{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:00:38Z","timestamp":1780524038624,"version":"3.54.1"},"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K12DK100022"],"award-info":[{"award-number":["K12DK100022"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001458","name":"American Kennel Club Canine Health Foundation","doi-asserted-by":"publisher","award":["02703"],"award-info":[{"award-number":["02703"]}],"id":[{"id":"10.13039\/100001458","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bee Hanlon\/JoAnne Schmidt O\u2019Brien Fellowship"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hypertriglyceridemia (HTG) is influenced by multiple genetic and environmental factors. Spontaneous, idiopathic HTG is common in the Miniature Schnauzer dog and presumed to have a strong genetic influence in this breed. To define genes that are differentially expressed in dogs with HTG, we performed RNA sequencing on peripheral blood of 13 Miniature Schnauzers with HTG and 18 controls. We identified 110 differentially expressed genes (DEGs). Pathway analysis suggests an ongoing pro-thrombotic, endothelial activation process in dogs with HTG. The gene with the largest fold change (5.4 \u00b1 1.4, P<jats:sub>adj<\/jats:sub> = 4.4E-04), <jats:italic>SERPINE1<\/jats:italic>, encodes plasminogen activator inhibitor 1 (PAI-1), a known risk factor for atherosclerosis and thrombosis. Other top DEGs, including <jats:italic>SHANK3<\/jats:italic>, <jats:italic>MMRN1<\/jats:italic>, and <jats:italic>FZD7<\/jats:italic>, are involved in endothelial activation. Two of the top DEGs, <jats:italic>ARHGAP29<\/jats:italic> and <jats:italic>ARHGAP21<\/jats:italic>, inhibit pro-thrombotic pathways and are potentially protective of disease sequelae. Top DEGs, including <jats:italic>SERPINE1<\/jats:italic> and <jats:italic>ARHGAP21<\/jats:italic>, have also been linked to metabolic syndrome or its features (e.g. insulin resistance) in humans and animal models. Our findings indicate that HTG in the Miniature Schnauzer dog has similar features to HTG and metabolic syndrome in humans, highlighting the potential use of the dog as a spontaneous model for further research into the etiology and effects of HTG.<\/jats:p>","DOI":"10.1371\/journal.pone.0313343","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T18:22:53Z","timestamp":1731435773000},"page":"e0313343","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Whole blood gene expression analysis of spontaneous hypertriglyceridemia in dogs suggests an underlying pro-thrombotic process"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4836-7720","authenticated-orcid":true,"given":"Lauren A.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5472-5088","authenticated-orcid":true,"given":"Katie M.","family":"Minor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Tate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-2354","authenticated-orcid":true,"given":"Eva","family":"Furrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"pone.0313343.ref001","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s40119-020-00170-x","article-title":"Prevalence of US Adults with Triglycerides \u2265 150 mg\/dl: NHANES 2007\u20132014","volume":"9","author":"W. Fan","year":"2020","journal-title":"Cardiol Ther"},{"issue":"8","key":"pone.0313343.ref002","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1503\/cmaj.060963","article-title":"Hypertriglyceridemia: its etiology, effects, and treatment","volume":"176","author":"G. Yuan","year":"2007","journal-title":"CMAJ"},{"key":"pone.0313343.ref003","volume-title":"Endotext","author":"A. Chait","year":"2019"},{"issue":"1","key":"pone.0313343.ref004","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1210\/er.2014-1062","article-title":"Hypertriglyceridemia in the genomic era: a new paradigm","volume":"36","author":"G.F. Lewis","year":"2015","journal-title":"Endocr Rev"},{"key":"pone.0313343.ref005","doi-asserted-by":"crossref","first-page":"m3109","DOI":"10.1136\/bmj.m3109","article-title":"Management of hypertriglyceridemia","volume":"371","author":"V. Simha","year":"2020","journal-title":"BMJ"},{"issue":"8","key":"pone.0313343.ref006","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S2213-8587(13)70191-8","article-title":"The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management","volume":"2","author":"R.A. Hegele","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"pone.0313343.ref007","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jacl.2018.10.006","article-title":"Severe hypertriglyceridemia is primarily polygenic","volume":"13","author":"J.S. Dron","year":"2019","journal-title":"J Clin Lipidol"},{"key":"pone.0313343.ref008","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jacl.2020.01.003","article-title":"The polygenic nature of mild-to-moderate hypertriglyceridemia","volume":"14","author":"J.S. Dron","year":"2020","journal-title":"J Clin Lipidol"},{"issue":"6","key":"pone.0313343.ref009","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1111\/j.1939-1676.2007.tb01942.x","article-title":"Investigation of hypertriglyceridemia in healthy Miniature Schnauzers","volume":"21","author":"P.G. Xenoulis","year":"2008","journal-title":"J Vet Intern Med"},{"key":"pone.0313343.ref010","doi-asserted-by":"crossref","first-page":"105559","DOI":"10.1016\/j.tvjl.2020.105559","article-title":"Sequence analysis of the coding regions of the apolipoprotein C2 (APOC2) gene in Miniature Schnauzers with idiopathic hypertriglyceridemia","volume":"265","author":"P.G. Xenoulis","year":"2020","journal-title":"Vet J"},{"issue":"2","key":"pone.0313343.ref011","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3390\/genes15020193","article-title":"Sequence analysis of six candidate genes in Miniature Schnauzers with primary hypertriglyceridemia","volume":"15","author":"N.M. Tate","year":"2024","journal-title":"Genes (Basel)"},{"issue":"9","key":"pone.0313343.ref012","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1746-6148-9-47","article-title":"Novel lipoprotein density profiling in healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with hyperlipidemia","volume":"8","author":"P.G. Xenoulis","year":"2013","journal-title":"BMC Vet Res"},{"issue":"2","key":"pone.0313343.ref013","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/jvim.17010","article-title":"Clustering analysis of lipoprotein profiles to identify subtypes of hypertriglyceridemia in Miniature Schnauzers","volume":"38","author":"N.M. Tate","year":"2024","journal-title":"J Vet Intern Med"},{"key":"pone.0313343.ref014","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.tvjl.2016.04.009","article-title":"Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia","volume":"212","author":"E. Furrow","year":"2016","journal-title":"Vet J"},{"issue":"1","key":"pone.0313343.ref015","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/j.1939-1676.2010.0644.x","article-title":"Serum triglyceride concentrations in Miniature Schnauzers with and without a history of probable pancreatitis","volume":"25","author":"P.G. Xenoulis","year":"2011","journal-title":"J Vet Intern Med"},{"issue":"1","key":"pone.0313343.ref016","first-page":"63","article-title":"Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia","volume":"232","author":"P.G. Xenoulis","year":"2008","journal-title":"J Vet Intern Med"},{"issue":"3","key":"pone.0313343.ref017","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/jvim.16418","article-title":"Associations among serum insulin, calprotectin, and c-reactive protein concentrations in Miniature Schnauzers with idiopathic hyperlipidemia before and after feeding an ultra-low-fat diet","volume":"36","author":"P.G. Xenoulis","year":"2022","journal-title":"J Vet Intern Med"},{"issue":"5","key":"pone.0313343.ref018","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1248\/bpb.24.579","article-title":"The relationship between plasma high density lipoprotein cholesterol levels and cholesteryl ester transfer protein activity in six species of health experimental animals","volume":"24","author":"K. Tsutsumi","year":"2001","journal-title":"Biol Pharm Bull"},{"issue":"7","key":"pone.0313343.ref019","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.cell.2017.05.038","article-title":"An expanded view of complex traits: from polygenic to omnigenic","volume":"169","author":"E.A. Boyle","year":"2018","journal-title":"Cell"},{"issue":"2","key":"pone.0313343.ref020","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.coph.2005.01.007","article-title":"Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes, and cardiovascular disease","volume":"5","author":"B. De Taeye","year":"2005","journal-title":"Curr Opin Pharmacol"},{"key":"pone.0313343.ref021","doi-asserted-by":"crossref","first-page":"622473","DOI":"10.3389\/fcvm.2020.622473","article-title":"Targeting PAI-1 in cardiovascular disease: Structural insights into PAI-1 functionality and inhibition","volume":"7","author":"M. Sillen","year":"2020","journal-title":"Front Cardiovasc Med"},{"issue":"1","key":"pone.0313343.ref022","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1161\/01.ATV.18.1.20","article-title":"Very-low-density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia","volume":"18","author":"P. Eriksson","year":"1998","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"3\u20134","key":"pone.0313343.ref023","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000093221","article-title":"Effects of VLDL and remnant particles on platelets","volume":"35","author":"R. Olufadi","year":"2006","journal-title":"Pathophysiol Haemost Thromb"},{"key":"pone.0313343.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.rvsc.2016.11.004","article-title":"Development of a plasminogen activator inhibitor (PAI-1) assay and comparison of plasma PAI-1 activity in hyperlipidemic\/dyslipidemic dogs with either hyperadrenocorticism or diabetes mellitus, and healthy dogs","volume":"111","author":"C.J. Wong","year":"2017","journal-title":"Res Vet Sci"},{"issue":"2","key":"pone.0313343.ref025","doi-asserted-by":"crossref","first-page":"e32204","DOI":"10.1371\/journal.pone.0032204","article-title":"Matrix-bound PAI-1 supports cell blebbing via RhoA\/ROCK1 signaling","volume":"7","author":"A. Cartier-Michaud","year":"2012","journal-title":"PLOS One"},{"issue":"4","key":"pone.0313343.ref026","doi-asserted-by":"crossref","first-page":"165","DOI":"10.4103\/0975-3583.74258","article-title":"The role of RhoA\/Rho kinase pathway in endothelial dysfunction","volume":"1","author":"L. Yao","year":"2010","journal-title":"J Cardiovasc Dis Res"},{"key":"pone.0313343.ref027","doi-asserted-by":"crossref","first-page":"820945","DOI":"10.3389\/fcvm.2021.820945","article-title":"Turning platelets off and on: role of RhoGAPs and RhoGEFs in platelet activity","volume":"8","author":"S.P. Comer","year":"2021","journal-title":"Front Cardiovasc Med"},{"issue":"28","key":"pone.0313343.ref028","doi-asserted-by":"crossref","first-page":"11427","DOI":"10.1073\/pnas.1306595110","article-title":"Rasip1 mediates Rap1 regulation of Rho in endothelial barrier function through ArhGAP29","volume":"110","author":"A. Post","year":"2013","journal-title":"Proc Natl Acad Sci U.S.A"},{"issue":"6","key":"pone.0313343.ref029","doi-asserted-by":"crossref","first-page":"119012","DOI":"10.1016\/j.bbamcr.2021.119012","article-title":"Deficiency of ARHGAP21 alters magakeryocytic cell lineage responses and enhances platelet hemostatic function","volume":"1868","author":"V.A. Bernusso","year":"2021","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"issue":"3","key":"pone.0313343.ref030","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1006\/bbrc.2000.4194","article-title":"cGMP-dependent protein kinase phosphorylates and inactivates RhoA","volume":"280","author":"N. Sawada","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0313343.ref031","doi-asserted-by":"crossref","first-page":"8835","DOI":"10.1038\/s41598-022-12749-6","article-title":"Proteomic profiling of concurrently isolated primary microvascular endothelial cells, pericytes, and vascular smooth. Muscle cells from adult mouse heart","volume":"12","author":"Z. Cao","year":"2022","journal-title":"Sci Rep"},{"issue":"3","key":"pone.0313343.ref032","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/jnc.15014","article-title":"Truncating mutations in SHANK3 associated with global developmental delay interfere with nuclear \u00df-catenin signaling","volume":"155","author":"F.H. Nia","year":"2020","journal-title":"J Neurochem"},{"issue":"2","key":"pone.0313343.ref033","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/jth.15171","article-title":"Multimerin 1 supports platelet function in vivo and binds to specific GAPGPOGPX motifs in fibrillar collagens that inhance platelet adhesion","volume":"19","author":"A. Leatherdale","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"2","key":"pone.0313343.ref034","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/cvr\/cvu133","article-title":"Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes","volume":"103","author":"N.F. Tojais","year":"2014","journal-title":"Cardiovasc Res"},{"issue":"1","key":"pone.0313343.ref035","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12987-021-00278-9","article-title":"Activation of Frizzled-7 attenuates blood-brain barrier disruption through Dvl\/\u00df-catenin\/WISP1 signaling pathway after intracerebral hemorrhage in mice","volume":"18","author":"W. He","year":"2021","journal-title":"Fluids Barriers CNS"},{"issue":"6","key":"pone.0313343.ref036","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1161\/ATVBAHA.107.140913","article-title":"Low levels of Nogo-B in human carotid atherosclerotic plaques are associated with an atheromatous phenotype, restenosis, and stenosis severity","volume":"27","author":"J.A. Rodriguez-Feo","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"7","key":"pone.0313343.ref037","doi-asserted-by":"crossref","first-page":"4535","DOI":"10.4049\/jimmunol.172.7.4535","article-title":"Adenoviral gene delivery of elafin and secretory leukocyte protease inhibitor attenuates NF-kappa B-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli","volume":"172","author":"P.A. Henriksen","year":"2004","journal-title":"J Immunol"},{"issue":"5","key":"pone.0313343.ref038","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1111\/apt.15163","article-title":"Shared disease mechanisms between non-alcoholic fatty liver disease and metabolic syndrome\u2013translating knowledge from systems biology to the bedside","volume":"49","author":"S. Sookoian","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"issue":"10","key":"pone.0313343.ref039","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1161\/01.ATV.0000242905.41404.68","article-title":"PAI-1 and the metabolic syndrome: links, causes, and consequences","volume":"26","author":"M.C. Alessi","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"pone.0313343.ref040","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1743-7075-4-28","article-title":"Do inflammation and procoagulation biomarkers contribute to the metabolic syndrome cluster?","volume":"4","author":"A.T. Kraja","year":"2007","journal-title":"Nutr Metab (Lond)"},{"key":"pone.0313343.ref041","doi-asserted-by":"crossref","first-page":"9596054","DOI":"10.1155\/2018\/9596054","article-title":"Plasminogen activator inhibitor-1 level correlates with lipoprotein subfractions in obese nondiabetic subjects","volume":"2018","author":"S. Somodi","year":"2018","journal-title":"Int J Endocrinol"},{"issue":"1","key":"pone.0313343.ref042","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41598-020-79948-x","article-title":"Role of PAI-1 in hepatic steatosis and dyslipidemia","volume":"11","author":"J.A. Levine","year":"2021","journal-title":"Sci Rep"},{"issue":"9","key":"pone.0313343.ref043","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1089\/met.2015.0061","article-title":"Increased RhoA\/Rho-kinase activity and markers of endothelial dysfunction in young adult subjects with metabolic syndrome","volume":"13","author":"A. Leguina-Ruzzi","year":"2015","journal-title":"Metab Syndr Relat Disord"},{"issue":"9","key":"pone.0313343.ref044","doi-asserted-by":"crossref","first-page":"7112","DOI":"10.1002\/jcp.26527","article-title":"Whole body ARHGAP21 reduction improves glucose homeostasis in high-fat diet obese mice","volume":"233","author":"G.M. Soares","year":"2018","journal-title":"J Cell Physiol"},{"key":"pone.0313343.ref045","doi-asserted-by":"crossref","first-page":"100242","DOI":"10.1016\/j.metop.2023.100242","article-title":"Aldehyde dehydrogenase 2 polymorphism is an important gene for insulin resistance in Japanese patients with type 2 diabetes","volume":"18","author":"T. Okura","year":"2023","journal-title":"Metabol Open"},{"issue":"6","key":"pone.0313343.ref046","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.3390\/genes14061131","article-title":"Genome-wide integrative transcriptional profiling identifies age-associated signatures in dogs","volume":"14","author":"H.S. Kim","year":"2023","journal-title":"Genes (Basel)"},{"issue":"6450","key":"pone.0313343.ref047","doi-asserted-by":"crossref","first-page":"eeaw7317","DOI":"10.1126\/science.aaw7317","article-title":"Conservation, acquisition, and functional impact of sex-biased gene expression in mammals","volume":"365","author":"S. Naqvi","year":"2019","journal-title":"Science"},{"issue":"4","key":"pone.0313343.ref048","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1939-1676.1993.tb01016.x","article-title":"Untracentrifugal and electrophoretic characteristics of the plasma lipoproteins of Miniature Schnauzer dogs with idiopathic hyperlipoproteinemia","volume":"7","author":"M.S. Whitney","year":"1993","journal-title":"J Vet Intern Med"},{"issue":"2","key":"pone.0313343.ref049","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3390\/genes15020190","article-title":"Understanding hypertriglyceridemia: Integrating genetic insights","volume":"15","author":"M. Alves","year":"2024","journal-title":"Genes"},{"key":"pone.0313343.ref050","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1152\/japplphysiol.00316.2004","article-title":"Effects of exercise on gene expression in human peripheral blood mononuclear cells","volume":"97","author":"P.H. Connolly","year":"2004","journal-title":"J Appl Physiol"},{"issue":"4","key":"pone.0313343.ref051","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s13668-015-0143-5","article-title":"Whole-blood gene expression profiles in large-scale epidemiological studies: What do they tell?","volume":"4","author":"K.S. Olsen","year":"2015","journal-title":"Curr Nutr Rep"},{"issue":"1","key":"pone.0313343.ref052","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/ajcn\/87.1.97","article-title":"A low-glycemic-index diet reduces plasma plasminogen activator inhibitor-1 activity, but not tissue inhibitor of proteinases-1 or plasminogen activator inhibitor-1 protein, in overweight women","volume":"87","author":"L. Jensen","year":"2008","journal-title":"Am J Cln Nutr"},{"key":"pone.0313343.ref053","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1758-5996-2-7","article-title":"Sedentary subjects have higher PAI-1 and lipoproteins levels than highly trained athletes","volume":"2","author":"F.S. Lira","year":"2010","journal-title":"Diabetol Metab Syndr"},{"issue":"23","key":"pone.0313343.ref054","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1111\/bph.14931","article-title":"Hyperlipidaemia and cardioprotection: Animal models for translational studies","volume":"177","author":"I. Andreadou","year":"2020","journal-title":"Br J Pharmacol"},{"issue":"4","key":"pone.0313343.ref055","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/nsr\/nwz068","article-title":"Dog10K: the international consortium of canine genome sequencing","volume":"6","author":"G.D. Wang","year":"2019","journal-title":"Natl Sci Rev"},{"issue":"6","key":"pone.0313343.ref056","doi-asserted-by":"crossref","first-page":"e0269425","DOI":"10.1371\/journal.pone.0269425","article-title":"Cohort profile: The Golden Retriever Lifetime Study (GRLS)","volume":"17","author":"J. Labadie","year":"2022","journal-title":"PLoS One"},{"issue":"7895","key":"pone.0313343.ref057","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41586-021-04282-9","article-title":"Dog Aging Project Consortium. An open science study of ageing in companion dogs","volume":"602","author":"K.E. Creevey","year":"2022","journal-title":"Nature"},{"issue":"6","key":"pone.0313343.ref058","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1111\/jvim.14833","article-title":"Clinical consequences of hypertriglyceridemia-associated proteinuria in Miniature Schnauzers","volume":"31","author":"R.E. Smith","year":"2017","journal-title":"J Vet Intern Med"},{"key":"pone.0313343.ref059","unstructured":"R Core Team (2021). R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL: https:\/\/R-project.org."},{"key":"pone.0313343.ref060","volume-title":"Proceedings of the Practice and Experience in Advanced Research Computing on Rise of the Machines (learning)","author":"J. Baller","year":"2019"},{"key":"pone.0313343.ref061","volume-title":"FastQC: a quality control tool for high throughput sequence data","author":"B. Bioinformatics","year":"2011"},{"issue":"15","key":"pone.0313343.ref062","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"A.M. Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"pone.0313343.ref063","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"D. Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"pone.0313343.ref064","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"M.I. Love","year":"2014","journal-title":"Genome Biol"},{"key":"pone.0313343.ref065","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"18","author":"Z. Gu","year":"2016","journal-title":"Bioinformatics"},{"issue":"7","key":"pone.0313343.ref066","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":"M.E. Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pone.0313343.ref067","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1756-0500-4-36","article-title":"Leukocyte count affects expression of reference genes in canine whole blood samples","volume":"4","author":"C.J. Piek","year":"2011","journal-title":"BMC Res Notes"},{"key":"pone.0313343.ref068","doi-asserted-by":"crossref","first-page":"W71","DOI":"10.1093\/nar\/gkm306","article-title":"Primer3Plus, an enhanced web interface to Primer3","volume":"35","author":"A. Untergasser","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"pone.0313343.ref069","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"E.Y. Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"issue":"W1","key":"pone.0313343.ref070","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":"M.V. Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pone.0313343.ref071","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1002\/cpz1.90","article-title":"Gene set knowledge discovery with Enrichr","volume":"1","author":"Z. Xie","year":"2021","journal-title":"Curr Protoc"},{"issue":"D1","key":"pone.0313343.ref072","first-page":"D687","volume":"50","author":"M. Gillespie","year":"2022","journal-title":"The reactome pathway knowledgebase"},{"key":"pone.0313343.ref073","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3389\/fphar.2019.00445","article-title":"The NCATS BioPlanet\u2013An integrated platform for exploring the universe of cellular signaling pathways for toxicology, systems biology, and chemical genomics","volume":"10","author":"R. Huang","year":"2019","journal-title":"Front Pharmacol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T18:23:13Z","timestamp":1731435793000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313343"}},"subtitle":[],"editor":[{"given":"Ulrike Gertrud","family":"Munderloh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":73,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313343","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]}}}