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Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space

GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. Ho...

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Main Authors: Lee, Taeheon, Lee, Sangseon, Kang, Minji, Kim, Sun
Format: Online Article Text
Language:English
Published: Nature Publishing Group UK 2021
Subjects:
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100104/
https://www.ncbi.nlm.nih.gov/pubmed/33953216
http://dx.doi.org/10.1038/s41598-021-88623-8
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author Lee, Taeheon
Lee, Sangseon
Kang, Minji
Kim, Sun
author_facet Lee, Taeheon
Lee, Sangseon
Kang, Minji
Kim, Sun
author_sort Lee, Taeheon
collection PubMed
description GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. However, modeling of GPCR families has been performed separately for each of the family, subfamily, and sub-subfamily level. Relationships between GPCR proteins are ignored in these approaches as they process the information in the proteins with several disconnected models. In this study, we propose DeepHier, a deep learning model to simultaneously learn representations of GPCR family hierarchy from the protein sequences with a unified single model. Novel loss term based on metric learning is introduced to incorporate hierarchical relations between proteins. We tested our approach using a public GPCR sequence dataset. Metric distances in the deep feature space corresponded to the hierarchical family relation between GPCR proteins. Furthermore, we demonstrated that further downstream tasks, like phylogenetic reconstruction and motif discovery, are feasible in the constructed embedding space. These results show that hierarchical relations between sequences were successfully captured in both of technical and biological aspects.
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spelling pubmed-81001042021-05-07 Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space Lee, Taeheon Lee, Sangseon Kang, Minji Kim, Sun Sci Rep Article GPCR proteins belong to diverse families of proteins that are defined at multiple hierarchical levels. Inspecting relationships between GPCR proteins on the hierarchical structure is important, since characteristics of the protein can be inferred from proteins in similar hierarchical information. However, modeling of GPCR families has been performed separately for each of the family, subfamily, and sub-subfamily level. Relationships between GPCR proteins are ignored in these approaches as they process the information in the proteins with several disconnected models. In this study, we propose DeepHier, a deep learning model to simultaneously learn representations of GPCR family hierarchy from the protein sequences with a unified single model. Novel loss term based on metric learning is introduced to incorporate hierarchical relations between proteins. We tested our approach using a public GPCR sequence dataset. Metric distances in the deep feature space corresponded to the hierarchical family relation between GPCR proteins. Furthermore, we demonstrated that further downstream tasks, like phylogenetic reconstruction and motif discovery, are feasible in the constructed embedding space. These results show that hierarchical relations between sequences were successfully captured in both of technical and biological aspects. Nature Publishing Group UK 2021-05-05 /pmc/articles/PMC8100104/ /pubmed/33953216 http://dx.doi.org/10.1038/s41598-021-88623-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Taeheon
Lee, Sangseon
Kang, Minji
Kim, Sun
Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title_full Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title_fullStr Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title_full_unstemmed Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title_short Deep hierarchical embedding for simultaneous modeling of GPCR proteins in a unified metric space
title_sort deep hierarchical embedding for simultaneous modeling of gpcr proteins in a unified metric space
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100104/
https://www.ncbi.nlm.nih.gov/pubmed/33953216
http://dx.doi.org/10.1038/s41598-021-88623-8
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