title":"Estrogen receptor prevents p53-dependent apoptosis in breast cancer","volume":"109","author":"Bailey","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1101\/gad.552910","article-title":"Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer","volume":"24","author":"Stark","year":"2010","journal-title":"Genes Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9837","DOI":"10.1074\/jbc.C600001200","article-title":"Estrogen receptor-alpha binds p53 tumor suppressor protein directly and represses its function","volume":"281","author":"Liu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"30117","DOI":"10.1074\/jbc.M112.367326","article-title":"p53, a target of estrogen receptor (ER) alpha, modulates DNA damage-induced growth suppression in ER-positive breast cancer cells","volume":"287","author":"Berger","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15081","DOI":"10.1073\/pnas.1009575107","article-title":"Mechanisms of estrogen receptor antagonism toward p53 and its implications in breast cancer therapeutic response and stem cell regulation","volume":"107","author":"Konduri","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10549-008-0044-z","article-title":"Disruption of estrogen receptor alpha-p53 interaction in breast tumors: A novel mechanism underlying the anti-tumor effect of radiation therapy","volume":"115","author":"Liu","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14898","DOI":"10.3390\/ijms131114898","article-title":"A DNA Repair BRCA1 Estrogen Receptor and Targeted Therapy in Breast Cancer","volume":"13","author":"Ratanaphan","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chitrala, K.N., and Yeguvapalli, S. (2014). Computational screening and molecular dynamic simulation of breast cancer associated deleterious non-synonymous single nucleotide polymorphisms in TP53 gene. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104242"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/323533a0","article-title":"Learning representations by back-propagating errors","volume":"323","author":"Rumelhart","year":"1986","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.2174\/156802608786141160","article-title":"Molecular architecture of tumor suppressor p53","volume":"8","author":"Viadiu","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"D115","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: The Universal Protein knowledgebase","volume":"32","author":"Apweiler","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W52","DOI":"10.1093\/nar\/gkl082","article-title":"NOMAD-Ref: Visualization, deformation and refinement of macromolecular structures based on all-atom normal mode analysis","volume":"34","author":"Lindahl","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1016\/j.bmcl.2007.01.054","article-title":"Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha","volume":"17","author":"Dykstra","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1002\/prot.10389","article-title":"ZDOCK: An initial-stage protein-docking algorithm","volume":"52","author":"Chen","year":"2003","journal-title":"Proteins"},{"key":"ref_27","unstructured":"(2006). PyMol, DeLano Scientific. version 0.99."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jmb.2007.05.022","article-title":"Inference of macromolecular assemblies from crystalline state","volume":"372","author":"Krissinel","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1136\/amiajnl-2012-001332","article-title":"Machine learning for predicting the response of breast cancer to neoadjuvant chemotherapy","volume":"20","author":"Mani","year":"2013","journal-title":"J. Am. Med. Inform. Assoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"240673","DOI":"10.1155\/2014\/240673","article-title":"Prediction of protein-protein interaction strength using domain features with supervised regression","volume":"2014","author":"Kamada","year":"2014","journal-title":"Sci. World J."},{"key":"ref_31","first-page":"513","article-title":"Ballet as a movement-based contemplative practice? Implications for neuroscientific studies","volume":"8","year":"2014","journal-title":"Front. Hum. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2478\/s11658-011-0008-x","article-title":"PPI_SVM: Prediction of protein-protein interactions using machine learning, domain-domain affinities and frequency tables","volume":"16","author":"Chatterjee","year":"2011","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hall, M., Frank, E., Holmes, G., Pfahringer, B., Reutemann, P., and Witten, I.H. (2009). The WEKA Data Mining Software: An Update. Sigkdd Explor., 11.","DOI":"10.1145\/1656274.1656278"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"152","DOI":"10.2174\/1871520616666160502122724","article-title":"Breast Cancer: Current Molecular Therapeutic Targets and New Players","volume":"17","author":"Nagini","year":"2017","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mahdavi, M., Nassiri, M., Kooshyar, M.M., Vakili-Azghandi, M., Avan, A., Sandry, R., Pillai, S., Lam, A.K., and Gopalan, V. (2018). Hereditary breast cancer; Genetic penetrance and current status with BRCA. J. Cell. Physiol.","DOI":"10.1002\/jcp.27464"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/annonc\/mdv022","article-title":"Genetics of breast cancer: A topic in evolution","volume":"26","author":"Shiovitz","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.breast.2013.07.005","article-title":"p53 in breast cancer subtypes and new insights into response to chemotherapy","volume":"22","author":"Bertheau","year":"2013","journal-title":"Breast"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nchembio.546","article-title":"Gain of function of mutant p53 by coaggregation with multiple tumor suppressors","volume":"7","author":"Xu","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/cdd.2013.132","article-title":"Mapping the p53 transcriptome universe using p53 natural polymorphs","volume":"21","author":"Wang","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10549-008-0052-z","article-title":"Mutation analysis of BRIP1\/BACH1 in BRCA1\/BRCA2 negative Chinese women with early onset breast cancer or affected relatives","volume":"115","author":"Cao","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/gim.2014.176","article-title":"Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1\/2-negative patients with early-onset breast cancer","volume":"17","author":"Maxwell","year":"2015","journal-title":"Genet. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.cell.2017.08.028","article-title":"Putting p53 in Context","volume":"170","author":"Kastenhuber","year":"2017","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/protein\/gzq074","article-title":"The relevance of protein-protein interactions for p53 function: The CPE contribution","volume":"24","author":"Sot","year":"2011","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1242\/jcs.064501","article-title":"p53 at a glance","volume":"123","author":"Brady","year":"2010","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7746","DOI":"10.1158\/0008-5472.CAN-06-3724","article-title":"Estrogen receptor alpha inhibits p53-mediated transcriptional repression: Implications for the regulation of apoptosis","volume":"67","author":"Sayeed","year":"2007","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"a000919","DOI":"10.1101\/cshperspect.a000919","article-title":"The tumor suppressor p53: From structures to drug discovery","volume":"2","author":"Joerger","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"44330","DOI":"10.1074\/jbc.M112.417980","article-title":"Evaluating Drosophila p53 as a model system for studying cancer mutations","volume":"287","author":"Herzog","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pagano, B., Jama, A., Martinez, P., Akanho, E., Bui, T.T., Drake, A.F., Fraternali, F., and Nikolova, P.V. (2013). Structure and stability insights into tumour suppressor p53 evolutionary related proteins. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076014"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.celrep.2017.11.112","article-title":"Monoclonal Antibodies against Specific p53 Hotspot Mutants as Potential Tools for Precision Medicine","volume":"22","author":"Hwang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/978-1-4939-7000-1_26","article-title":"Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive","volume":"1607","author":"Burley","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1158\/0008-5472.CAN-10-1899","article-title":"The role of calcium in the activation of estrogen receptor-alpha","volume":"71","author":"Divekar","year":"2011","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.addr.2010.08.001","article-title":"Selectively targeting estrogen receptors for cancer treatment","volume":"62","author":"Shanle","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.yexmp.2009.12.003","article-title":"Protein and gene expression of estrogen receptor alpha and nuclear morphology of two breast cancer cell lines after different fixation methods","volume":"88","author":"Nykanen","year":"2010","journal-title":"Exp. Mol. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s12035-012-8377-3","article-title":"Brain endogenous estrogen levels determine responses to estrogen replacement therapy via regulation of BACE1 and NEP in female Alzheimer\u2019s transgenic mice","volume":"47","author":"Li","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_55","first-page":"39","article-title":"Association of estrogen receptor-alpha A908G (K303R) mutation with breast cancer risk","volume":"6","author":"Abbasi","year":"2013","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1038\/onc.2009.520","article-title":"Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity","volume":"29","author":"Barone","year":"2010","journal-title":"Oncogene"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s10552-005-0307-5","article-title":"The estrogen receptor alpha gene and breast cancer risk (The Netherlands)","volume":"16","author":"Roest","year":"2005","journal-title":"Cancer Causes Control."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.maturitas.2006.06.003","article-title":"Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer","volume":"54","author":"Girault","year":"2006","journal-title":"Maturitas"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"22517","DOI":"10.1073\/pnas.1012820107","article-title":"Structural space of protein-protein interfaces is degenerate, close to complete, and highly connected","volume":"107","author":"Gao","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1110\/ps.0304803","article-title":"Analysis of accessible surface of residues in proteins","volume":"12","author":"Lins","year":"2003","journal-title":"Protein Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1093\/protein\/10.9.999","article-title":"Hydrogen bonds and salt bridges across protein-protein interfaces","volume":"10","author":"Xu","year":"1997","journal-title":"Protein Eng."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1161\/CIRCULATIONAHA.115.001593","article-title":"Machine Learning in Medicine","volume":"132","author":"Deo","year":"2015","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3233\/THC-151071","article-title":"Machine learning models in breast cancer survival prediction","volume":"24","author":"Montazeri","year":"2016","journal-title":"Technol. Health Care"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3781951","DOI":"10.1155\/2017\/3781951","article-title":"Involvement of Machine Learning for Breast Cancer Image Classification: A Survey","volume":"2017","author":"Nahid","year":"2017","journal-title":"Comput. Math. Methods Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6537","DOI":"10.12659\/MSM.910520","article-title":"Extreme Learning Machine (ELM)-Based Classification of Benign and Malignant Cells in Breast Cancer","volume":"24","author":"Toprak","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/978-1-4939-3578-9_17","article-title":"Introducing Machine Learning Concepts with WEKA","volume":"1418","author":"Smith","year":"2016","journal-title":"Methods Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/2962\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:59:11Z","timestamp":1760187551000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/12\/2962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,18]]},"references-count":66,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20122962"],"URL":"https:\/\/doi.org\/10.3390\/ijms20122962","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,6,18]]}}}