Master regulators of biological systems in higher dimensions

Area of Science:

• Genomics
• Ecology
• Evolutionary Biology

Background:

• Identifying critical genes and species is a key biological goal.
• Network analysis has identified keystone species and master regulators, but focused on pairwise interactions.
• Higher-order interactions, influenced by genetic background and species presence, remain understudied.

Purpose of the Study:

• To develop a method for studying higher-order interactions in biological networks.
• To identify key genes and species that regulate these complex interactions.
• To understand how these regulators influence evolutionary and ecological diversification.

Main Methods:

• Applied a high-dimensional geometry approach to quantify epistasis in a fitness landscape.
• Utilized 5-dimensional datasets, including genetic and microbiome data.
• Analyzed how individual genes and species influence interactions within the broader biological network.

Main Results:

• Identified specific genes (e.g., rbs locus, pykF) and species (e.g., Lactobacilli) as critical regulators.
• Demonstrated that these higher-order master regulators control numerous interactions.
• Showed these regulators influence the topography of the fitness landscape.

Conclusions:

• Provided a novel method and mathematical framework for exploring higher-dimensional biological networks.
• Highlighted the role of higher-order master regulators in driving evolutionary and ecological diversification.
• Emphasized the importance of studying complex, multi-dimensional biological interactions.