Longitudinal network theory approaches identify crucial factors affecting sporulation efficiency in yeast

Abstract

Integrating network theory approaches over longitudinal genome-wide gene expression data is a robust approach to understand the molecular underpinnings of a dynamic biological process. Here, we performed a network-based investigation of longitudinal gene expression changes during sporulation of a yeast strain, SK1. Using global network attributes, viz.clustering coefficient, degree distribution of a node, degree-degree mixing of the connected nodes and disassortativity, we observed dynamic changes in these parameters indicating a highly connected network with inter-module crosstalk. Analysis of local attributes, such as clustering coefficient, hierarchy, betweenness centrality and Granovetter's weak ties showed that there was an inherent hierarchy under regulatory control that was determined by specific nodes. Biological annotation of these nodes indicated the role of specifically linked pairs of genes in meiosis. These genes act as crucial regulators of sporulation in the highly sporulating SK1 strain. An independent analysis of these network properties in a less efficient sporulating strain helped to understand the heterogeneity of network profiles. We show that comparison of network properties has the potential to identify candidate nodes contributing to the phenotypic diversity of developmental processes in natural populations. Therefore, studying these network parameters as described in this work for dynamic developmental processes, such as sporulation in yeast and eventually in disease progression in humans, can help in identifying candidate factors which are potential regulators of differences between normal and perturbed processes and can be causal targets for intervention.