The structure of gene-gene networks beyond pairwise interactions

TL;DR

This study investigates the complex structure of gene-gene interaction networks beyond simple pairwise connections, revealing differences in triadic interactions and network balance between essential and nonessential genes using structural balance theory.

Contribution

It applies structural balance theory to analyze triadic interactions in gene networks, uncovering differences in balance and connectivity beyond pairwise interactions.

Findings

Balanced and unbalanced triads are over and underrepresented, respectively.

Essential gene networks show more interconnected triads and different energy distributions.

Nonessential networks are more balanced when considering longer cycles.

Abstract

Despite its high and direct impact on nearly all biological processes, the underlying structure of gene-gene interaction networks is investigated so far according to pair connections. To address this, we explore the gene interaction networks of the yeast Saccharomyces cerevisiae beyond pairwise interaction using the structural balance theory (SBT). Specifically, we ask whether essential and nonessential gene interaction networks are structurally balanced. We study triadic interactions in the weighted signed undirected gene networks and observe that balanced and unbalanced triads are over and underrepresented in both networks, thus beautifully in line with the strong notion of balance. Moreover, we note that the energy distribution of triads is significantly different in both essential and nonessential networks compared with the shuffled networks. Yet, this difference is greater in the essential network regarding the frequency as well as the energy of triads. Additionally, results demonstrate that triads in the essential gene network are more interconnected through sharing common links, while in the nonessential network they tend to be isolated. Last but not least, we investigate the contribution of all-length signed walks and its impact on the degree of balance. Our findings reveal that interestingly when considering longer cycles the nonessential gene network is more balanced compared to the essential network.