Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease
Protein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular networks are dynamic and proteins display varying...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022002860 |
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| author | Marina L. García-Vaquero Margarida Gama-Carvalho Francisco R. Pinto Javier De Las Rivas |
| author_facet | Marina L. García-Vaquero Margarida Gama-Carvalho Francisco R. Pinto Javier De Las Rivas |
| author_sort | Marina L. García-Vaquero |
| collection | DOAJ |
| description | Protein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular networks are dynamic and proteins display varying roles depending on the tissue-interactomic context. Thus, the use of centrality measures in individual proteins fall short to dissect the functional properties of the cell. For this reason, there is a need for more comprehensive, relational, and context-specific ways to analyze the multiple actions of proteins in different cells and identify specific functional assemblies within global biomolecular networks. Under this framework, we define Biological Interacting units (BioInt-U) as groups of proteins that interact physically and are enriched in a common Gene Ontology. A search strategy was applied on 33 tissue-specific (TS) PPI networks to generate BioInt libraries associated with each particular human tissue. The cross-tissue comparison showed that housekeeping assemblies incorporate different proteins and exhibit distinct network properties depending on the tissue. Furthermore, disease genes (DGs) of tissue-associated pathologies preferentially accumulate in units in the expected tissues, which in turn were more central in the TS networks. Overall, the study reveals a tissue-specific functional diversification based on the identification of specific protein units and suggests vulnerabilities specific of each tissue network, which can be applied to refine protein-disease association methods. |
| first_indexed | 2024-04-11T05:19:08Z |
| format | Article |
| id | doaj.art-0d77ba9b8cfa4fa9a73d000057d26ecf |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:08Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-0d77ba9b8cfa4fa9a73d000057d26ecf2022-12-24T04:53:21ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012037643778Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on diseaseMarina L. García-Vaquero0Margarida Gama-Carvalho1Francisco R. Pinto2Javier De Las Rivas3University of Lisboa, Faculty of Sciences, BioISI – Biosystems & Integrative Sciences Institute, Campo Grande, C8 bdg, Lisboa 1749-016, Portugal; Cancer Research Center (CiC-IBMCC, CSIC/USAL and IBSAL), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL) and Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca 37007, Spain; Corresponding author at: University of Lisboa, Faculty of Sciences, BioISI – Biosystems & Integrative Sciences Institute, Campo Grande, C8 bdg, Lisboa 1749-016, Portugal.University of Lisboa, Faculty of Sciences, BioISI – Biosystems & Integrative Sciences Institute, Campo Grande, C8 bdg, Lisboa 1749-016, PortugalUniversity of Lisboa, Faculty of Sciences, BioISI – Biosystems & Integrative Sciences Institute, Campo Grande, C8 bdg, Lisboa 1749-016, PortugalCancer Research Center (CiC-IBMCC, CSIC/USAL and IBSAL), Consejo Superior de Investigaciones Científicas (CSIC), University of Salamanca (USAL) and Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca 37007, SpainProtein-protein interactions (PPI) play an essential role in the biological processes that occur in the cell. Therefore, the dissection of PPI networks becomes decisive to model functional coordination and predict pathological de-regulation. Cellular networks are dynamic and proteins display varying roles depending on the tissue-interactomic context. Thus, the use of centrality measures in individual proteins fall short to dissect the functional properties of the cell. For this reason, there is a need for more comprehensive, relational, and context-specific ways to analyze the multiple actions of proteins in different cells and identify specific functional assemblies within global biomolecular networks. Under this framework, we define Biological Interacting units (BioInt-U) as groups of proteins that interact physically and are enriched in a common Gene Ontology. A search strategy was applied on 33 tissue-specific (TS) PPI networks to generate BioInt libraries associated with each particular human tissue. The cross-tissue comparison showed that housekeeping assemblies incorporate different proteins and exhibit distinct network properties depending on the tissue. Furthermore, disease genes (DGs) of tissue-associated pathologies preferentially accumulate in units in the expected tissues, which in turn were more central in the TS networks. Overall, the study reveals a tissue-specific functional diversification based on the identification of specific protein units and suggests vulnerabilities specific of each tissue network, which can be applied to refine protein-disease association methods.http://www.sciencedirect.com/science/article/pii/S2001037022002860Biological functionDisease geneHousekeeping genePPI networkProtein moduleTissue-specific gene |
| spellingShingle | Marina L. García-Vaquero Margarida Gama-Carvalho Francisco R. Pinto Javier De Las Rivas Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease Computational and Structural Biotechnology Journal Biological function Disease gene Housekeeping gene PPI network Protein module Tissue-specific gene |
| title | Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease |
| title_full | Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease |
| title_fullStr | Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease |
| title_full_unstemmed | Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease |
| title_short | Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease |
| title_sort | biological interacting units identified in human protein networks reveal tissue functional diversification and its impact on disease |
| topic | Biological function Disease gene Housekeeping gene PPI network Protein module Tissue-specific gene |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022002860 |
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