Biology relies on the central thesis that the genes in an organism encode molecular mechanisms that combine with stimuli and raw materials from the environment to create a final phenotypic expression representative of the genomic programming. While conceptually simple, the genotype-to-phenotype linkage in a eukaryotic organism relies on the interactions of thousands of genes and an environment with a potentially unknowable level of complexity. Modern biology has moved to the use of networks in systems biology to try to simplify this complexity to decode how an organism's genome works. Previously, biological networks were basic ways to organize, simplify, and analyze data. However, recent advances are allowing networks to move beyond description and become phenotypes or hypotheses in their own right. This review discusses these efforts, like mapping responses across biological scales, including relationships among cellular entities, and the direct use of networks as traits or hypotheses. Biological Networks The modern molecular synthesis proposes that the genes in an organism encode molecular mechanisms that combine with signals and raw materials from the environment to create the final phenotypic expression. This genotype-to-phenotype linkage is conceptually simple, but in reality a eukaryotic organism has thousands of genes and the environment has an unknown and potentially unknowable level of complexity. This complexity has led to current efforts to utilize systems analysis to decode how an organism's genome works to create the optimal phenotype for a given environment. One simplification in the systems biology toolkit is to use biological networks to organize, simplify, and analyze data. These networks can be used to map responses across biological scales, including relationships among cellular entities, such as protein-protein interactions, gene-gene coexpression, and protein:DNA binding. The description of biological processes with networks has uncovered regulatory factors that exert control over many biological processes [1-3], regulatory motifs that shed light on signal transduction [4-7], and putative roles for genes of unknown function [8-10]. The construction of gene regulatory networks (GRNs) provides insight about the regulationdirect, indirect, or hierarchicalin a network by layering DNA-binding data (predicted or observed) onto coexpression networks. However, the predominant use of biological networks has been to describe relationships among molecules at a snapshot in time or to focus on the potential role of hub genes, yielding important insights but with significant limitations [4]. For example, downstream functional analysis of hub genes identified by network analysis can result in no obvious physiological phenotype, potentially due to functional redundancy, or the network may not translate to another experiment [11]. While some of this difficulty is caused by the available data being limiting for complete network inference, there is a key need to improve our ability to derive functional and pred...