Biological Regulatory Networks are Minimally Frustrated

TL;DR

This study reveals that biological regulatory networks are characterized by minimal frustration, a property that supports robust cell type establishment and fate regulation, distinguishing them from random networks and offering insights into disease mechanisms.

Contribution

We identify minimal frustration as a key functional property of biological networks using Boolean modeling and spin glass concepts, highlighting its evolutionary emergence and role in cell regulation.

Findings

Biological networks exhibit minimal frustration compared to random networks.

Minimal frustration supports robust cell fate determination.

Disruption of this property may lead to diseases like cancer.

Abstract

Characterization of the differences between biological and random networks can reveal the design principles that enable the robust realization of crucial biological functions including the establishment of different cell types. Previous studies, focusing on identifying topological features that are present in biological networks but not in random networks, have, however, provided few functional insights. We use a Boolean modeling framework and ideas from spin glass literature to identify functional differences between five real biological networks and random networks with similar topological features. We show that minimal frustration is a fundamental property that allows biological networks to robustly establish cell types and regulate cell fate choice, and this property can emerge in complex networks via Darwinian evolution. The study also provides clues regarding how the regulation of cell fate choice can go awry in a disease like cancer and lead to the emergence of aberrant cell types.