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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Trace amine-associated receptors (TAARs) are a class of G protein-coupled receptors with roles in olfaction, behaviour, and immunity. Known best as an olfactory receptor, TAAR5 has been linked to emotional behaviour and hippocampal neurogenesis, yet its peripheral mechanisms remain poorly understood. Given bidirectional influences between the gut microbiota and the host, we investigated whether TAAR5 deletion alters the gut microbiome in mice. Using 16S rRNA sequencing, we compared the gut microbiota of TAAR5-knockout (TAAR5-KO) and wild-type mice. While alpha-diversity remained unchanged, beta-diversity analysis revealed significant separation between genotypes, with TAAR5-KO mice exhibiting markedly increased inter-individual variability. Taxonomically, KO mice showed a significant reduction in Ruminococcus and ASF356, alongside an enrichment of specific Lachnospiraceae and Prevotellaceae lineages. Functional metagenomic prediction (PICRUSt2) implied a reduction in the metagenomic capacity for central metabolic pathways (glycolysis, TCA cycle, fatty acid \u03b2-oxidation) and an increase in the capacity for guanosine nucleotide degradation pathways; these hypotheses remain untested. Molecular docking identified candidate microbial metabolites, including small amines (2-aminophenol, aminoacetone, butan-1-amine), with ligand efficiencies comparable to the known TAAR5 agonist trimethylamine. These findings suggest that TAAR5 may influence gut microbiome composition and function, with particular impact on Ruminococcus\u2014a genus linked to intestinal inflammation. The increased compositional variability in TAAR5-KO mice suggests that TAAR5 may act as a homeostatic gatekeeper in gut microbial ecology. Our in silico results offer testable hypotheses for future validation of microbial metabolites as novel TAAR5 ligands.<\/jats:p>","DOI":"10.3390\/ijms27198493","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:09:08Z","timestamp":1790161748000},"page":"8493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiome Alterations in TAAR5 Knockout Mice and In Silico Ligand Prediction"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-5486","authenticated-orcid":false,"given":"Ilya S.","family":"Zhukov","sequence":"first","affiliation":[{"name":"Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia"},{"name":"Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-0677","authenticated-orcid":false,"given":"Yazen","family":"Alnefeesi","sequence":"additional","affiliation":[{"name":"Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2732-5676","authenticated-orcid":false,"given":"Nikita S.","family":"Gladyshev","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2251-0896","authenticated-orcid":false,"given":"Alexey","family":"Zolkin","sequence":"additional","affiliation":[{"name":"Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9570-4769","authenticated-orcid":false,"given":"Alena B.","family":"Zalicheva","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9323-879X","authenticated-orcid":false,"given":"Yashar","family":"Chalabiani","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1085  Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildik\u00f3","family":"Miklya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1085  Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Ermolenko","sequence":"additional","affiliation":[{"name":"Institute of Experimental Medicine, 197376 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul R.","family":"Gainetdinov","sequence":"additional","affiliation":[{"name":"Institute of Translational Biomedicine, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1124\/pr.117.015305","article-title":"Trace Amines and Their Receptors","volume":"70","author":"Gainetdinov","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"msac006","DOI":"10.1093\/molbev\/msac006","article-title":"Evolution of Brain-Expressed Biogenic Amine Receptors into Olfactory Trace Amine-Associated Receptors","volume":"39","author":"Guo","year":"2022","journal-title":"Mol. Biol. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"eaax0396","DOI":"10.1126\/sciadv.aax0396","article-title":"A Transcriptomic Atlas of Mammalian Olfactory Mucosae Reveals an Evolutionary Influence on Food Odor Detection in Humans","volume":"5","author":"Saraiva","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70008","DOI":"10.1002\/sen2.70008","article-title":"Ligand Recognition and Function of TAARs","volume":"1","author":"Qian","year":"2025","journal-title":"Sens. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"177312","DOI":"10.1016\/j.ejphar.2025.177312","article-title":"Trace Amine Signaling in Zebrafish Models: CNS Pharmacology, Behavioral Regulation and Translational Relevance","volume":"991","author":"Galstyan","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41586-023-06106-4","article-title":"Structural Basis of Amine Odorant Perception by a Mammal Olfactory Receptor","volume":"618","author":"Guo","year":"2023","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.conb.2015.01.001","article-title":"Trace Amine-Associated Receptors: Ligands, Neural Circuits, and Behaviors","volume":"34","author":"Liberles","year":"2015","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/nature05066","article-title":"A Second Class of Chemosensory Receptors in the Olfactory Epithelium","volume":"442","author":"Liberles","year":"2006","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1134\/S1990519X25600279","article-title":"Effect of Chronic Unpredictable Mild Stress on TAAR2 Knockout Mice","volume":"19","author":"Efimova","year":"2025","journal-title":"Cell Tissue Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Efimova, E.V., Kuvarzin, S.R., Mor, M.S., Katolikova, N.V., Shemiakova, T.S., Razenkova, V., Ptukha, M., Kozlova, A.A., Murtazina, R.Z., and Smirnova, D. (2022). Trace Amine-Associated Receptor 2 Is Expressed in the Limbic Brain Areas and Is Involved in Dopamine Regulation and Adult Neurogenesis. Front. Behav. Neurosci., 16.","DOI":"10.3389\/fnbeh.2022.847410"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108373","DOI":"10.1016\/j.neuropharm.2020.108373","article-title":"Increased Dopamine Transmission and Adult Neurogenesis in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice","volume":"182","author":"Efimova","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shemiakova, T.S., Markina, A.A., Efimova, E.V., Murtazina, R.Z., Volnova, A.B., Veshchitskii, A.A., Leonova, E.I., and Gainetdinov, R.R. (2025). TAAR8 in the Brain: Implications for Dopaminergic Function, Neurogenesis, and Behavior. Biomedicines, 13.","DOI":"10.3390\/biomedicines13061391"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41388-023-02908-y","article-title":"From Odor to Oncology: Non-Canonical Odorant Receptors in Cancer","volume":"43","author":"Park","year":"2024","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s00418-019-01791-7","article-title":"TAAR1 Levels and Sub-Cellular Distribution Are Cell Line but Not Breast Cancer Subtype Specific","volume":"152","author":"Pitts","year":"2019","journal-title":"Histochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Vaganova, A.N., Maslennikova, D.D., Konstantinova, V.V., Kanov, E.V., and Gainetdinov, R.R. (2023). The Expression of Trace Amine-Associated Receptors (TAARs) in Breast Cancer Is Coincident with the Expression of Neuroactive Ligand\u2013Receptor Systems and Depends on Tumor Intrinsic Subtype. Biomolecules, 13.","DOI":"10.3390\/biom13091361"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1007\/s11481-011-9321-4","article-title":"Trace Amine Associated Receptor 1 Signaling in Activated Lymphocytes","volume":"7","author":"Panas","year":"2012","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1189\/jlb.0912433","article-title":"Biogenic Amines Activate Blood Leukocytes via Trace Amine-Associated Receptors TAAR1 and TAAR2","volume":"93","author":"Babusyte","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms22062942","article-title":"Genetic Deletion of Trace-Amine Associated Receptor 9 (TAAR9) in Rats Leads to Decreased Blood Cholesterol Levels","volume":"22","author":"Murtazina","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8658","DOI":"10.3390\/cimb46080510","article-title":"TAAR8 Mediates Increased Migrasome Formation by Cadaverine in RPE Cells","volume":"46","author":"Kim","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhukov, I.S., Kubarskaya, L.G., Karpova, I.V., Vaganova, A.N., Karpenko, M.N., and Gainetdinov, R.R. (2021). Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (Taar5) Knockout Mice. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147307"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.pharmthera.2017.07.002","article-title":"Pharmacology of Human Trace Amine-Associated Receptors: Therapeutic Opportunities and Challenges","volume":"180","author":"Berry","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-020-2395-5","article-title":"A Neurotransmitter Produced by Gut Bacteria Modulates Host Sensory Behaviour","volume":"583","author":"Fox","year":"2020","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10571-019-00772-7","article-title":"Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1)","volume":"40","author":"Olliffe","year":"2020","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wallrabenstein, I., Kuklan, J., Weber, L., Zborala, S., Werner, M., Altm\u00fcller, J., Becker, C., Schmidt, A., Hatt, H., and Hummel, T. (2013). Human Trace Amine-Associated Receptor TAAR5 Can Be Activated by Trimethylamine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054950"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00441-009-0859-x","article-title":"Anatomical and Histological Profiling of Orphan G-Protein-Coupled Receptor Expression in Gastrointestinal Tract of C57BL\/6J Mice","volume":"338","author":"Ito","year":"2009","journal-title":"Cell Tissue Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-02289-w","article-title":"Role of the Trace Amine Associated Receptor 5 (TAAR5) in the Sensorimotor Functions","volume":"11","author":"Kalinina","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S52","DOI":"10.1093\/ibd\/izae282.124","article-title":"Microbial Trimethylamine Host Trace Amine Associated Receptor 5 (Taar5) Signaling Exerts Pro-Fibrotic Properties in Ibd","volume":"31","author":"Massey","year":"2025","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcdb.2023.01.006","article-title":"Gut Immune Cells and Intestinal Niche Imprinting","volume":"150\u2013151","author":"Rivera","year":"2023","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s41385-021-00389-4","article-title":"Human Gut-Associated Lymphoid Tissues (GALT); Diversity, Structure, and Function","volume":"14","author":"Fenton","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41385-019-0192-y","article-title":"The Antibody\/Microbiota Interface in Health and Disease","volume":"13","author":"Sterlin","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1038\/s12276-023-01088-9","article-title":"Unconventional Immune Cells in the Gut Mucosal Barrier: Regulation by Symbiotic Microbiota","volume":"55","author":"Yoo","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101806","DOI":"10.1016\/j.smim.2023.101806","article-title":"B Cells and the Intestinal Microbiome in Time, Space and Place","volume":"69","author":"Pabst","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.4049\/jimmunol.159.9.4330","article-title":"Mechanism for Enhanced External Transfer of Dimeric IgA over Pentameric IgM: Studies of Diffusion, Binding to the Human Polymeric Ig Receptor, and Epithelial Transcytosis","volume":"159","author":"Natvig","year":"1997","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhukov, I.S., Vaganova, A.N., Murtazina, R.Z., Alferova, L.S., Ermolenko, E.I., and Gainetdinov, R.R. (2022). Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats. Biomolecules, 12.","DOI":"10.3390\/biom12121823"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vaganova, A.N., Zhukov, I.S., Shemiakova, T.S., Rozhkov, K.A., Alferova, L.S., Karaseva, A.B., Ermolenko, E.I., and Gainetdinov, R.R. (2024). Functional Analysis of TAAR1 Expression in the Intestine Wall and the Effect of Its Gene Knockout on the Gut Microbiota in Mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252313216"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6667","DOI":"10.1021\/acs.jcim.3c00755","article-title":"Structure-Based Discovery of Mouse Trace Amine-Associated Receptor 5 Antagonists","volume":"63","author":"Nicoli","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"RP107037","DOI":"10.7554\/eLife.107037.3","article-title":"Gut Microbe-Derived Trimethylamine Shapes Circadian Rhythms through the Host Receptor TAAR5","volume":"14","author":"Mahen","year":"2026","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.62641\/aep.v53i5.1916","article-title":"Trace Amine-Associated Receptors (TAARs): Candidate Targets in the Treatment of Bipolar Disorders","volume":"53","author":"Alnefeesi","year":"2025","journal-title":"Actas Esp. Psiquiatr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhukov, I.S., Karpova, I.V., Murtazina, R.Z., Alnefeesi, Y., Korenkova, O.M., Tissen, I.Y., Palchikova, S.A., Tokareva, L.A., Pyurveev, S.S., and Shabanov, P.D. (2025). TAAR9 Knockout Increases Hippocampal Serotonin and Alters Grooming Behavior in Rats. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1684029"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e63998","DOI":"10.7554\/eLife.63998","article-title":"Gut Microbe-Targeted Choline Trimethylamine Lyase Inhibition Improves Obesity via Rewiring of Host Circadian Rhythms","volume":"11","author":"Schugar","year":"2022","journal-title":"eLife"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"100593","DOI":"10.1016\/j.bj.2023.04.001","article-title":"Hyperammonemia Induces Microglial NLRP3 Inflammasome Activation via Mitochondrial Oxidative Stress in Hepatic Encephalopathy","volume":"46","author":"Cheon","year":"2023","journal-title":"Biomed. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/imr.12833","article-title":"Urate-Induced Immune Programming: Consequences for Gouty Arthritis and Hyperuricemia","volume":"294","author":"Popp","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, D., Yuan, S., Deng, Y., Wang, X., Wu, S., Chen, X., Li, Y., Ouyang, J., Lin, D., and Quan, H. (2023). The Dysregulation of Immune Cells Induced by Uric Acid: Mechanisms of Inflammation Associated with Hyperuricemia and Its Complications. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1282890"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12672","DOI":"10.1073\/pnas.1904099116","article-title":"Ruminococcus Gnavus, a Member of the Human Gut Microbiome Associated with Crohn\u2019s Disease, Produces an Inflammatory Polysaccharide","volume":"116","author":"Henke","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"115018","DOI":"10.1016\/j.celrep.2024.115018","article-title":"Genomic Features and Prevalence of Ruminococcus Species in Humans Are Associated with Age, Lifestyle, and Disease","volume":"43","author":"Valentino","year":"2024","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Silva, I., and da Silva, M.T.B. (2025). Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment. J. Clin. Med., 14.","DOI":"10.3390\/books978-3-7258-5706-7"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-Resolution Sample Inference from Illumina Amplicon Data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1093\/bioinformatics\/bts252","article-title":"SINA: Accurate High-Throughput Multiple Sequence Alignment of Ribosomal RNA Genes","volume":"28","author":"Pruesse","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/s41587-020-0548-6","article-title":"PICRUSt2 for Prediction of Metagenome Functions","volume":"38","author":"Douglas","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"McDonald, A.G., Boyce, S., and Tipton, K.F. (2015). Enzyme Classification and Nomenclature. Encyclopedia of Life Sciences, John Wiley & Sons, Ltd.","DOI":"10.1002\/9780470015902.a0000710.pub3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: Biological Systems Database as a Model of the Real World","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2013). Phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061217"},{"key":"ref_53","first-page":"100388","article-title":"MicrobiotaProcess: A Comprehensive R Package for Deep Mining Microbiome","volume":"4","author":"Xu","year":"2023","journal-title":"Innovation"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Oksanen, J., Simpson, G.L., Blanchet, F.G., Kindt, R., Legendre, P., Minchin, P.R., O\u2019Hara, R.B., Solymos, P., Stevens, M.H.H., and Szoecs, E. (2001). Vegan: Community Ecology Package 2001, CRAN.","DOI":"10.32614\/CRAN.package.vegan"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Kolde, R. (2010). Pheatmap: Pretty Heatmaps, 2010, CRAN.","DOI":"10.32614\/CRAN.package.pheatmap"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"gkaf018","DOI":"10.1093\/nar\/gkaf018","article-title":"EdgeR v4: Powerful Differential Analysis of Sequencing Data with Expanded Functionality and Improved Support for Small Counts and Larger Datasets","volume":"53","author":"Chen","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:11:56Z","timestamp":1790161916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":57,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198493"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198493","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]}}}