{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:16:56Z","timestamp":1771233416738,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,7]],"date-time":"2019-12-07T00:00:00Z","timestamp":1575676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteochondrosis is a failure of the endochondral ossification that affects developing joints in humans and several animal species. It is a localized idiopathic joint disorder characterized by focal chondronecrosis and growing cartilage retention, which can lead to the formation of fissures, subchondral bone cysts, or intra-articular fragments. Osteochondrosis is a complex multifactorial disease associated with extracellular matrix alterations and failure in chondrocyte differentiation, mainly due to genetic, biochemical, and nutritional factors, as well as traumas. This study describes the main proteomic alterations occurring in chondrocytes isolated from osteochondrotic cartilage fragments. A comparative analysis performed on equine osteochondrotic and healthy chondrocytes showed 26 protein species as differentially represented. In particular, quantitative changes in the extracellular matrix, cytoskeletal and chaperone proteins, and in cell adhesion and signaling molecules were observed in osteochondrotic cells, compared to healthy controls. Functional group analysis annotated most of these proteins in \u201cgrowth plate and cartilage development\u201d, while others were included in \u201cglycolysis and gluconeogenesis\u201d, \u201cpositive regulation of protein import\u201d, \u201ccell\u2013cell adhesion mediator activity\u201d, and \u201cmitochondrion nucleoid\u201d. These results may help to clarify some chondrocyte functional alterations that may play a significant role in determining the onset and progression of equine osteochondrosis and, being related, of human juvenile osteochondrosis.<\/jats:p>","DOI":"10.3390\/ijms20246179","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T05:54:51Z","timestamp":1575870891000},"page":"6179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Proteome Alterations in Equine Osteochondrotic Chondrocytes"],"prefix":"10.3390","volume":"20","author":[{"given":"Elisabetta","family":"Chiaradia","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Pepe","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Luigi","family":"Orvietani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Renzone","sequence":"additional","affiliation":[{"name":"ISPAAM, National Research Council, 80147 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-6226","authenticated-orcid":false,"given":"Alessandro","family":"Magini","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-6540","authenticated-orcid":false,"given":"Monica","family":"Sforna","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Emiliani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy"},{"name":"CEMIN-Center of Excellence for Innovative Nanostructured Material, 06123 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Di Meo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Scaloni","sequence":"additional","affiliation":[{"name":"ISPAAM, National Research Council, 80147 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1354\/vp.44-4-429","article-title":"Etiology and pathogenesis of osteochondrosis","volume":"44","author":"Ytrehus","year":"2007","journal-title":"Vet. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.csm.2013.11.004","article-title":"Emerging genetic basis of osteochondritis dissecans","volume":"33","author":"Bates","year":"2014","journal-title":"Clin. Sports Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/evj.12824","article-title":"Genetic risk factors for osteochondrosis in various horse breeds","volume":"50","author":"Naccache","year":"2018","journal-title":"Equine Vet. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.tvjl.2013.03.048","article-title":"Problems and pointers in osteochondrosis: Twenty years on","volume":"197","author":"Jeffcott","year":"2013","journal-title":"Vet. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/evj.12821","article-title":"Fifty years of osteochondrosis","volume":"50","year":"2018","journal-title":"Equine Vet. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1177\/0300985815588778","article-title":"An Update on the Pathogenesis of Osteochondrosis","volume":"52","author":"Olstad","year":"2015","journal-title":"Vet. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1016\/j.joca.2013.08.011","article-title":"Articular Osteochondrosis: A Comparison of Naturally Occurring Human and Animal Disease","volume":"21","author":"McCoy","year":"2013","journal-title":"Osteoarthr. Cartil."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s12015-019-09875-6","article-title":"Osteochondritis dissecans (OCD) in Horses\u2014Molecular Background of its Pathogenesis and Perspectives for Progenitor Stem Cell Therapy","volume":"15","author":"Bourebaba","year":"2019","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.csm.2017.02.001","article-title":"Basic Science of Articular Cartilage","volume":"36","author":"Carballo","year":"2017","journal-title":"Clin. Sports Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1586\/14789450.2015.1065182","article-title":"Lessons from the proteomic study of osteoarthritis","volume":"12","author":"Calamia","year":"2015","journal-title":"Expert Rev. Proteom."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1080\/14789450.2017.1321481","article-title":"Defining the proteomic landscape of rheumatoid arthritis: Progress and prospective clinical applications","volume":"14","author":"Lourido","year":"2017","journal-title":"Expert Rev. Proteom."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.joca.2016.12.016","article-title":"Osteoarthritis Year in Review 2016: Biomarkers (biochemical markers)","volume":"25","author":"Mobasheri","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/14789450.2019.1571918","article-title":"Understanding the role of chondrocytes in osteoarthritis: Utilizing proteomics","volume":"16","author":"Trachana","year":"2019","journal-title":"Expert Rev. Proteom."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.yexmp.2014.03.004","article-title":"Involvement of mitochondrial dysfunction and ER-stress in the physiopathology of equine osteochondritis dissecans (OCD)","volume":"96","author":"Desjardin","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Desjardin, C., Riviere, J., Vaiman, A., Morgenthaler, C., Diribarne, M., Zivy, M., Robert, C., Le Moyec, L., Wimel, L., and Lepage, O. (2014). Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-947"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.1016\/j.jprot.2012.02.008","article-title":"Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine synovial fluid proteomics","volume":"75","author":"Chiaradia","year":"2012","journal-title":"J. Proteom."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103370","DOI":"10.1016\/j.jprot.2019.04.020","article-title":"The synovial fluid proteome differentiates between septic and nonseptic articular pathologies","volume":"202","author":"Anderson","year":"2019","journal-title":"J. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40634-014-0008-7","article-title":"The role of aggrecan in normal and osteoarthritic cartilage","volume":"1","author":"Roughley","year":"2014","journal-title":"J. Exp. Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1007\/s00264-013-1937-y","article-title":"Abnormal expression of chondroitin sulphate N-Acetylgalactosaminyltransferase 1 and Hapln-1 in cartilage with Kashin-Beck disease and primary osteoarthritis","volume":"37","author":"Zheng","year":"2013","journal-title":"Int. Orthop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.matbio.2004.07.007","article-title":"Altered patterns and synthesis of extracellular matrix macromolecules in early osteoarthritis","volume":"23","author":"Lorenzo","year":"2004","journal-title":"Matrix Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R107","DOI":"10.1186\/ar2311","article-title":"SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis","volume":"9","author":"Tew","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/jor.20602","article-title":"Chondrocytes harvested from osteochondritis dissecans cartilage are able to undergo limited in vitro chondrogenesis despite having perturbations of cell phenotype in vivo","volume":"26","author":"Garvican","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1090-0233(05)80008-5","article-title":"Equine dyschondroplasia (osteochondrosis)\u2014Histological findings and type VI collagen localization","volume":"154","author":"Henson","year":"1997","journal-title":"Vet. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.tvjl.2012.04.023","article-title":"Gene and protein expression of cartilage canal and osteochondral junction chondrocytes and full-thickness cartilage in early equine osteochondrosis","volume":"194","author":"Riddick","year":"2012","journal-title":"Vet. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.matbio.2014.08.009","article-title":"The structure and function of the pericellular matrix of articular cartilage","volume":"39","author":"Wilusz","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1002\/art.39034","article-title":"Type VI collagen regulates pericellular matrix properties, chondrocyte swelling, and mechanotransduction in mouse articular cartilage","volume":"67","author":"Zelenski","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.matbio.2018.05.008","article-title":"Osteoarthritis as a disease of the cartilage pericellular matrix","volume":"71\u201372","author":"Guilak","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1365-2613.2008.00625.x","article-title":"Involvement of the cytoskeletal elements in articular cartilage homeostasis and pathology","volume":"90","author":"Blain","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chahine, N.O., Blanchette, C., Thomas, C.B., Lu, J., and Haudenschild, D. (2013). Effect of Age and Cytoskeletal Elements on the Indentation-Dependent Mechanical Properties of Chondrocytes. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061651"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jcp.21110","article-title":"Regulation of chondrocyte differentiation by the act in cytoskeleton and adhesive interactions","volume":"213","author":"Woods","year":"2007","journal-title":"J. Cell. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/jcb.22419","article-title":"The intermediate filament vimentin regulates chondrogenesis of adult human bone marrow-derived multipotent progenitor cells","volume":"109","author":"Bobick","year":"2010","journal-title":"J. Cell. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbrc.2015.11.083","article-title":"Effects of vimentin disruption on the mechanoresponses of articular chondrocyte","volume":"469","author":"Chen","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1097\/CORR.0000000000000712","article-title":"Development and Characterization of a Novel Bipedal Standing Mouse Model of Intervertebral Disc and Facet Joint Degeneration","volume":"477","author":"Ao","year":"2019","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1002\/jcp.25500","article-title":"Cytoskeleton Aberrations in Alkaptonuric Chondrocytes","volume":"232","author":"Geminiani","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.3760\/cma.j.issn.0366-6999.20140337","article-title":"Effect of the disruption of three cytoskeleton components on chondrocyte metabolism in rabbit knee cartilage","volume":"127","author":"Duan","year":"2014","journal-title":"Chin. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1073\/pnas.1019469108","article-title":"The three-dimensional molecular structure of the desmosomal plaque","volume":"108","author":"Devos","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gao, Y., Liu, S., Huang, J., Guo, W., Chen, J., Zhang, L., Zhao, B., Peng, J., Wang, A., and Wang, Y. (2014). The ECM-cell interaction of cartilage extracellular matrix on chondrocytes. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/648459"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/j.1600-0854.2004.00210.x","article-title":"Annexin-Actin interactions","volume":"5","author":"Hayes","year":"2004","journal-title":"Traffic"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1002\/jcp.24032","article-title":"Annexin A1: Novel roles in skeletal muscle biology","volume":"227","author":"Bizzarro","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1096\/fj.06-7464rev","article-title":"Annexin 1: The new face of an old molecule","volume":"21","author":"Lim","year":"2007","journal-title":"FASEB J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"576","DOI":"10.2741\/1553","article-title":"Annexins\u2014Their role in cartilage mineralization","volume":"10","author":"Kirsch","year":"2005","journal-title":"Front. Biosci."},{"key":"ref_42","first-page":"1528","article-title":"14-3-3 Proteins and regulation of cytoskeleton","volume":"75","author":"Sluchanko","year":"2010","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"R140","DOI":"10.1152\/ajpregu.00134.2011","article-title":"Hsp90 and angiogenesis in bone disorders-lessons from the avian growth plate","volume":"301","author":"Herzog","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1002\/jcp.24923","article-title":"Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis","volume":"230","author":"Zhu","year":"2015","journal-title":"J. Cell. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hughes, A., Oxford, A.E., Tawara, K., Jorcyk, C.L., and Oxford, J.T. (2017). Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030665"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.biochi.2019.06.017","article-title":"Implication of homocysteine in protein quality control processes","volume":"165","author":"Reddy","year":"2019","journal-title":"Biochimie"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbrc.2004.08.173","article-title":"Under-sulfation by PAPS synthetase inhibition modulates the expression of ECM molecules during chondrogenesis","volume":"323","author":"Cho","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1042\/BJ20060566","article-title":"In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation","volume":"398","author":"Pecora","year":"2006","journal-title":"Biochem. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1089\/act.2009.15404","article-title":"Nutritional Supplementation for Osteoarthritis","volume":"15","author":"Ursini","year":"2009","journal-title":"Altern. Complement. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/bph.12434","article-title":"Methionine down-regulates TLR4\/MyD88\/NF-\u03baB signalling in osteoclast precursors to reduce bone loss during osteoporosis","volume":"171","author":"Vijayan","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1089\/ars.2017.7237","article-title":"Mammalian Sulfur Amino Acid Metabolism: A Nexus Between Redox Regulation, Nutrition, Epigenetics, and Detoxification","volume":"29","author":"Pajares","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biochi.2016.04.009","article-title":"One carbon metabolism and bone homeostasis and remodeling: A review of experimental research and population studies","volume":"126","author":"Feigerlova","year":"2016","journal-title":"Biochimie"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s11914-019-00506-0","article-title":"The Emerging Role of Glucose Metabolism in Cartilage Development","volume":"17","author":"Hollander","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.bonr.2018.06.003","article-title":"Expression of pro-apoptotic markers is increased along the osteochondral junction in naturally occurring osteochondrosis","volume":"9","author":"Semevolos","year":"2018","journal-title":"Bone Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/jcb.23025","article-title":"The presence of extracellular matrix alters the chondrocyte response to endoplasmic reticulum stress","volume":"112","author":"Nugent","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1089\/ten.tea.2010.0601","article-title":"The protective role of the pericellular matrix in chondrocyte apoptosis","volume":"17","author":"Peters","year":"2011","journal-title":"Tissue Eng. Part A"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.mam.2010.03.002","article-title":"VDAC, A multi-functional mitochondrial protein regulating cell life and death","volume":"31","author":"Zweckstetter","year":"2010","journal-title":"Mol. Asp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1111\/brv.12311","article-title":"Mitochondrial VDAC2 and cell homeostasis: Highlighting hidden structural features and unique functionalities","volume":"92","author":"Maurya","year":"2017","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.vaa.2016.04.004","article-title":"Effects of xylazine and dexmedetomidine on equine articular chondrocytes in vitro","volume":"44","author":"Mancini","year":"2017","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2856","DOI":"10.1038\/nprot.2006.468","article-title":"In-gel digestion for mass spectrometric characterization of proteins and proteomes","volume":"1","author":"Shevchenko","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1002\/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2","article-title":"Probability-based protein identification by searching sequence databases using mass spectrometry data","volume":"20","author":"Perkins","year":"1999","journal-title":"ELECTROPHORESIS Int. J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jprot.2013.03.017","article-title":"Ovine subclinical mastitis: Proteomic analysis of whey and milk fat globules unveils putative diagnostic biomarkers in milk","volume":"83","author":"Chiaradia","year":"2013","journal-title":"J. Proteom."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/bioinformatics\/btt019","article-title":"CluePedia Cytoscape plugin: Pathway insights using integrated experimental and in silico data","volume":"29","author":"Bindea","year":"2013","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/24\/6179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:18Z","timestamp":1760190018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/24\/6179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,7]]},"references-count":64,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ijms20246179"],"URL":"https:\/\/doi.org\/10.3390\/ijms20246179","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,7]]}}}