4.7 Article

Biological interacting units identified in human protein networks reveal tissue-functional diversification and its impact on disease

期刊

出版社

ELSEVIER
DOI: 10.1016/j.csbj.2022.07.006

关键词

Biological function; Disease gene; Housekeeping gene; PPI network; Protein module; Tissue-specific gene

资金

  1. FCT, Portugal [UIDB/04046/2020, UIDP/04046/2020]
  2. BioSys-PhD programme from FCT (Portugal) [PD/BD/128109/2016]
  3. Instituto de Salud Carlos III (ISCiii, Spanish Ministerio de Salud) [AC14/00024, PI18/00591]
  4. Fondo Europeo de Desarrollo Regional (FEDER)
  5. France, Agence Nationale de la Recherche
  6. Germany, Bundesministerium fur Bildung und Forschung (BMBF, FKZ)
  7. Portugal, Fundacao para a Ciencia e a Tecnologia
  8. Spain, Instituto de Salud Carlos III (ISCIII)

向作者/读者索取更多资源

The centrality measures of individual proteins are insufficient to dissect the functional properties of cells, a more comprehensive, relational and context-specific method is needed. The study reveals tissue-specific functional diversification based on the identification of specific protein units.
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. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据