Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.

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...

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Autores principales:	Gregory J Tawa, John Braisted, David Gerhold, Gurmit Grewal, Christina Mazcko, Matthew Breen, Gurusingham Sittampalam, Amy K LeBlanc
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9b7d164b0c364d229d707bfd67b2595b
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spelling	oai:doaj.org-article:9b7d164b0c364d229d707bfd67b2595b2021-12-02T19:58:13ZTranscriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.1553-734X1553-735810.1371/journal.pcbi.1009450https://doaj.org/article/9b7d164b0c364d229d707bfd67b2595b2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009450https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Understanding 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 (PMEL, GPNMB, and BACE2), synthesis of bone material (COL5A2, COL6A3, and COL12A1), synthesis of pulmonary surfactant (CTSH, LPCAT1, and NAPSA), ribosomal proteins (RPL8, RPS7, and RPLP0), and epigenetic regulation (EDEM1, PTK2B, and JAK1) 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.Gregory J TawaJohn BraistedDavid GerholdGurmit GrewalChristina MazckoMatthew BreenGurusingham SittampalamAmy K LeBlancPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009450 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Gregory J Tawa John Braisted David Gerhold Gurmit Grewal Christina Mazcko Matthew Breen Gurusingham Sittampalam Amy K LeBlanc Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
description	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 (PMEL, GPNMB, and BACE2), synthesis of bone material (COL5A2, COL6A3, and COL12A1), synthesis of pulmonary surfactant (CTSH, LPCAT1, and NAPSA), ribosomal proteins (RPL8, RPS7, and RPLP0), and epigenetic regulation (EDEM1, PTK2B, and JAK1) 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.
format	article
author	Gregory J Tawa John Braisted David Gerhold Gurmit Grewal Christina Mazcko Matthew Breen Gurusingham Sittampalam Amy K LeBlanc
author_facet	Gregory J Tawa John Braisted David Gerhold Gurmit Grewal Christina Mazcko Matthew Breen Gurusingham Sittampalam Amy K LeBlanc
author_sort	Gregory J Tawa
title	Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
title_short	Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
title_full	Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
title_fullStr	Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
title_full_unstemmed	Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
title_sort	transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9b7d164b0c364d229d707bfd67b2595b
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Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species.

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