Preponderance of generalized chain functions in reconstructed Boolean models of biological networks

Abstract

Abstract Boolean networks (BNs) have been extensively used to model gene regulatory networks (GRNs). The dynamics of BNs depend on the network architecture and regulatory logic rules (Boolean functions (BFs)) associated with nodes. Nested canalyzing functions (NCFs) have been shown to be enriched among the BFs in the large-scale studies of reconstructed Boolean models. The central question we address here is whether that enrichment is due to certain sub-types of NCFs. We build on one sub-type of NCFs, the chain functions (or chain-0 functions) proposed by Gat-Viks and Shamir. First, we propose two other sub-types of NCFs, namely, the class of chain-1 functions and generalized chain functions, the union of the chain-0 and chain-1 types. Next, we find that the fraction of NCFs that are chain-0 (also holds for chain-1) functions decreases exponentially with the number of inputs. We provide analytical treatment for this and other observations on BFs. Then, by analyzing three different datasets of reconstructed Boolean models we find that generalized chain functions are significantly enriched within the NCFs. Lastly we illustrate that upon imposing the constraints of generalized chain functions on three different GRNs we are able to obtain biologically viable Boolean models.

Keywords

• Gene regulatory networks
• Boolean networks
• Update rules
• Chain function
• Nested canalyzing function
• Relative enrichment