Master regulators of biological systems in higher dimensions.
Proc Natl Acad Sci U S A
; 120(51): e2300634120, 2023 Dec 19.
Article
em En
| MEDLINE
| ID: mdl-38096409
ABSTRACT
A longstanding goal of biology is to identify the key genes and species that critically impact evolution, ecology, and health. Network analysis has revealed keystone species that regulate ecosystems and master regulators that regulate cellular genetic networks. Yet these studies have focused on pairwise biological interactions, which can be affected by the context of genetic background and other species present, generating higher-order interactions. The important regulators of higher-order interactions are unstudied. To address this, we applied a high-dimensional geometry approach that quantifies epistasis in a fitness landscape to ask how individual genes and species influence the interactions in the rest of the biological network. We then generated and also reanalyzed 5-dimensional datasets (two genetic, two microbiome). We identified key genes (e.g., the rbs locus and pykF) and species (e.g., Lactobacilli) that control the interactions of many other genes and species. These higher-order master regulators can induce or suppress evolutionary and ecological diversification by controlling the topography of the fitness landscape. Thus, we provide a method and mathematical justification for exploration of biological networks in higher dimensions.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microbiota
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article