Abstract
Biological systems are by nature multiscale, consisting of subsystems that factor into progressively smaller units in a deeply hierarchical structure. At any level of the hierarchy, an ever-increasing diversity of technologies can be applied to characterize the corresponding biological units and their relations, resulting in large networks of physical or functional proximities-e.g., proximities of amino acids within a protein, of proteins within a complex, or of cell types within a tissue. Here, we review general concepts and progress in using network proximity measures as a basis for creation of multiscale hierarchical maps of biological systems. We discuss the functionalization of these maps to create predictive models, including those useful in translation of genotype to phenotype, along with strategies for model visualization and challenges faced by multiscale modeling in the near future. Collectively, these approaches enable a unified hierarchical approach to biological data, with application from the molecular to the macroscopic.