{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:37:26Z","timestamp":1770817046413,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009450","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program, National Center for Advancing Translational Sciences, National Institutes of Health","award":["Z01-TR000249"],"award-info":[{"award-number":["Z01-TR000249"]}]},{"name":"Intramural Research Program, National Cancer Institute, National Institutes of Health","award":["Z01-BC006161"],"award-info":[{"award-number":["Z01-BC006161"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Understanding relationships between spontaneous cancer in companion (pet) canines and humans can facilitate biomarker and drug development in both species. Towards this end we developed an experimental-bioinformatic protocol that analyzes canine transcriptomics data in the context of existing human data to evaluate comparative relevance of canine to human cancer. We used this protocol to characterize five canine cancers: melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, in 60 dogs. We applied an unsupervised, iterative clustering method that yielded five co-expression modules and found that each cancer exhibited a unique module expression profile. We constructed cancer models based on the co-expression modules and used the models to successfully classify the canine data. These canine-derived models also successfully classified human tumors representing the same cancers, indicating shared cancer biology between canines and humans. Annotation of the module genes identified cancer specific pathways relevant to cells-of-origin and tumor biology. For example, annotations associated with melanin production (<jats:italic>PMEL<\/jats:italic>,<jats:italic>GPNMB<\/jats:italic>, and<jats:italic>BACE2<\/jats:italic>), synthesis of bone material (<jats:italic>COL5A2<\/jats:italic>,<jats:italic>COL6A3<\/jats:italic>, and<jats:italic>COL12A1<\/jats:italic>), synthesis of pulmonary surfactant (<jats:italic>CTSH<\/jats:italic>,<jats:italic>LPCAT1<\/jats:italic>, and<jats:italic>NAPSA<\/jats:italic>), ribosomal proteins (<jats:italic>RPL8<\/jats:italic>,<jats:italic>RPS7<\/jats:italic>, and<jats:italic>RPLP0<\/jats:italic>), and epigenetic regulation (<jats:italic>EDEM1<\/jats:italic>,<jats:italic>PTK2B<\/jats:italic>, and<jats:italic>JAK1<\/jats:italic>) were unique to melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, respectively. In total, 152 biomarker candidates were selected from highly expressing modules for each cancer type. Many of these biomarker candidates are under-explored as drug discovery targets and warrant further study. The demonstrated transferability of classification models from canines to humans enforces the idea that tumor biology, biomarker targets, and associated therapeutics, discovered in canines, may translate to human medicine.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1009450","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T19:45:27Z","timestamp":1632771927000},"page":"e1009450","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5573-308X","authenticated-orcid":true,"given":"Gregory 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