{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:20:41Z","timestamp":1785939641673,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Several pharmacogenetic-based decision support tools for psychoactive medication selection are available. However, the scientific evidence of the gene-drug pairs analyzed is mainly based on pharmacogenetic studies in patients with major depression or schizophrenia, and their clinical utility is mostly assessed in major depression. This study aimed at evaluating the impact of individual genes, with pharmacogenetic relevance in other psychiatric conditions, in the response to treatment in bipolar depression. Seventy-six patients diagnosed with bipolar disorder and an index major depressive episode were included in an observational retrospective study. Sociodemographic and clinical data were collected, and all patients were genotyped using a commercial multigene pharmacogenomic-based tool (Neuropharmagen\u00ae, AB-Biotics S.A., Barcelona, Spain). Multiple linear regression was used to identify pharmacogenetic and clinical predictors of efficacy and tolerability of medications. The pharmacogenetic variables response to serotonin-norepinephrine reuptake inhibitors (SNRIs) (ABCB1) and reduced metabolism of quetiapine (CYP3A4) predicted patient response to these medications, respectively. ABCB1 was also linked to the tolerability of SNRIs. An mTOR-related multigenic predictor was also associated with a lower number of adverse effects when including switch and autolytical ideation. Our results suggest that the predictors identified could be useful to guide the pharmacological treatment in bipolar disorder. Additional clinical studies are necessary to confirm these findings.<\/jats:p>","DOI":"10.3390\/genes12081259","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"1259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Variations Associated with Long-Term Treatment Response in Bipolar Depression"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6798-4054","authenticated-orcid":false,"given":"Gerard","family":"Anmella","sequence":"first","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1070-5533","authenticated-orcid":false,"given":"Silvia","family":"Vilches","sequence":"additional","affiliation":[{"name":"AB-Biotics, S.A., Av. de la Torre Blanca 57, 08172 Sant Cugat del Valles, Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Espadaler-Mazo","sequence":"additional","affiliation":[{"name":"AB-Biotics, S.A., Av. de la Torre Blanca 57, 08172 Sant Cugat del Valles, Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Murru","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Pacchiarotti","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquel","family":"Tuson","sequence":"additional","affiliation":[{"name":"AB-Biotics, S.A., Av. de la Torre Blanca 57, 08172 Sant Cugat del Valles, Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Garriga","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sol\u00e9","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e8","family":"Brat","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Fico","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-0053","authenticated-orcid":false,"given":"Eduard","family":"Vieta","sequence":"additional","affiliation":[{"name":"Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0140-6736(15)00241-X","article-title":"Bipolar disorder","volume":"387","author":"Grande","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1016\/S0140-6736(20)31544-0","article-title":"Bipolar disorders","volume":"396","author":"McIntyre","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1056\/NEJMra1906193","article-title":"Bipolar Disorder","volume":"383","author":"Carvalho","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1001\/archgenpsychiatry.2011.12","article-title":"Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative","volume":"68","author":"Merikangas","year":"2011","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/mp.2010.101","article-title":"Days out of role due to common physical and mental conditions: Results from the WHO World Mental Health surveys","volume":"16","author":"Alonso","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.jad.2011.04.055","article-title":"Gender differences in a cohort study of 604 bipolar patients: The role of predominant polarity","volume":"133","author":"Nivoli","year":"2011","journal-title":"J. Affect. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1001\/jama.2018.0322","article-title":"Preventing the malignant transformation of bipolar disorder","volume":"319","author":"Post","year":"2018","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.euroneuro.2020.03.017","article-title":"Symptom networks in acute depression across bipolar and major depressive disorders: A network analysis on a large, international, observational study","volume":"35","author":"Corponi","year":"2020","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3109\/15622975.2013.770551","article-title":"The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: Update 2012 on the long-term treatment of bipolar disorder","volume":"14","author":"Grunze","year":"2013","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_11","unstructured":"National Collaborating Centre for Mental Health (2021, August 15). Bipolar Disorder the Nice Guideline on the Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care Updated Edition. The British Psychological Society and The Royal College of Psychiatrist. Available online: https:\/\/www.nice.org.uk\/guidance\/cg185."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"pyw100","DOI":"10.1093\/ijnp\/pyw100","article-title":"The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm","volume":"20","author":"Fountoulakis","year":"2016","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1177\/0269881116636545","article-title":"Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology","volume":"30","author":"Goodwin","year":"2016","journal-title":"J. Psychopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.euroneuro.2019.09.007","article-title":"Expert advice on the management of valproate in women with bipolar disorder at childbearing age","volume":"29","author":"Anmella","year":"2019","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.biopsych.2012.10.030","article-title":"Contribution of common genetic variants to antidepressant response","volume":"73","author":"Tansey","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.2217\/pgs-2017-0104","article-title":"Advancing psychiatric pharmacogenomics using drug development paradigms","volume":"18","author":"Smith","year":"2017","journal-title":"Pharmacogenomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/YCO.0000000000000023","article-title":"Antidepressant pharmacogenetics","volume":"27","author":"Singh","year":"2014","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s40291-018-0335-y","article-title":"The Role of Pharmacogenomics in Bipolar Disorder: Moving Towards Precision Medicine","volume":"22","author":"Pisanu","year":"2018","journal-title":"Mol. Diagn. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41588-019-0397-8","article-title":"Genome-wide association study identifies 30 loci associated with bipolar disorder","volume":"51","author":"Stahl","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(16)00143-4","article-title":"Genetic variants associated with response to lithium treatment in bipolar disorder: A genome-wide association study","volume":"387","author":"Hou","year":"2016","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/428486a","article-title":"Medical genetics: A marker for Stevens-Johnson syndrome","volume":"428","author":"Chung","year":"2004","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/01.fpc.0000199500.46842.4a","article-title":"Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions","volume":"16","author":"Hung","year":"2006","journal-title":"Pharm. Genom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1056\/NEJMoa1013297","article-title":"HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans","volume":"364","author":"McCormack","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/cpt.1004","article-title":"Clinical Pharmacogenetics Implementation Consortium Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine: 2017 Update","volume":"103","author":"Phillips","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/epi.12564","article-title":"Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions","volume":"55","author":"Amstutz","year":"2014","journal-title":"Epilepsia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40345-020-00184-3","article-title":"Potential pharmacogenomic targets in bipolar disorder: Considerations for current testing and the development of decision support tools to individualize treatment selection","volume":"8","author":"McElroy","year":"2020","journal-title":"Int. J. Bipolar Disord."},{"key":"ref_28","first-page":"1","article-title":"Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: Results of a randomized, double-blind clinical trial","volume":"17","author":"Salavert","year":"2017","journal-title":"BMC Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"469","DOI":"10.9758\/cpn.2018.16.4.469","article-title":"A Pharmacogenomic-based Antidepressant Treatment for Patients with Major Depressive Disorder: Results from an 8-week, Randomized, Single-blinded Clinical Trial","volume":"16","author":"Han","year":"2018","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_30","first-page":"35","article-title":"The utility of pharmacogenetic testing to support the treatment of bipolar disorder","volume":"11","author":"Ielmini","year":"2018","journal-title":"Pharmgenomics Pers. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Callegari, C., Isella, C., Caselli, I., Poloni, N., and Ielmini, M. (2019). Pharmacogenetic Tests in Reducing Accesses to Emergency Services and Days of Hospitalization in Bipolar Disorder: A 2-Year Mirror Analysis. J. Pers. Med., 9.","DOI":"10.3390\/jpm9020022"},{"key":"ref_32","first-page":"301","article-title":"[A user-friendly scale for the short and long term outcome of bipolar disorder: The CGI-BP-M]","volume":"30","author":"Vieta","year":"2002","journal-title":"Actas Espa\u00f1olas Psiquiatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0022-3956(88)90024-6","article-title":"A new validation of the Hamilton Rating Scale for depression","volume":"22","year":"1988","journal-title":"J. Psychiatr. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1745-0179-3-5","article-title":"Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder","volume":"3","author":"Rosa","year":"2007","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"ref_35","unstructured":"RStudio Team (2020). RStudio: Integrated Development for R, RStudio, PBC. Available online: http:\/\/www.rstudio.com\/."},{"key":"ref_36","unstructured":"R Core Team (2018). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2217\/pgs-2019-0157","article-title":"The clinical utility of combinatorial pharmacogenomic testing for patients with depression: A meta-analysis","volume":"21","author":"Brown","year":"2020","journal-title":"Pharmacogenomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"645","DOI":"10.30773\/pi.2019.06.16","article-title":"Pharmacogenetics and depression: A critical perspective","volume":"16","author":"Corponi","year":"2019","journal-title":"Psychiatry Investig."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vilches, S., Tuson, M., Vieta, E., \u00c1lvarez, E., and Espadaler, J. (2019). Effectiveness of a pharmacogenetic tool at improving treatment efficacy in major depressive disorder: A meta-analysis of three clinical studies. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11090453"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fortinguerra, S., Sorrenti, V., Giusti, P., Zusso, M., and Buriani, A. (2020). Pharmacogenomic characterization in bipolar spectrum disorders. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010013"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.euroneuro.2021.03.008","article-title":"Bipolar disorder cohort studies: Crucial, but underfunded","volume":"47","author":"Vieta","year":"2021","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/FPC.0b013e3283385a1c","article-title":"Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein)","volume":"21","author":"Hodges","year":"2011","journal-title":"Pharm. Genom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.neuron.2007.11.017","article-title":"Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression","volume":"57","author":"Uhr","year":"2008","journal-title":"Neuron"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3410\/B1-23","article-title":"The ABCB1 transporter gene and antidepressant response","volume":"1","author":"Peters","year":"2009","journal-title":"F1000 Biol. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jpsychires.2015.11.010","article-title":"Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: Results from a randomized clinical study","volume":"73","author":"Breitenstein","year":"2016","journal-title":"J. Psychiatr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2217\/pgs.16.18","article-title":"ABCB1 genotyping in the treatment of depression","volume":"17","author":"Bruckl","year":"2016","journal-title":"Pharmacogenomics"},{"key":"ref_47","first-page":"332","article-title":"ABCB1 (MDR1) predicts remission on P-gp substrates in chronic depression","volume":"15","author":"Ray","year":"2015","journal-title":"Pharm. J."},{"key":"ref_48","first-page":"202","article-title":"A common polymorphism in the ABCB1 gene is associated with side effects of PGP-dependent antidepressants in a large naturalistic Dutch cohort","volume":"16","author":"Bet","year":"2016","journal-title":"Pharm. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1476-5381.2011.01557.x","article-title":"Interactions between antidepressants and P-glycoprotein at the blood-brain barrier: Clinical significance of in vitro and in vivo findings","volume":"165","author":"Dinan","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2131\/jts.38.349","article-title":"CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) is associated with reduced CYP3A4 protein level and function in human liver microsomes","volume":"38","author":"Okubo","year":"2013","journal-title":"J. Toxicol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2217\/pgs.12.187","article-title":"CYP3A4*22: Promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy","volume":"14","author":"Elens","year":"2013","journal-title":"Pharmacogenomics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1097\/JCP.0000000000000070","article-title":"The influence of the CYP3A4*22 polymorphism on serum concentration of quetiapine in psychiatric patients","volume":"34","year":"2014","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.euroneuro.2014.11.011","article-title":"Pharmacogenetic predictor of extrapyramidal symptoms induced by antipsychotics: Multilocus interaction in the mTOR pathway","volume":"25","author":"Mas","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s00228-006-0209-9","article-title":"The effect of variable cigarette consumption on the interaction with clozapine and olanzapine","volume":"62","author":"Haslemo","year":"2006","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e004216","DOI":"10.1136\/bmjopen-2013-004216","article-title":"Meta-analysis: The effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine","volume":"4","author":"Tsuda","year":"2014","journal-title":"BMJ Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1302\/2046-3758.49.2000571","article-title":"Interpreting regression models in clinical outcome studies","volume":"4","author":"Hamilton","year":"2015","journal-title":"Bone Jt. Res."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:46:28Z","timestamp":1760165188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/8\/1259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["genes12081259"],"URL":"https:\/\/doi.org\/10.3390\/genes12081259","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]}}}