Network inference of pal-1 lineage-specific regulation in the C. elegans embryo by structural equation modeling

The elucidation of spatial and temporal control during developmental stages is one of the central tasks for systems biology, and a variety of intracellular factors are known as regulators for specific gene expression. The activity information of those various factors is not directly reflected in their gene expression profiles. Hence, a method based on Structural Equation Modeling (SEM) is described. SEM can include the latent variables within the constructed model and infer the relationships among latent and observed variables, as a network model. An improved SEM approach for the construction of an optimal model is applied to infer the regulatory network for the determination of C lineage fate in C. elegans development. The inferred network model shows that the 13 analysed transcription factor genes were regulated by several other factors in addition to pal-1 expression. The other regulatory factors are those involved in protein accumulation and localization as important regulatory factors for normal development. Those regulatory factors were regulated sequentially in the network model. The regulation of the known pal-1 regulated genes was dependent on this sequential control of the regulatory factors. The interpretation of the network model shows insights to the complex regulation occurring during the C lineage determination by pal-1.